80 results on '"Danafar, Hossein"'
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2. Platinum nanoparticles-embedded single-walled carbon nanotubes as a new carrier for curcumin delivery and investigating its anticancer effect on cell line 4T1.
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Mohammadi A, Bagheri F, Abutalebi Y, Aghaei A, and Danafar H
- Abstract
Cancer, a prevalent disease across various societies, presents a significant challenge in treatment research. Studies show that combination therapies are one of the methods that can help in the effective treatment of cancer. Chemotherapy and radiation therapy are among the main cancer treatments and in this project, for combined chemoradiotherapy treatment, carbon nanotubes were used as improved carriers of chemotherapy in tumors, as well as a substrate for the preparation of radiation sensitizers for local radiation therapy. Following the synthesis of CNT-Platinum-Curcumin nanoparticles (CNT-Pt-CUR), a series of analyses were conducted to verify the successful production of these nanoparticles. Techniques such as Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), UV-Vis spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), and X-Ray Diffraction (XRD) were employed. The characterization data revealed a spherical shape Pt nanoparticle morphology with an 8.5 nm diameter on rod-shape CNT, as observed through TEM. Furthermore, FTIR analysis confirmed the successful loaded of the drug into the nanoparticles, highlighting the potential of this approach in cancer treatment. Then, hemolysis and (3(-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests on normal cells were used to assess the biocompatibility of CNT-Pt-CUR nanoparticles. It also explored the anticancer efficacy of these nanoparticles at varying concentrations against cancer cells, both with and without exposure to X-rays. The research confirmed the successful synthesis of these nanoparticles and demonstrated their potential impact on cell viability. Specifically, breast cancer cells exhibited heightened susceptibility to toxicity when exposed to nanoparticles and X-rays. Further analysis revealed that the toxicity of nanoparticles is dose-dependent, and modifying the surface of carbon nanotube (CNT) nanoparticles with CUR significantly reduced blood toxicity. Interestingly, nanoparticle toxicity was significantly amplified in the presence of X-rays, suggesting mechanisms such as DNA damage and increased reactive oxygen species (ROS) levels within cells., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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3. Photothermal and radiotherapy with alginate-coated gold nanoparticles for breast cancer treatment.
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Ghaffarlou M, Rashidzadeh H, Mohammadi A, Mousazadeh N, Barsbay M, Sharafi A, Gharbavi M, Danafar H, and Javani S
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- Female, Cell Line, Tumor, Animals, Mice, Photothermal Therapy methods, Phototherapy methods, Humans, Reactive Oxygen Species metabolism, Dopamine chemistry, Cell Survival drug effects, Cell Survival radiation effects, Gold chemistry, Metal Nanoparticles chemistry, Metal Nanoparticles therapeutic use, Alginates chemistry, Breast Neoplasms radiotherapy, Breast Neoplasms drug therapy, Breast Neoplasms pathology
- Abstract
Radiation therapy and phototherapy are commonly used cancer treatments that offer advantages such as a low risk of adverse effects and the ability to target cancer cells while sparing healthy tissue. A promising strategy for cancer treatment involves using nanoparticles (NPs) in combination with radiation and photothermal therapy to target cancer cells and improve treatment efficacy. The synthesis of gold NPs (AuNPs) for use in biomedical applications has traditionally involved toxic reducing agents. Here we harnessed dopamine (DA)-conjugated alginate (Alg) for the facile and green synthesis of Au NPs (Au@Alg-DA NPs). Alg-DA conjugate reduced Au ions, simultaneously stabilized the resulting AuNPs, and prevented aggregation, resulting in particles with a narrow size distribution and improved stability. Injectable Au@Alg-DA NPs significantly promoted ROS generation in 4T1 breast cancer cells when exposed to X-rays. In addition, their administration raised the temperature under a light excitation of 808 nm, thus helping to destroy cancer cells more effectively. Importantly, no substantial cytotoxicity was detected in our Au@Alg-DA NPs. Taken together, our work provides a promising route to obtain an injectable combined radio enhancer and photothermally active nanosystem for further potential clinic translation., (© 2024. The Author(s).)
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- 2024
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4. Multi-wall carbon Nanotube surface-based functional nanoparticles for stimuli-responsive dual pharmaceutical compound delivery.
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Nabitabar M, Shaterian M, Danafar H, and Enhessari M
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- Humans, Nanoparticles chemistry, Drug Delivery Systems, Serum Albumin, Bovine chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents administration & dosage, MCF-7 Cells, Drug Carriers chemistry, Cell Survival drug effects, Cell Line, Tumor, Nanotubes, Carbon chemistry, Methotrexate chemistry, Methotrexate pharmacology, Methotrexate administration & dosage, Curcumin pharmacology, Curcumin chemistry, Curcumin administration & dosage
- Abstract
Carbon nanotubes (CNTs) have the potential to serve as delivery systems for medicinal substances and gene treatments, particularly in cancer treatment. Co-delivery of curcumin (CUR) and Methotrexate (MTX) has shown promise in cancer treatment, as it uses fewer drugs and has fewer side effects. This study used MTX-conjugated albumin (BSA)-based nanoparticles (BSA-MTX) to enhance and assess the efficiency of CUR. In-vitro cytotoxicity tests, DLS, TEM, FTIR, UV/Vis, SEM, and DSC studies assessed the formulations' physical and chemical properties. The Proteinase K enzyme was used to severe amidic linkages between MTX and BSA. The findings demonstrated the efficacy of using ƒ-MWCNT-CUR-BSA-MTX as a vehicle for efficient co-delivery of CUR and MTX in cancer treatment. The MTT colorimetric method was used to evaluate the effect of chemical and medicinal compounds. Cell division was studied using the MTT method to investigate the effect of pure MWCNT, pure CUR, MTX-BSA, and ƒ-MWCNT-CUR-MTX-BSA. Studies on cell lines have shown that the combination of curcumin and MTX with CNT can increase and improve the effectiveness of both drugs against cancer. A combination of drugs curcumin and methotrexate simultaneously had a synergistic effect on MCF-7 cells, which indicated that these drugs could potentially be used as a strategy for both prevention and treatment of breast cancer. Also, ƒ-MWCNT-CUR-MTX-BSA was found to have a significant effect on cancer treatment with minimal toxicity compared to pure curcumin, pure MTX-BSA, MTX, and ƒ-MWCNT alone. Unique properties such as a high ratio of specific surface area to volume, high chemical stability, chemical adsorption ability, high capacity of drug and biomolecules of carbon nanotubes, as well as multiple drug loading at the same time The combination of ƒ-MWCNT-CUR-BSA MTX significantly impacts cancer therapy), are desirable as an alternative option for targeted drug delivery and high therapeutic efficiency., (© 2024. The Author(s).)
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- 2024
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5. Cationic micelle delivery of a multi-epitope vaccine candidate derived from tumor-associated antigens, causing regression in established CT26 colorectal tumors in mice.
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Sabzehei F, Taromchi AH, Ramazani A, Nedaei K, Feizi A, Arsang-Jang S, and Danafar H
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- Male, Humans, Female, Animals, Mice, Epitopes, Micelles, Antigens, Neoplasm, Lymphocyte Activation, Cancer Vaccines, Colorectal Neoplasms therapy
- Abstract
Among all the cancers, colorectal cancer (CRC) has the third mortality rank in both genders. Cancer vaccines have shown promising results in boosting patients' immune systems to fight cancer. Using the IEDB database, we predicted mouse MHC-I (H2-Ld) binding epitopes from four tumor-associated antigens (APC, KRAS, TP53, and PIK3CA) and designed a multi-epitope vaccine. We expressed the candidate vaccine and encapsulated it into the cationic micelle with polyethyleneimine conjugated to oleic acid as its building blocks. We studied tumor inhibition effect, cytokine production, and lymphocyte proliferation in the mouse CRC model after vaccination. Our finding illustrated significant tumor growth inhibition in mouse models treated with the candidate nanovaccine. Besides the significant release of IFN-γ and IL-4 by immunized mouse spleen T-lymphocytes, T-cell proliferation assay results confirmed effective immune response after the vaccination. These results demonstrate the potential therapeutic effects of nanovaccines and could be a possible approach to CRC immunotherapy., (© 2023 Wiley Periodicals LLC.)
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- 2024
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6. Efficient Induction of Apoptosis in Lung Cancer Cells Using Bismuth Sulfide Nanoparticles.
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Nasehi L, Rezaeejam H, Danafar H, Mirzaghavami P, Mohammadi A, Delshad M, and Vosough M
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Background: The use of nanomaterial-based radiosensitizers to improve the therapeutic ratio has gained attraction in radiotherapy. Increased radiotoxicity applied to the tumor region may result in adverse impact on the unexposed normal cells to the radiation, a phenomenon known as radiation-induced bystander effect (RIBE)., Objectives: This study aimed to investigate the effect of Bi
2 S3 @BSA nanoparticles (NPs) as radiosensitizers on the enhancement of bystander response in non-irradiated cells., Materials and Methods: Lung carcinoma epithelial cells were exposed to 6 MV x-ray photons at different doses of 2 and 8 Gy, with and without Bi2 S3 @BSA NPs. The irradiated-cell's conditioned medium (ICCM) was collected and incubated with MCR-5 human fetal lung fibroblasts., Results: This study showed that ICCM collected from 2-Gy-irradiated A549 cells in the presence of Bi2 S3 @BSA NPs reduced the cell viability of MCR-5 bystander cells more than ICCM collected from irradiated cells without NPs ( P <0.05), whereas such a difference was not observed after 8-Gy radiation. The mRNA expression of the BAX and XPA genes, as well as the cell death rate in MCR-5 bystander cells, revealed that the Bi2 S3 @BSA NPs significantly improved bystander response at 2-Gy ( P <0.05), but the efficacy was not statistically significant after 8-Gy Irradiation., Conclusion: The results indicated that the presence of NPs did not affect bystander response enhancement at higher concentrations. These findings highlighted the potential use of radiation-enhancing agents and their benefits in radiotherapy techniques with high doses per fraction., Competing Interests: Nothing to declare., (Copyright: © 2021 The Author(s); Published by Iranian Journal of Biotechnology.)- Published
- 2024
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7. Magnetic ferrite nanoparticles coated with bovine serum albumin and glycine polymers for controlled release of curcumin as a model.
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Aghaei A, Sadiqi H, Khwaja Mohammad AA, Gulmohammad AW, Likozar B, Nosrati H, Danafar H, and Shaterian M
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- Serum Albumin, Bovine chemistry, Polymers, Delayed-Action Preparations, Drug Carriers chemistry, Magnetic Phenomena, Particle Size, Curcumin chemistry, Nanoparticles chemistry
- Abstract
To conquer the low water solubility and bioavailability of curcumin (CUR), to corroborate its functional qualities and to broaden its applicability in the pharmaceutical sector, numerous nanoscale methods have been widely exploited for its administration. Because of its polycystic, biodegradable, biocompatibility, non-toxicity, and non-allergenic properties, bovine serum albumin (BSA) and glycine (Gly) have been actively investigated as natural biopolymers for decades. Various BSA and Gly-based nanocarriers with unique features for CUR delivery, such as magnetic ferrite nanoparticles, are being developed (MNPs). In this work, magnesium ferrite (MgFe
2 O4 )/BSA and nickel ferrite (NiFe2 O4 )/Gly nanocomposites loaded with CUR (drug model) were manufactured for the first time using a chemical co-precipitation approach to create biocompatible drug nanocarriers. It was found that the synthesized MgFe2 O4 /BSA and NiFe2 O4 /Gly nanoparticles have a uniform particle distribution and their size is much less than 100 nm. Saturation magnetization in MgFe2 O4 and NiFe2 O4 reaches 13.07 and 33.4 emu/g the remarkable peak of magnetization decreases to 10.99 and 32.36 emu/g after the addition of polymers. These analyses also showed the presence of chemical bonds in the structure of the nanocomposite. The curcumin diffusion process in NPs were determined using a mathematical modeling. The yielding of the product for MgFe2 O4 /BSA and NiFe2 O4 /Gly in 200 h is about 72 and 63%, respectively. Also, regressed relative diffusivities (D/R2 ), including effective steric hindrance, were determined as 5.75 × 10-4 and 2.72 × 10-4 h-1 for MgFe2 O4 /BSA and NiFe2 O4 /Gly, respectively. It shows that there is a significant steric barrier that significantly deviates from the molecular diffusion of the liquid. As a result, the low effective release of curcumin in the particles is more noticeable. Our study demonstrated the effective relationship between the polymer architecture and the biophysical properties of the resulting nanoparticles and shed light on new approaches for the design of efficient NP-based drug carriers.- Published
- 2023
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8. Targeted co-delivery of methotrexate and chloroquine via a pH/enzyme-responsive biocompatible polymeric nanohydrogel for colorectal cancer treatment.
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Rashidzadeh H, Ramazani A, Tabatabaei Rezaei SJ, Danafar H, Rahmani S, Veisi H, Rajaeinejad M, Jamalpoor Z, and Hami Z
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- Mice, Animals, Methotrexate pharmacology, Chloroquine pharmacology, Polymers, Drug Delivery Systems methods, Hydrogen-Ion Concentration, Tumor Microenvironment, Nanoparticles, Colorectal Neoplasms drug therapy
- Abstract
Application of conventional chemotherapy regardless of its unique effectiveness have been gradually being edged aside due to limited targeting capability, lack of selectivity and chemotherapy-associated side effects. To this end, colon-targeted nanoparticles via combination therapy have shown great therapeutic potential against cancer. Herein, pH/enzyme-responsive biocompatible polymeric nanohydrogels based on poly(methacrylic acid) (PMAA) containing methotrexate (MTX) and chloroquine (CQ) were fabricated. PMAA-MTX-CQ exhibited high drug loading capacity of which MTX was 4.99% and was CQ 25.01% and displayed pH/enzyme-triggered drug release behavior. Higher CQ release rate (76%) under simulated acidic microenvironment of tumor tissue whereas 39% of CQ was released under normal physiological conditions. Intestinally, MTX release was facilitated in the presence of proteinase K enzyme. TEM image demonstrated spherical morphology with particle size of less than 50 nm. In vitro and in vivo toxicity assessments indicated that developed nanoplatforms possessed great biocompatibility. These nanohydrogels did not cause any adverse effects against Artemia Salina and HFF2 cells (around 100% cell viability) which highlight the safety of prepared nanohydrogels. There was no death in mice received different concentrations of nanohydrogel through oral administration and less than 5% hemolysis was found in red blood cells incubated with PMAA nanohydrogels. In vitro anti-cancer results showed that combination therapy based on PMAA-MTX-CQ can effectively suppress the growth of SW480 colon cancer cells (29% cell viability) compared to monotherapy. Altogether, these findings suggest that pH/enzyme-responsive PMAA-MTX-CQ could effectively inhibit cancer cell growth and progression via site-specific delivery of its cargo in a safe and controlled manner.
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- 2023
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9. Facile preparation of silver based radiosensitizers via biomineralization method for enhanced in vivo breast cancer radiotherapy.
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Ghaffarlou M, Mohammadi A, Mousazadeh N, Salehiabar M, Kalantari Y, Charmi J, Barsbay M, Ertas YN, Danafar H, Rezaeejam H, Nosrati H, and Javani S
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- Animals, Mice, Silver pharmacology, Biomineralization, Research Design, Folic Acid, Radiation-Sensitizing Agents pharmacology, Radiation Oncology, Neoplasms
- Abstract
To solve the traditional radiotherapy obstacles, and also to enhance the radiation therapy efficacy various radiosensitizers have been developed. Radiosensitizers are promising agents that under X-ray irradiation enhance injury to tumor tissue by accelerating DNA damage. In this report, silver-silver sulfide nanoparticles (Ag-Ag
2 S NPs) were synthesized via a facile, one-pot and environmentally friendly biomineralization method. Ag-Ag2 S was coated with bovine serum albumin (BSA) in situ and applied as an X-ray sensitizer to enhance the efficiency of radiotherapy. Also, folic acid (FA) was conjugated to Ag-Ag2 S@BSA to impart active targeting capability to the final formulation (Ag-Ag2 S@BSA-FA). Prepared NPs were characterized by transmission electron microscopes (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. Results show that most of the NPs have well-defined uniform Janus structures. The biocompatibility of the NPs was then evaluated both in vitro and in vivo. A series of in vitro assays were performed on 4T1 cancer cells to evaluate the therapeutic efficacy of the designed NPs. In addition, the radio-enhancing ability of the NPs was tested on the 4T1 breast cancer murine model. MTT, live and dead cell staining, apoptosis, ROS generation, and clonogenic in vitro assays demonstrated the efficacy of NPs as radiosensitizers in radiotherapy. In vivo results as well as H&E staining tumor tissues confirmed tumor destruction in the group that received Ag-Ag2 S@BSA-FA NPs and exposed to X-ray. The results showed that prepared tumor-targeted Ag-Ag2 S@BSA-FA NPs could be potential candidates as radiosensitizers for enhanced radiotherapy., (© 2023. Springer Nature Limited.)- Published
- 2023
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10. In vitro Characterization of Polyethyleneimine-Oleic Acid Cationic Micelle as a Novel Protein Carrier.
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Sabzehei F, Taromchi AH, Danafar H, Rashidzadeh H, and Ramazani A
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Background: Nanotechnology has introduced valuable carriers for vaccine delivery. The success of vaccination depends on many factors, such as the intact and safe presentation of vaccine candidates to immune cells. We have conjugated branched PEI-2k and oleic acid (OL) as the building block of the cationic micelle. We aimed to introduce a novel carrier for vaccine candidates., Materials and Methods: We conjugated polyethyleneimine and OL (POA) to synthesize the building blocks of cationic micelles. The critical micelle concentration (CMC), size and zeta potential of micelles, and their stability in 60 days were determined. Loading, encapsulation efficiency, and in vitro release study were assessed using bovine serum albumin (BSA) as a protein model. Furthermore, the cytotoxicity and hemocompatibility of developed nanosized micelles were evaluated to ascertain the biocompatibility of fabricated micelles. Cell uptake of cationic micelles in the macrophage cell line was also followed up., Results: The conjugation of two polymer parts was confirmed by Fourier transform infrared spectroscopy and
1 H nuclear magnetic resonance techniques. The CMC of the developed micelles was around 5.62 × 10-8 mg/ ml, whereas the loading and encapsulation efficiencies were 16.5% and 70%, respectively. The size and zeta potential of the cationic micelles were 96.53 ± 18.53 nm and 68.3 mV, respectively. The release of BSA from POA micelles after 8 and 72 hours was 8.5% and 82%, respectively. Finally, fluorescence microscopy showed that the prepared micelles were successfully and effectively taken up by RAW264.7 cells., Conclusion: These results may provide a cutting-edge vaccine delivery solution and open up a new avenue for future vaccine research., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)- Published
- 2023
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11. Synthesis of single-walled carbon nanotubes functionalized with platinum nanoparticles to sense breast cancer cells in 4T1 model to X-ray radiation.
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Aghaei A, Shaterian M, Danafar H, Likozar B, Šuligoj A, and Gyergyek S
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- Animals, Mice, Platinum, X-Rays, Cell Line, Serum Albumin, Bovine chemistry, Nanotubes, Carbon chemistry, Metal Nanoparticles, Neoplasms drug therapy
- Abstract
In recent years, various types of radiosensitizers have been developed to address the challenges of cancer radiotherapy. Here, platinum-functionalized oxygenated single-walled carbon nanotubes (O-SWCNTs-Pt) coated with folic acid (FA) and bovine serum albumin (BSA) (O-SWCNTs-Pt-BSA-FA) were synthesized, characterized, and used as radiosensitizers to improve the therapeutic efficacy of X-rays in a mouse model of breast cancer (4T1) in vitro. The nanosensitizer was characterized by different techniques, such as transmission electron microscopy (TEM), selected area electron diffraction (SAED), dynamic light scattering (DLS), zeta potential, X-ray diffraction (XRD), ultraviolet-visible (UV-visible), and Fourier transform infrared (FTIR) spectrometry. The evaluation of cell viability with nanocarriers O-SWCNTs-BSA, O-SWCNTs-Pt-BSA, Pt-BSA-FA, and O-SWCNTs-Pt-BSA-FA is reported at the concentrations of 10, 30, and 90 μg/mL by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the presence and absence of X-rays at 4 and 8 Gy. The results showed that administration of O-SWCNTs-BSA, O-SWCNTs-Pt-BSA, Pt-BSA-FA, and O-SWCNTs-Pt-BSA-FA + 8 Gy at a concentration of 90 μg/mL reduced survival by 75.31, 65.32, 67.35, and 60.35%, respectively. O-SWCNTs-Pt-BSA-FA has a hydrodynamic size of 88.57 nm and a surface charge of -29 mV, which indicates special stability. Compared with O-SWCNTs-BSA, O-SWCNTs-Pt-BSA, and Pt-BSA-FA, it has very strong cell-killing activity in the 4T1 cell line. It is also noteworthy that SWCNTs can act as a controlled release and delivery system for PtNPs due to their unique properties and easy penetration into biological membranes. As a result, the new nanosensitizer may play a role in cancer treatment in conjunction with radiotherapy technology. Graphical abstract., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
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- 2023
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12. Silver sulfide coated alginate radioenhancer for enhanced X-ray radiation therapy of breast cancer.
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Mousazadeh N, Seidi F, Ghaffarlou M, Rashidzadeh H, Hosseinmirzaei A, Mozafari F, Danafar H, and Nosrati H
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- Humans, Female, Alginates, X-Rays, Spectroscopy, Fourier Transform Infrared, Reactive Oxygen Species, Breast Neoplasms radiotherapy, Breast Neoplasms pathology, Metal Nanoparticles therapeutic use
- Abstract
A wide range of high-Z nanomaterials are fabricated to decrease radiation dose by sensitizing cells to irradiation through various mechanisms such as ROS generation enhancement. Alginate-coated silver sulfide nanoparticles (Ag
2 S@Alg) were synthesized and characterized by SEM, TEM, DLS, XRD, EPS, FT-IR, and UV-vis analysis techniques. Cytotoxicity of nanoparticles was tested against HFF-2, MCF-7, and 4 T1 cell lines for biocompatibility and radio enhancement ability evaluation, respectively. Moreover, the hemolysis assay demonstrated that the nanoparticles were biocompatible and nontoxic. In vitro intracellular ROS generation and calcein AM/PI co-staining unveiled cancerous cell death induction by nanoradiosensitizer, Ag2 S@Alg. Further, histopathology results emphasized the tumor ablation capability of Ag2 S@Alg. Silver anticancer properties were also recognized and combined with its radiosensitizing effect under X-ray irradiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)- Published
- 2023
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13. Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery.
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Mozafari F, Rashidzadeh H, Bijani S, Zare-Molaei F, Islambulchilar Z, Danafar H, Kalantari-Hesari A, Ramazani A, and Hosseini MJ
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- Rats, Animals, Rats, Wistar, Edaravone pharmacology, Edaravone therapeutic use, Nanogels, Brain, Glutathione, Ischemia, Antioxidants pharmacology, Antioxidants therapeutic use, Acute Disease, Neuroprotection, Ischemic Stroke
- Abstract
Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that is capable of scavenging reactive oxygen species, especially hydroxyl molecules, and has been already used for ischemic stroke treatment. However, poor water solubility, low stability, and bioavailability in aqueous media are major EDV drawbacks. Thus, to overcome the aforementioned drawbacks, nanogel was exploited as a drug carrier of EDV. Furthermore, decorating the nanogel surface with glutathione as targeting ligands would potentiate the therapeutic efficacy. Nanovehicle characterization was assessed with various analytical techniques. Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation were assessed. The outcome demonstrated a diameter of around 100 nm, sphere shape, and homogenous morphology. Encapsulation efficiency and drug loading were determined to be 99.9% and 37.5%, respectively. In vitro drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously made the possibility of antioxidant effects on the brain in specific doses, which resulted in elevated spatial memory and learning along with cognitive function in Wistar rats. In addition, significantly lower MDA and PCO and higher levels of neural GSH and antioxidant levels were observed, while histopathological improvement was approved. The developed nanogel can be a suited vehicle for drug delivery of EDV to the brain and improve ischemia-induced oxidative stress cell damage., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Faezeh Mozafari et al.)
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- 2023
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14. Synthesis of Fe 3 O 4 -Gold hybrid nanoparticles coated by bovine serum albumin as a contrast agent in MR imaging.
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Danafar H, Baghdadchi Y, Barsbay M, Ghaffarlou M, Mousazadeh N, and Mohammadi A
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Despite the over spatial separation and the ability to determine soft tissues, insufficient contrast is the shortcoming of magnetic resonance imaging (MRI) that could be circumvented by the use of contrast agents. The use of MRI contrast agents are widely applied to enhance the vision of internal body structures. Nano-sized contrast materials have unique application advantages compared to other contrast agents due to their size and shape. However, for contrast agents such as bare iron (II, III) oxide (Fe
3 O4 ) magnetic nanoparticles (NPs), aggregation and accumulation are the main shortcomings. Thus, surface modifications are necessary for their use in biopharmaceutical applications. Gold, Au, nanoparticles are of big interesting for use in biomedical purposes due to their chemical stability and oxidation resistance. In this study, we synthesized magnetic Fe3 O4 -Au hybrid NPs with a facile method and coated them with bovine serum albumin (BSA) to increase their chemical stability and biocompatibility. Afterwards, the hybrid nanosystem was characterized by some methods, and their potential to increase MRI contrast was investigated by the phantom MRI experiments. Our data showed that the signal intensity on MR images was significantly reduced, thus confirming the contrast ability of the formulated Fe3 O4 -Au-BSA NPs., Competing Interests: The authors declare no conflict of interest., (© 2023 Published by Elsevier Ltd.)- Published
- 2023
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15. Synthesis and characterization of bovine serum albumin-coated copper sulfide nanoparticles as curcumin nanocarriers.
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Mohammadi A and Danafar H
- Abstract
Cancer is among the most common causes of death in the world that affects a large number of people every year. Curcumin is one of the natural anticancer therapeutics with little or no negative effects. However, due to its hydrophobic nature, poor bioavailability, limited gastrointestinal uptake, and fast metabolism, its therapeutic applications are constrained. Therefore, the Bovine Serum Albumin-Coated Copper Sulfide anoparticles (CuS@BSA) for curcumin (CUR) drug delivery were synthesized and characterized, and then curcumin release from the nanosystem. Hemotoxicity, and cytotoxicity was investigated. This study involved the one-step synthesis of CuS@BSA nanoparticles first, followed by the addition of CUR. Then the synthesized nanoparticles were characterized employing Scanning Transient Electron Microscopy (STEM), Ultraviolet-visible spectroscopy (UV-vis) and Fourier-transform infrared spectroscopy (FT-IR) techniques. The Size and surface charge (zeta potential) of synthesized nanoparticles were determined by Dynamic Light Scattering (DLS) to be 120 nm and -13 eV, respectively. The results showed that the CUR loading was around 15% and also the release pattern of CUR was dependent on pH and increased in an acidic environment. The results of the hemolysis assay showed that the synthesized nanoparticles are not hemotoxic. The investigation of the cytotoxic effects of synthesized nanoparticles on cancer cells demonstrated that CuS@BSA nanoparticles did not exhibit any toxicity and therefore are an appropriate candidate for drug delivery., Competing Interests: The authors declare no conflict of interest., (© 2023 Published by Elsevier Ltd.)
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- 2023
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16. Targeted CuFe 2 O 4 hybrid nanoradiosensitizers for synchronous chemoradiotherapy.
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Salehiabar M, Ghaffarlou M, Mohammadi A, Mousazadeh N, Rahimi H, Abhari F, Rashidzadeh H, Nasehi L, Rezaeejam H, Barsbay M, Ertas YN, Nosrati H, Kavetskyy T, and Danafar H
- Subjects
- Mice, Animals, Drug Carriers, Chemoradiotherapy, Antineoplastic Agents therapeutic use, Curcumin, Neoplasms drug therapy, Nanoparticles
- Abstract
Multifunctional nanoplatforms based on novel bimetallic nanoparticles have emerged as effective radiosensitizers owing to their potential capability in cancer cells radiosensitization. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. Herein, a tumor targeted nanoradiosensitizer with synchronous chemoradiotion properties, termed as CuFe
2 O4 @BSA-FA-CUR, loaded with curcumin (CUR) and modified by bovine serum albumin (BSA) and folic acid (FA) was developed to enhance tumor accumulation and promote the anti-cancer activity while attenuating adverse effects. Both copper (Cu) and iron (Fe) were utilized in the construction of these submicron scale entities, therefore strong radiosensitization effect is anticipated by implementation of these two metals. The structure-function relationships between constituents of nanomaterials and their function led to the development of nanoscale materials with great radiosensitizing capacity and biosafety. BSA was used to anchor Fe and Cu ions but also to improve colloidal stability, blood circulation time, biocompatibility, and further functionalization. Moreover, to specifically target tumor sites and enhance cellular uptake, FA was conjugated onto the surface of hybrid bimetallic nanoparticles. Finally, CUR as a natural chemotherapeutic agent was encapsulated into the developed bimetallic nanoparticles. With incorporation of all abovementioned stages into one multifunctional nanoplatform, CuFe2 O4 @BSA-FA-CUR is produced for synergistic chemoradiotherapy with positive outcomes. In vitro investigation revealed that these nanoplatforms bear excellent biosafety, great tumor cell killing ability and radiosensitizing capacity. In addition, high cancer-suppression efficiency was observed through in vivo studies. It is worth mentioning that co-use of CuFe2 O4 @BSA-FA-CUR nanoplatforms and X-ray radiation led to complete tumor ablation in almost all of the treated mice. No mortality or radiation-induced normal tissue toxicity were observed following administration of CuFe2 O4 @BSA-FA-CUR nanoparticles which highlights the biosafety of these submicron scale entities. These results offer powerful evidence for the potential capability of CuFe2 O4 @BSA-FA-CUR in radiosensitization of malignant tumors and opens up a new avenue of research in this area., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2023
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17. BSA-PEI Nanoparticle Mediated Efficient Delivery of CRISPR/Cas9 into MDA-MB-231 Cells.
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Rahimi H, Zaboli KA, Thekkiniath J, Mousavi SH, Johari B, Hashemi MR, Nosrati H, Goldschneider D, Bernet A, Danafar H, and Kaboli S
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- Animals, CRISPR-Associated Protein 9 genetics, Humans, Mice, Polyethyleneimine, Ribonucleoproteins genetics, Ribonucleoproteins metabolism, Serum Albumin, Bovine, CRISPR-Cas Systems, Nanoparticles
- Abstract
The discovery of bacterial-derived Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has revolutionized genome engineering and gene therapy due to its wide range of applications. One of the major challenging issues in CRISPR/Cas system is the lack of an efficient, safe, and clinically suitable delivery of the system's components into target cells. Here, we describe the development of polyethylenimine coated-bovine serum albumin nanoparticles (BSA-PEI NPs) for efficient delivery of CRISPR/Cas9 system in both DNA (px458 plasmid) and ribonucleoprotein (RNP) forms into MDA-MB-231 human breast cancer cell line. Our data showed that synthesized BSA-PEI (BP) NPs delivered plasmid px458 at concentrations of 0.15, 0.25, and 0.35 µg/µl with efficiencies of approximately 29.7, 54.8, and 84.1% into MDA-MB-231 cells, respectively. Our study demonstrated that Cas9/sgRNA RNP complex efficiently (~ 92.6%) delivered by BSA-PEI NPs into the same cells. Analysis of toxicity and biocompatibility of synthesized NPs on human red blood cells, MDA-MB-231 cells, and mice showed that the selected concentration (28 µg/µl) of BSA-PEI NPs for transfection had no remarkable toxicity effects. Thus, obtained results suggest BSA-PEI NPs as one of the most promising carrier for delivering CRISPR/Cas9 to target cells., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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18. Bovine serum albumin-mediated synthesis and quorum sensing inhibitory properties of Ag-Ag 2 S nanoparticles.
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Ghaffarlou M, İlk S, Rahimi H, Danafar H, Barsbay M, and Sharafi A
- Subjects
- Serum Albumin, Bovine chemistry, Silver pharmacology, Silver chemistry, Anti-Bacterial Agents pharmacology, Biofilms, Quorum Sensing, Metal Nanoparticles chemistry
- Abstract
Aim: Quorum sensing (QS) is a density-dependent chemical process of cell-to-cell communication in which certain signals are activated, leading to the coordination of pathogenic behaviors and the regulation of virulence in bacteria. Inhibition of QS can prevent biofilm formation and reduce virulence behaviors of bacteria. Herein, bovine serum albumin (BSA)-coated silver nanoparticles (NPs) (Ag-Ag
2 S@BSA NPs) were synthesized and studied as an anti-QS agent. Materials & methods: Ag-Ag2 S NPs prepared through a BSA-mediated biomineralization process under ambient aqueous conditions and their physicochemical properties were characterized. The anti-QS activity of the resulting BSA-coated NPs (Ag-Ag2 S@BSA NPs) was investigated for the first time. Results & conclusion: The result confirmed the potential of Ag-Ag2 S@BSA NPs as novel and useful therapeutic tools for antibacterial purposes.- Published
- 2022
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19. Magnetite and bismuth sulfide Janus heterostructures as radiosensitizers for in vivo enhanced radiotherapy in breast cancer.
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Nosrati H, Ghaffarlou M, Salehiabar M, Mousazadeh N, Abhari F, Barsbay M, Ertas YN, Rashidzadeh H, Mohammadi A, Nasehi L, Rezaeejam H, Davaran S, Ramazani A, Conde J, and Danafar H
- Subjects
- Animals, Bismuth, Female, Ferrosoferric Oxide, Humans, Mice, Reactive Oxygen Species, Serum Albumin, Bovine chemistry, Sulfides, Breast Neoplasms drug therapy, Metal Nanoparticles therapeutic use, Radiation-Sensitizing Agents therapeutic use
- Abstract
Janus heterostructures based on bimetallic nanoparticles have emerged as effective radiosensitizers owing to their radiosensitization capabilities in cancer cells. In this context, this study aims at developing a novel bimetallic nanoradiosensitizer, Bi
2 S3 -Fe3 O4 , to enhance tumor accumulation and promote radiation-induced DNA damage while reducing adverse effects. Due to the presence of both iron oxide and bismuth sulfide metallic nanoparticles in these newly developed nanoparticle, strong radiosensitizing capacity is anticipated through the generation of reactive oxygen species (ROS) to induce DNA damage under X-Ray irradiation. To improve blood circulation time, biocompatibility, colloidal stability, and tuning surface functionalization, the surface of Bi2 S3 -Fe3 O4 bimetallic nanoparticles was coated with bovine serum albumin (BSA). Moreover, to achieve higher cellular uptake and efficient tumor site specificity, folic acid (FA) as a targeting moiety was conjugated onto the bimetallic nanoparticles, termed Bi2 S3 @BSA-Fe3 O4 -FA. Biocompatibility, safety, radiation-induced DNA damage by ROS activation and generation, and radiosensitizing ability were confirmed via in vitro and in vivo assays. The administration of Bi2 S3 @BSA-Fe3 O4 -FA in 4T1 breast cancer murine model upon X-ray radiation revealed highly effective tumor eradication without causing any mortality or severe toxicity in healthy tissues. These findings offer compelling evidence for the potential capability of Bi2 S3 @BSA-Fe3 O4 -FA as an ideal nanoparticle for radiation-induced cancer therapy and open interesting avenues of future research in this area., Competing Interests: Declaration of competing interest J.C. is a co-founder and shareholder of TargTex S.A., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2022
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20. Evaluation of PLGA nanoparticles containing outer membrane proteins of Acinetobacter baumannii bacterium in stimulating the immune system in mice.
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Gholizadeh A, Shapoury R, Pakzad P, Mahdavi M, and Danafar H
- Abstract
Background and Purpose: Acinetobacter baumannii (A. baumannii) is known as a pathogen with antibiotic resistance, causing respiratory infections. PLGA has been approved for use in vaccines as well as drug delivery. This study was performed to evaluate PLGA nanoparticles containing the outer membrane proteins (OMPs) of A. baumannii in stimulating the mice's immune system and improving pneumonia., Experimental Approach: Double emulsion solvent evaporation technique was used. The properties of the obtained nanospheres were determined using a zetasizer, FTIR, and AFM devices. Nanoparticles were administered to mice BALB/c by applying the intramuscular route. ELISA was used to measure the amounts of immunoglobulins produced; also, an opsonophagocytic killing assay was used to measure the effectiveness of immunoglobulins. Immunized mice were then challenged with live A. baumannii through the lungs; their internal organs were also removed for bacteriological studies., Findings/results: The prepared particles were 550 nm in diameter with a negative surface charge. The production of the OMPs specific IgG was much higher in the group receiving nanoparticles containing antigen as compared to those getting pure antigen. The immunoglobulins produced against nanoparticles were superior to those developed against pure antigens. Mice that received the new nanovaccine were more resistant to pneumonia caused by this bacterium than those that received pure antigen., Conclusion and Implication: Overall, it can be said that PLGA nanoparticles could deliver their internal antigens (OMPs) well to the immune system of mice and stimulate humoral immunity in these animals, thus protecting them against pneumonia caused by A. baumannii ., Competing Interests: The authors declared no conflict of interest in this study., (Copyright: © 2022 Research in Pharmaceutical Sciences.)
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- 2022
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21. Co-delivery of siRNA and lycopene encapsulated hybrid lipid nanoparticles for dual silencing of insulin-like growth factor 1 receptor in MCF-7 breast cancer cell line.
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Mennati A, Rostamizadeh K, Manjili HK, Fathi M, and Danafar H
- Subjects
- Humans, MCF-7 Cells, Female, Apoptosis drug effects, Polyethylene Glycols chemistry, Gene Silencing, Cell Proliferation drug effects, Polyesters chemistry, Insulin-Like Peptides, Liposomes, Lycopene pharmacology, Lycopene chemistry, Receptor, IGF Type 1 genetics, Nanoparticles chemistry, RNA, Small Interfering genetics, RNA, Small Interfering administration & dosage, Breast Neoplasms genetics, Breast Neoplasms drug therapy, Breast Neoplasms pathology
- Abstract
Insulin-like growth factor-1 receptor (IGF-1R) is expressed in malignant and normal breast tissue, and its intermittent activation by multiple IGF-1 signaling pathways leads to neoplasm cell proliferation, impaired apoptosis, increased survival, and resistance to cytotoxic therapeutic agents. Therefore, simultaneous suppression of the receptor and its cognate ligand would be a powerful promising strategy inhibiting malignant phenotypes of breast cancer cells. In the present study, Methoxypoly(ethylene glycol) - Poly(caprolactone) was hybridized with Dimethyldioctadecylammonium bromide (DDAB) cationic lipid (mPEG-PCL-DDAB) nanoparticles (NPs) and used as a carrier for simultaneous delivery of lycopene and insulin-like growth factor 1 receptor-specific lycopene encapsulated-mPEG-PCL-DDAB nanoparticle/siRNA to MCF-7 breast cancer cells. Then, the antitumor effects of this construct were evaluated in vitro. The results demonstrated that the synthesized mPEG-PCL-DDAB nanoparticle had suitable physicochemical properties. The use of mPEG-PCL-DDAB nanoparticle-loaded anti-insulin-like growth factor 1 receptor-siRNA and lycopene dramatically induced the process of apoptosis and arrested cell cycle in the MCF-7 tumor cell lines. In general, the findings of this study demonstrated the potency of mPEG-PCL-DDAB nanoparticles for dual delivery of siRNA, and lycopene in breast cancer cell lines followed the induction of apoptosis., (Copyright © 2021. Published by Elsevier B.V.)
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- 2022
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22. Anticancer evaluation of methotrexate and curcumin-coencapsulated niosomes against colorectal cancer cell lines.
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Mousazadeh N, Gharbavi M, Rashidzadeh H, Nosrati H, Danafar H, and Johari B
- Subjects
- Cell Line, Tumor, HCT116 Cells, Humans, Liposomes chemistry, Methotrexate chemistry, Particle Size, Antineoplastic Agents chemistry, Colorectal Neoplasms drug therapy, Curcumin chemistry
- Abstract
Aim: The aim of the present investigation was to develop niosomes containing both curcumin (CUR) and methotrexate (MTX). Also, the combinational effect of CUR and MTX in both free and niosomal forms on growth inhibition potential and induction of apoptosis in the HCT-116 cell line were exploited. Materials & methods: Niosomes were prepared by the thin-film hydration method and their physicochemical properties were determined by various techniques. Cellular uptake, cell apoptosis, wound healing and MTT assay were conducted to ascertain niosomes' feasibility for cancer therapy. Results: The combination of CUR and MTX in niosomal formulation showed more toxicity than their combination in free form. Conclusion: The nanocarrier-based approach was effective for the codelivery of CUR and MTX against cancer cells in vitro .
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- 2022
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23. Prodrug Polymeric Nanoconjugates Encapsulating Gold Nanoparticles for Enhanced X-Ray Radiation Therapy in Breast Cancer.
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Nosrati H, Seidi F, Hosseinmirzaei A, Mousazadeh N, Mohammadi A, Ghaffarlou M, Danafar H, Conde J, and Sharafi A
- Subjects
- Animals, Cell Line, Tumor, Gold, Mice, Nanoconjugates, X-Rays, Curcumin therapeutic use, Metal Nanoparticles therapeutic use, Nanoparticles, Neoplasms drug therapy, Prodrugs pharmacology
- Abstract
An optimal radiosensitizer with improved tumor retention has an important effect on tumor radiation therapy. Herein, gold nanoparticles (Au NPs) and drug-containing, mPEG-conjugated CUR (mPEG-CUR), self-assembled NPs (mPEG-CUR@Au) are developed and evaluated as a drug carrier and radiosensitizer in a breast cancer mice model. As a result, cancer therapy efficacy is improved significantly by applying all-in-one NPs to achieve synchronous chemoradiotherapy, as evidenced by studies evaluating cell viability, proliferation, and ROS production. In vivo anticancer experiments show that the mPEG-CUR@Au system improves the radiation sensitivity of 4T1 mammary carcinoma and completely abrogates breast cancer., (© 2021 Wiley-VCH GmbH.)
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- 2022
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24. Curcumin delivery by modified biosourced carbon-based nanoparticles.
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Danafar H, Salehiabar M, Barsbay M, Rahimi H, Ghaffarlou M, Arbabi Zaboli K, Faghfoori MH, Kaboli S, Nosrati H, and Faghfoori Z
- Subjects
- Drug Carriers chemistry, Humans, MCF-7 Cells, Serum Albumin, Bovine chemistry, Curcumin chemistry, Curcumin pharmacology, Nanoparticles chemistry
- Abstract
Aim: To prepare a novel hybrid system for the controlled release and delivery of curcumin (CUR). Methods: A method for the ultrasound-assisted fabrication of protein-modified nanosized graphene oxide-like carbon-based nanoparticles (CBNPs) was developed. After being modified with bovine serum albumin (BSA), CUR was loaded onto the synthesized hybrid (labeled CBNPs@BSA-CUR). The structure and properties of the synthesized nanoparticles were elucidated using transmission electron microscopy (TEM), atomic force microscopy (AFM), ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and x-ray photoelectron spectroscopy (XPS) methods. Results: CBNPs@BSA-CUR showed pH sensitivity and were calculated as controlled CUR release behavior. The drug-free system exhibited good biocompatibility and was nontoxic. However, CBNPs@BSA-CUR showed acceptable antiproliferative ability against MCF-7 breast cancer cells. Conclusion: CBNPs@BSA-CUR could be considered a highly promising nontoxic nanocarrier for the delivery of CUR with good biosafety.
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- 2022
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25. Targeted drug delivery via folate decorated nanocarriers based on linear polymer for treatment of breast cancer.
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Zamani M, Aghajanzadeh M, Sharafi A, Rostamizadeh K, and Danafar H
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- Animals, Drug Carriers chemistry, Drug Delivery Systems, Folic Acid chemistry, Mice, Micelles, Polyethylene Glycols chemistry, Polymers chemistry, Curcumin chemistry, Neoplasms drug therapy
- Abstract
In this project, a biocompatible block copolymer including poly ethylene glycol and poly caprolactone was synthesized using ring-opening reaction. Then, the copolymer was conjugated to folic acid using lysine as a linker. Also, curcumin (CUR) was used as a therapeutic anticancer agent. Nanoprecipitation method was used to prepare CUR-loaded polymeric micelles. Different methods including Fourier-transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the prepared nanocarriers (NCs). MTT assay and hemolysis assay were used to evaluate in vitro anticancer efficiency and biocompatibility of the prepared NCs, respectively. The results proved efficiency of NCs as a drug delivery system (DDS) in various aspects such as physicochemical properties and biocompatibility. Also, in vivo results showed that NCs did not show any severe weight loss and side effects on mice, and the anti-cancer study results of the CUR-loaded NCs proved that the conjugation of folic acid on the surface of NCs as a targeting agent could increase the therapeutic efficacy of CUR.
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- 2022
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26. Complete ablation of tumors using synchronous chemoradiation with bimetallic theranostic nanoparticles.
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Nosrati H, Attari E, Abhari F, Barsbay M, Ghaffarlou M, Mousazadeh N, Vaezi R, Kavetskyy T, Rezaeejam H, Webster TJ, Johari B, and Danafar H
- Abstract
Synchronous chemotherapy and radiotherapy, termed chemoradiation therapy, is now an important standard regime for synergistic cancer treatment. For such treatment, nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy. Herein, we designed a Schottky-type theranostic heterostructure, Bi
2 S3 -Au, with deep level defects (DLDs) in Bi2 S3 as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation. Methotrexate (MTX) was conjugated onto the Bi2 S3 -Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior. The designed hybrid system also contained curcumin (CUR), which cannot only serve as a nutritional supplement for chemotherapy, but also can play an important role in the radioprotection of normal cells. Impressively, this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation, completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)- Published
- 2021
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27. Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model.
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Nosrati H, Baghdadchi Y, Abbasi R, Barsbay M, Ghaffarlou M, Abhari F, Mohammadi A, Kavetskyy T, Bochani S, Rezaeejam H, Davaran S, and Danafar H
- Subjects
- Animals, Cell Line, Tumor, Chemoradiotherapy, Mice, Breast Neoplasms therapy, Ferric Compounds pharmacology, Gold pharmacology, Radiation-Sensitizing Agents pharmacology
- Abstract
The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.
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- 2021
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28. CRISPR Systems for COVID-19 Diagnosis.
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Rahimi H, Salehiabar M, Barsbay M, Ghaffarlou M, Kavetskyy T, Sharafi A, Davaran S, Chauhan SC, Danafar H, Kaboli S, Nosrati H, Yallapu MM, and Conde J
- Subjects
- COVID-19 Testing, CRISPR-Cas Systems genetics, Humans, SARS-CoV-2, COVID-19, Clustered Regularly Interspaced Short Palindromic Repeats genetics
- Abstract
The emergence of the new coronavirus 2019 (COVID-19) was first seen in December 2019, which has spread rapidly and become a global pandemic. The number of cases of COVID-19 and its associated mortality have raised serious concerns worldwide. Early diagnosis of viral infection undoubtedly allows rapid intervention, disease management, and substantial control of the rapid spread of the disease. Currently, the standard approach for COVID-19 diagnosis globally is the RT-qPCR test; however, the limited access to kits and associated reagents, the need for specialized lab equipment, and the need for highly skilled personnel has led to a detection slowdown. Recently, the development of clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostic systems has reshaped molecular diagnosis. The benefits of the CRISPR system such as speed, precision, specificity, strength, efficiency, and versatility have inspired researchers to develop CRISPR-based diagnostic and therapeutic methods. With the global COVID-19 outbreak, different groups have begun to design and develop diagnostic and therapeutic programs based on the efficient CRISPR system. CRISPR-based COVID-19 diagnostic systems have advantages such as a high detection speed (i.e., 30 min from raw sample to reach a result), high sensitivity and precision, portability, and no need for specialized laboratory equipment. Here, we review contemporary studies on the detection of COVID-19 based on the CRISPR system.
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- 2021
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29. Anti-Proliferative Properties, Biocompatibility, and Chemical Composition of Different Extracts of Plantago major Medicinal Plant.
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Rahamooz-Haghighi S, Bagheri K, Danafar H, and Sharafi A
- Subjects
- Administration, Oral, Animals, Artemia, Body Weight drug effects, Cell Death drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Ethanol, Gas Chromatography-Mass Spectrometry, HEK293 Cells, Hemolysis drug effects, Humans, Inhibitory Concentration 50, Mice, Plant Extracts toxicity, Toxicity Tests, Acute, Biocompatible Materials pharmacology, Plant Extracts chemistry, Plant Extracts pharmacology, Plantago chemistry, Plants, Medicinal chemistry
- Abstract
Background: To study the anticancer activity of Plantago major, we assessed the effect of ethanolic, methanolic and acetonic extracts of this plant on HCT-116, SW-480, and HEK-293 cell lines as control., Methods: The cytotoxic activity, biocompatibility, and toxicity were evaluated by MTT assay, hemolysis, and Artemia salina-LD50 (on mice) tests, respectively. The analysis of the extracts was performed by GC-MS analysis., Results: The results showed that all the extracts had the most antiproliferative properties on the HCT-116 cell line. The P. major root extract was more effective than the aerial parts, and IC50 values for ethanolic, methanolic and acetonic root extracts were 405.59, 470.16, and 82.26 µg/mL, respectively on HCT-116 cell line at 72 h. Hemolysis degree of the ethanolic extract of aerial and root parts were approximately 1% at 400 μg/mL.. Using the ethanolic extracts, the Artemia survived every concentration, and no toxicity was observed. One week after the oral administration of different parts of P. major extracts, none of the mice died, even those were administered 2000 mg/kg. The results of GC/MS analysis showed that P. major extracts contain potential anticancer compounds, such as stearic acid (8.61%) in aerial parts of methanolic extract and 1,2- Benzenedicarboxylic acid, mono(2-ethylhexyl)ester (88.07% and 40.63%) in aerial and root parts of acetonic extract of P. major., Conclusion: Our findings suggest that the P. major is a source of potential compounds with antiproliferative properties.
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- 2021
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30. Nanotechnology against the novel coronavirus (severe acute respiratory syndrome coronavirus 2): diagnosis, treatment, therapy and future perspectives.
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Rashidzadeh H, Danafar H, Rahimi H, Mozafari F, Salehiabar M, Rahmati MA, Rahamooz-Haghighi S, Mousazadeh N, Mohammadi A, Ertas YN, Ramazani A, Huseynova I, Khalilov R, Davaran S, Webster TJ, Kavetskyy T, Eftekhari A, Nosrati H, and Mirsaeidi M
- Subjects
- Animals, COVID-19 prevention & control, COVID-19 Testing methods, Humans, Nanostructures chemistry, Nanotechnology methods, Peptides chemistry, Peptides therapeutic use, Polymers chemistry, Polymers therapeutic use, Proteins chemistry, Proteins therapeutic use, SARS-CoV-2 isolation & purification, COVID-19 diagnosis, COVID-19 therapy, Nanomedicine methods, Nanostructures therapeutic use
- Abstract
COVID-19, as an emerging infectious disease, has caused significant mortality and morbidity along with socioeconomic impact. No effective treatment or vaccine has been approved yet for this pandemic disease. Cutting-edge tools, especially nanotechnology, should be strongly considered to tackle this virus. This review aims to propose several strategies to design and fabricate effective diagnostic and therapeutic agents against COVID-19 by the aid of nanotechnology. Polymeric, inorganic self-assembling materials and peptide-based nanoparticles are promising tools for battling COVID-19 as well as its rapid diagnosis. This review summarizes all of the exciting advances nanomaterials are making toward COVID-19 prevention, diagnosis and therapy.
- Published
- 2021
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31. Immuno-informatics analysis and expression of a novel multi-domain antigen as a vaccine candidate against glioblastoma.
- Author
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Gharbavi M, Danafar H, Amani J, and Sharafi A
- Subjects
- Brain Neoplasms immunology, Brain Neoplasms metabolism, Brain Neoplasms pathology, Cancer Vaccines genetics, Cancer Vaccines immunology, Databases, Genetic, Gene Expression Regulation, Neoplastic, Genomics, Glioblastoma immunology, Glioblastoma metabolism, Glioblastoma pathology, Humans, Immunodominant Epitopes, Immunogenicity, Vaccine, Interleukin-13 Receptor alpha2 Subunit genetics, Interleukin-13 Receptor alpha2 Subunit immunology, Molecular Docking Simulation, Protein Conformation, Receptor-Like Protein Tyrosine Phosphatases, Class 5 genetics, Receptor-Like Protein Tyrosine Phosphatases, Class 5 immunology, Structure-Activity Relationship, Tenascin genetics, Tenascin immunology, Vaccines, Synthetic therapeutic use, Brain Neoplasms drug therapy, Cancer Vaccines therapeutic use, Computational Biology, Glioblastoma drug therapy
- Abstract
Glioblastoma multiform is the most common of primary malignant brain tumors in adults. Currently, surgical resection of the tumor mass, followed by adjuvant radiotherapy and chemotherapy are standard treatments for glioblastoma multiform but so far are not effective treatments. Thus, the development of a vaccine, as a safe and efficient strategy for prophylactic or therapeutic purposes against glioblastoma multiform is very necessary. The present study aimed to design the multi-domain vaccine for glioblastoma multiform. An in silico approach was used to select the most potent domains of proteins to induce the host's B- and T-cell immune response against glioblastoma multiform. IL-13Rα-2 (amino acid positions 27-144), TNC (amino acid positions 1900-2100), and PTPRZ-1(amino acid positions 731-884) were found to have potent inducible immune responses. So, we considered them for fusing with a linker A(EAAAK)
3 A to construct the multi-domain recombinant vaccine. The immuno-informatics analysis of the designed recombinant vaccine construct was performed to evaluate its efficacy. Although the designed recombinant vaccine construct did not show allergen property, its antigenicity was estimated at 0.78. The Physico-chemical properties of the recombinant vaccine construct were characterized and revealed the potency of the vaccine candidate. Then its secondary and tertiary structures, mRNA structure, molecular docking, and immune simulation were predicted using bioinformatics tools. Next, the designed recombinant vaccine construct was synthesized, and cloned into the pET28a vector and expressed in E. coli BL21. Besides, the circular dichroism spectroscopy was utilized for the investigation of the secondary structure changes of the recombinant vaccine construct. The results of the verification assessment of the recombinant vaccine construct expression indicated that in silico analysis was relatively accurate, and relatively change occurred on the protein secondary structure. In our future plan, the vaccine candidate that was confirmed by in silico tools should be validated by further in vitro and in vivo experimental studies., (Copyright © 2020. Published by Elsevier B.V.)- Published
- 2021
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32. Establishment and elicitation of transgenic root culture of Plantago lanceolata and evaluation of its anti-bacterial and cytotoxicity activity.
- Author
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Rahamooz-Haghighi S, Bagheri K, Sharafi A, and Danafar H
- Subjects
- Apigenin chemistry, Cell Line, Tumor, Chitosan metabolism, Diffusion, Drug Screening Assays, Antitumor, Gallic Acid chemistry, HEK293 Cells, Humans, Inhibitory Concentration 50, Iridoid Glucosides chemistry, Klebsiella pneumoniae drug effects, Methanol chemistry, Proteus vulgaris drug effects, Salmonella typhi drug effects, Anti-Bacterial Agents pharmacology, Culture Media, Microbial Sensitivity Tests, Plant Leaves genetics, Plant Roots genetics, Plantago genetics, Plants, Genetically Modified
- Abstract
Hairy root induction in Plantago lanceolata was optimized to take advantage of transformed root cultures. The highest frequency of transformation was achieved using leaf explant, A4 strain, pre-cultivation of explant, 150 µM Acetosyringone, 5 min inoculation, half-strength Murashige and Skoog basal medium as co-cultivation, and half-strength Gamborg's basal medium as a selective medium with 3% sucrose. Among the studied compound encompassing gallic acid, catalpol and apigenin, only the production of gallic acid in hairy roots was affected by 20 mg L
-1 AgNO3 and 100 mg L-1 chitosan at 24 hr which yielded 7.63, 4.76-fold increase in its content, respectively. The methanolic extracts of hairy roots elicited by 20 mg L-1 AgNO3 exhibited anti-bacterial activity (MIC and MBC = 25 mg mL-1 ) against Klebsiella pneumoniae , Proteus vulgaris and Salmonella typhi and anti-bacterial potential of non-elicited hairy roots of P. lanceolata (MIC = 25 mg mL-1 and MBC = 35 mg mL-1 ) were more active against Klebsiella pneumoniae and P. vulgaris than other bacteria. The methanolic extracts of the P. lanceolata hairy roots demonstrated significant cytotoxic activity on colorectal carcinoma cell line (SW-480) with IC50 = 250.65 ± 6.8 µg mL-1 in comparison to human embryonic kidney (HEK-293) with IC50 = 5263.65 ± 4.6 µg mL-1 . Plantago lanceolata hairy roots showed important biological activity explaining its role in traditional medicine.- Published
- 2021
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33. The effect of baicalein-loaded Y-shaped miktoarm copolymer on spatial memory and hippocampal expression of DHCR24, SELADIN and SIRT6 genes in rat model of Alzheimer.
- Author
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Aghajanzadeh M, Andalib S, Danafar H, Rostamizadeh K, and Sharafi A
- Subjects
- Alzheimer Disease genetics, Alzheimer Disease physiopathology, Animals, Disease Models, Animal, Drug Carriers chemistry, Flavanones administration & dosage, Hippocampus pathology, Male, Maze Learning drug effects, Nanoparticles, Nerve Tissue Proteins genetics, Oxidative Stress, Oxidoreductases Acting on CH-CH Group Donors genetics, Polyesters chemistry, Polyethylene Glycols chemistry, Polymers chemistry, Rats, Rats, Wistar, Sirtuins genetics, Alzheimer Disease drug therapy, Flavanones pharmacology, Hippocampus drug effects, Spatial Memory drug effects
- Abstract
In the present study, we successfully synthesized nanocarriers (NCs) based on Y-shaped miktoarm copolymers, Poly Ethylene Glycol-Lysine-(Poly Caprolactone)
2 (PEG-Lys-PCL2 ), which were loaded by baicalein (B) through the nanoprecipitation process to assess their in-vitro and in-vivo properties. We applied various methods and measurements including proton nuclear magnetic resonance (HNMR), dynamic light scattering (DLS), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), MTT assay, hemolysis test, lethal dose, real-time PCR, and Morris water maze. The results of DLS indicated that the size and zeta potential of the obtained NCs and B-loaded NCs were acceptable. Also, in-vivo and in-vitro biocompatibility examinations proved that miktoarm-based NCs were safe, and all rats treated with miktoarm-based NCs did not exhibit any remarkable weight loss during the experiment. The results of the Morris water maze (in-vivo test) revealed that the normal saline-treated group, as well as B-miktoarm + Scopolamine (M + B + S) and B-miktoarm-Tween80 + Scopolamine (M + B + T + S) pretreatment groups, spent more time in the target quadrant. Thus, this experiment showed that pretreatment of rats with M + B + S and M + B + T + S had the most effects on spatial memory. According to quantitative PCR analysis, we hypothesized that, in comparison with other experimental groups, pretreatment of rats with M + B + T + S could be more effective in preventing cholinergic dysfunction, brain oxidative stress and cognitive deficits which cause by Scopolamine HBr. This outcome may be partially due to the upregulation of DHCR24, SELADIN, and SIRT6 in entire of the hippocampal region of normal saline-treated and M + B + T + S pretreatment groups. These results may be because mimicking the cell membrane structure would be an excellent feature for miktoarm, and partial coating of Tween-80 can play a critical role for PEG-Lys-PCL2 -based NCs in crossing the brain cell membrane, and they can easily be uptaken by the cells. Eventually, all of the obtained data confirmed that PEG-Lys-PCL2 miktoarm star copolymers are suitable for delivering therapeutic agents to the brain for the treatment of Alzheimer's disease (AD). Also, it seems that baicalein should be taken into account as a potent compound for the treatment of AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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34. Improved synergic therapeutic effects of chemoradiation therapy with the aid of a co-drug-loaded nano-radiosensitizer under conventional-dose X-ray irradiation.
- Author
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Nosrati H, Charmi J, Abhari F, Attari E, Bochani S, Johari B, Rezaeejam H, Kheiri Manjili H, Davaran S, and Danafar H
- Subjects
- Animals, Cell Line, Tumor, Drug Carriers, Drug Delivery Systems, Mice, Particle Size, X-Rays, Antineoplastic Agents, Curcumin, Nanoparticles, Pharmaceutical Preparations, Radiation-Sensitizing Agents
- Abstract
The goal of this work is to harness the advantages of a targeted hybrid nanostructure, BSA-coated Fe
3 O4 (F)-Au heterodimer, as a radiosensitizer and co-delivery vehicle of chemotherapeutic drugs for enhanced synergic cancer therapy and protection of healthy tissues. F-Au-BSA-MTX-CUR combines the abilities of enhanced X-ray radiation therapy (F-Au), long blood circulation time (BSA), tumor targeting (MTX), enhanced chemotherapy (MTX and CUR), and protection of normal cells against the harmful effects of radiation (CUR). In this work, we present the radioprotective and radiosensitizing effects of CUR on normal tissues and the tumor site, respectively. After technical evaluation, drug loading, drug release behavior, hemolysis assay, transfection efficacy, and cellular uptake studies with fluorescence microscopy, the biosafety and toxicity of the nanostructure was assessed in vitro and in vivo. Also, to confirm its power to improve synergistic chemoradiation therapy in mice, the antitumor effects of the designed treatment plan were assessed in a 4T1-tumor bearing mouse model. The in vivo antitumor effect evaluation interestingly reveals outstanding therapeutic power of the final formulation (F-Au-BSA-MTX-CUR) and further requirement of CUR as a radioprotective. This result importantly revealed the radioprotection effect of CUR. Co-delivery of the chemotherapeutic drugs MTX and CUR, combined with the radiosensitizing effect of the F-Au heterodimer and the radioprotective effect of CUR, showed promising prospects in cancer therapy.- Published
- 2020
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35. Microemulsion and bovine serum albumin nanoparticles as a novel hybrid nanocarrier system for efficient multifunctional drug delivery.
- Author
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Gharbavi M, Danafar H, and Sharafi A
- Subjects
- Animals, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic pharmacology, Cattle, Drug Delivery Systems, Drug Liberation, Humans, MCF-7 Cells, Paclitaxel chemistry, Paclitaxel pharmacology, Antineoplastic Agents, Phytogenic administration & dosage, Drug Carriers chemistry, Nanoparticles chemistry, Paclitaxel administration & dosage, Serum Albumin, Bovine chemistry
- Abstract
The present study aims to: (a) design the versatile microemulsions (MEs) system for drug delivery; (b) use the bovine serum albumin nanoparticles for MEs system development; (c) characterize the physicochemical properties, cytotoxicity, and biocompatibility of the modified MEs (MMEs) system; (d) load of paclitaxel (PTX) and folate conjugate of MEs system; and (e) assess the potential of anticancer activity of MEs system. The physicochemical possessions, in vitro and in vivo cytotoxicity, and stability of MMEs system were characterized. The results of our study show that the MEs system was stable, having narrow particle size distribution, nontoxic, biocompatible, and not active for leukocyte proliferation. So it can be concluded that the MMEs system as a promising candidate for a targeted multifunctional drug delivery system (PTX and folate) that is called a smart MEs system., (© 2020 Wiley Periodicals, Inc.)
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- 2020
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36. Evaluation radioprotective effect of curcumin conjugated albumin nanoparticles.
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Nosrati H, Danafar H, Rezaeejam H, Gholipour N, and Rahimi-Nasrabadi M
- Subjects
- Animals, Cattle, Cell Line, Cell Survival drug effects, Cell Survival radiation effects, Curcumin chemistry, Curcumin pharmacology, Hemolysis drug effects, Humans, Mice, Inbred BALB C, Prodrugs administration & dosage, Prodrugs chemistry, Prodrugs pharmacology, Radiation-Protective Agents chemistry, Radiation-Protective Agents pharmacology, X-Rays adverse effects, Curcumin administration & dosage, Drug Carriers chemistry, Nanoparticles chemistry, Radiation-Protective Agents administration & dosage, Serum Albumin, Bovine chemistry
- Abstract
In this research, curcumin (CUR) conjugated albumin based nanoparticles (BSA-CUR) were designed for improvement and evaluation radioprotective effect of CUR. In this way, we have prepared BSA-CUR by covalently binding the CUR with BSA. Next, this synthesized prodrug was evaluated for physical and chemical properties by Fourier-transform infrared (FTIR), Dynamic light scattering (DLS), Transmission electron microscopy (TEM), Ultraviolet-visible (UV/Vis), and Differential scanning calorimetry (DSC) analysis. Furthermore, the chemical stability of designed prodrug was appraised. The result shows that the size of nanoparticles is 174.4 nm with a polydispersity index (PdI) of 0.191. The nanoparticles have a high loading capacity and show sustained release behavior. Loading of CUR to BSA not only could increase the chemical stability of CUR, but also could improve radioprotection efficacy of it's against X-Ray irradiation. The HHF-2 cells show 107% viability in the presence of BSA-CUR at a concentration of 50 µg/mL, whereas non-treated cells show 46% viability, under X-Ray irradiation. Also in vivo study results show that, four out of five mice have died when the mice irradiated by X-Ray and no received any treatment. Although, for a group that treated with BSA-CUR and also irradiated by X-Ray, median survival and survival rate was higher than CUR treated and control mice, and only two out of five mice have died. The result of this study proved that BSA-CUR can be used as a proficient vehicle for improving the potential radioprotective effect of CUR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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37. Anticancer effect of X-Ray triggered methotrexate conjugated albumin coated bismuth sulfide nanoparticles on SW480 colon cancer cell line.
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Faghfoori MH, Nosrati H, Rezaeejam H, Charmi J, Kaboli S, Johari B, and Danafar H
- Subjects
- Antimetabolites, Antineoplastic chemistry, Apoptosis drug effects, Apoptosis radiation effects, Bismuth chemistry, Cell Line, Tumor, Cell Survival drug effects, Cell Survival radiation effects, Colonic Neoplasms pathology, Drug Compounding, Humans, Methotrexate chemistry, Radiation-Sensitizing Agents chemistry, Serum Albumin, Bovine chemistry, Sulfides chemistry, Antimetabolites, Antineoplastic pharmacology, Bismuth pharmacology, Chemoradiotherapy, Colonic Neoplasms therapy, Drug Carriers, Methotrexate pharmacology, Nanoparticles, Radiation-Sensitizing Agents pharmacology, Serum Albumin, Bovine pharmacology, Sulfides pharmacology
- Abstract
The application of nanoparticles (NPs) as radio-sensitizers and carriers has opened up a new horizon to overcome the limitations of chemo and radiotherapy. In this study, bovine serum albumin-coated Bi
2 S3 NPs (Bi2 S3 @BSA NPs) were synthesized and evaluated in terms of their ability to be used as a radio-sensitizer and carrier for methotrexate (MTX). Physicochemical properties of MTX conjugated Bi2 S3 @BSA NPs (Bi2 S3 @BSA-MTX NPs) were characterized by DLS, TEM, FTIR, UV/Vis, and XRD analyses. After the evaluation of cellular uptake and intracellular localization, the cytotoxicity of the combination of Bi2 S3 @BSA-MTX NPs and X-Ray radiation was analyzed against the SW480 cell line. The synthesized NPs exhibited spherical-like shapes and homogenous morphology, possessing a hydrodynamic diameter of 140.2 ± 5.71 nm (mean ± SD) and zeta potential of -25 mV. Also, the release study showed that the release of MTX is faster and higher in the presence of the proteinase K enzyme than the absence of the enzyme. The results of in-vitro chemo-radiation therapy indicated that the viability of treated cells with Bi2 S3 @BSA-MTX NPs is significantly lower than the cells treated with Bi2 S3 @BSA NPs. Furthermore, cells treated with Bi2 S3 @BSA-MTX NPs showed a lower degree of viability when combined with X-Ray radiation in comparison with the absence of irradiation, which confirmed the ability of the Bi2 S3 @BSA-MTX NPs as radio-sensitizer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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38. In vivo and in vitro biocompatibility study of MnFe 2 O 4 and Cr 2 Fe 6 O 12 as photosensitizer for photodynamic therapy and drug delivery of anti-cancer drugs.
- Author
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Aghajanzadeh M, Naderi E, Zamani M, Sharafi A, Naseri M, and Danafar H
- Subjects
- Animals, Antineoplastic Agents metabolism, Biocompatible Materials administration & dosage, Biocompatible Materials metabolism, Cell Survival drug effects, Cell Survival physiology, Chromium metabolism, Dose-Response Relationship, Drug, Female, Ferric Compounds metabolism, HEK293 Cells, Humans, MCF-7 Cells, Male, Manganese Compounds metabolism, Mice, Photosensitizing Agents metabolism, Antineoplastic Agents administration & dosage, Chromium administration & dosage, Drug Delivery Systems methods, Ferric Compounds administration & dosage, Manganese Compounds administration & dosage, Photochemotherapy methods, Photosensitizing Agents administration & dosage
- Abstract
In The present project, a variety of MnFe
2 O4 (Mn) and Cr2 Fe6 O12 (Cr)-based nanocarriers (NCs) were synthesized as photosensitizer and NCs for delivery of chemotherapeutic curcumin (CUR) and provide a new structure for Photodynamic Therapy (PDT). For determining efficiency of NCs release study, MTT assay, lethal dose test and hemolysis assay were carried out. The release study showed the release of CUR from NCs was pH-dependent, but, every NCs had its own behavior for releasing the drug. The data acquired from the release study showed the CUR release from Mn can reach to over 90% at acidic media instead of 41% at neutral media. However, the CUR released from Cr were approximately equal as Cr had equal zeta potential at both media. Hemolysis activity and lethal dose test displayed the cytotoxicity of NCs was neglectable at both in vitro and in vivo study. Also, the results of anti-cancer activity assay (MTT assay) showed that both of Cr and Mn NCs are suitable systems for PDT. Therefore, the results demonstrated that Mn is suitable NCs for PDT and anticancer drugs delivery of therapeutic drugs.- Published
- 2020
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39. Enhanced flavonoid production in hairy root cultures of Scutellaria bornmuelleri by elicitor induced over-expression of MYB7 and FNSП2 genes.
- Author
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Gharari Z, Bagheri K, Danafar H, and Sharafi A
- Subjects
- Flavonoids genetics, Gene Expression Regulation, Plant, Plant Roots growth & development, Plant Roots microbiology, Agrobacterium physiology, Host-Pathogen Interactions genetics, Scutellaria genetics, Scutellaria microbiology, Transcription Factors genetics, Transcription Factors metabolism
- Abstract
For the purpose of the current study, hairy root induction in S. bornmuelleri, which is an important medicinal plant, was examined using a particular protocol. Accordingly, some factors such as four strain types of Agrobacterium rhizogenes (A4, A13, MSU440 and ATCC15834), three different explants, namely stem, petiole and leaf, two co-cultivation media, i.e. full and half-MS were studied. Besides, two inoculation methods including injection and immersion as well as three inoculation times (5, 7 and 10 min) were closely taken into account. Utilizing injection method by MSU440 strain, hairy root induction took place in stem explants, and a remarkable increase in transformation frequency (100%) was observed in half-strength MS medium. Methyl jasmonate (MeJA, 100 μM), methyl-b-cyclodextrin (b-CD, 0.7, 7 and 14 mM) and Chitosan (Chi, 50, 100 and 200 mg/l) were used either individually or in a combined way to elicitation. Based on the HPLC results, production of chrysin, wogonin and baicalein increased 9.15, 10.56 and 13.25 times after elicitation of hairy roots by MeJA + Chi. In addition, transcripts of FNSП2 and MYB7, two important genes involved in the flavonoid biosynthesis pathway, were studies. By applying Chi and MeJA + Chi elicitor, the expression of both genes increased noticeably. It can be concluded that the mentioned hairy root culture system of S. bornmuelleri can be an alternative to flavonoids production. Moreover, there is a direct and positive relationship between the expression of FNSП2 and MYB7 genes as well as the level of three flavonoids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
- Published
- 2020
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40. Biotin-functionalized copolymeric PEG-PCL micelles for in vivo tumour-targeted delivery of artemisinin.
- Author
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Nosrati H, Barzegari P, Danafar H, and Kheiri Manjili H
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Drug Carriers toxicity, Drug Liberation, Hemolysis drug effects, Humans, Hydrogen-Ion Concentration, MCF-7 Cells, Methylation, Mice, Nanoparticles chemistry, Xenograft Model Antitumor Assays, Artemisinins chemistry, Artemisinins pharmacology, Biotin chemistry, Drug Carriers chemistry, Lactones chemistry, Micelles, Polyethylene Glycols chemistry
- Abstract
Artemisinin is used as an antimalarial and anticancer agent with minimal toxic effects on the host body. Biotin-PEG-PCL polymers have been used for targeted drug delivery to cancer, as well as to improve the pharmacokinetics of the drug and reduce its effects. In this study, biotin-conjugated copolymers were fabricated with polymerization of the ring opening method and the properties of copolymer and nanoparticles were investigated using various techniques. The toxicity of artemisinin and its nanoparticles have been investigated on MCF-7 and normal HFF2 cells. The results showed that the encapsulation efficacy of artemisinin in nanoparticles was 45.5 ± 0.41%. The release profile of the drug indicates that the release is slow and controlled and is approximately pH dependent. The results of artemisinin cell culture on human breast cancer cells showed that biotin-PEG-PCL nanoparticles had an inhibitory effect on MCF-7 cells and had no toxic effects on HFF2 cells. Anticancer activity in vivo in the 4T1 breast cancer model showed that tumour volumes were decreased up 40 mm
3 by ART-loaded micelles and 76 mm3 by free ART, compared to the control group (2150 mm). In vivo results showed that this formulation significantly increases the accumulation of substances in the tumours. Therefore, the molecular formulation of ART-based copolymers can be a desirable process for cancer treatment purposes.- Published
- 2019
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41. Facile green synthesis of bismuth sulfide radiosensitizer via biomineralization of albumin natural molecule for chemoradiation therapy aim.
- Author
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Nosrati H, Abhari F, Charmi J, Rahmati M, Johari B, Azizi S, Rezaeejam H, and Danafar H
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Bismuth chemistry, Cattle, Chemistry Techniques, Synthetic, Coated Materials, Biocompatible chemical synthesis, Coated Materials, Biocompatible chemistry, Coated Materials, Biocompatible pharmacology, Curcumin chemistry, Curcumin pharmacology, Drug Carriers chemical synthesis, Drug Carriers chemistry, Drug Carriers pharmacology, Drug Liberation, Green Chemistry Technology, HT29 Cells, Humans, Nanoparticles chemistry, Particle Size, Radiation-Sensitizing Agents chemical synthesis, Radiation-Sensitizing Agents chemistry, Radiation-Sensitizing Agents pharmacology, Sulfides chemistry, Bismuth pharmacology, Chemoradiotherapy, Minerals chemistry, Serum Albumin, Bovine chemistry, Sulfides chemical synthesis, Sulfides pharmacology
- Abstract
High atomic number Z, nanoparticles are able to enhance the photoelectric and Compton effects under X-Ray irradiation resulting the increase of radiation therapy efficacy. To achieve enhanced radiation therapy, Bi
2 S3 biocompatible particles coated with bovine serum albumin (BSA) (Bi2 S3 @BSA HNPs) were prepared through a BSA-mediated biomineralization procedure under green conditions. Then, to achieve improved chemo-radiation therapy against HT-29 cancer cells, curcumin (CUR) as natural anti-cancer therapy agent loaded on the Bi2 S3 @BSA (Bi2 S3 @BSA@CUR HNPs). Next, this synthesized nanodrug was evaluated for physical and chemical properties and in vitro cytotoxicity studies. Here, in vitro enhanced chemo-radiation combination therapy power was evaluated against HT-29 cell line under 2 Gy and 6 Gy X-ray irradiation doses. The Bi2 S3 @BSA HNPs without irradiation rarely affect cell viability which shown the non-toxicity of Bi2 S3 @BSA HNPs. The result of this study proved that Bi2 S3 @BSA@CUR HNPs can be used as both proficient vehicles for effective delivery of CUR and radiosensitizer in the treatment of cancer. In addition, the result of this study confirmed that the combination of high Z-element nanoradiosensitizer, Bi2 S3 @BSA HNPs, with a natural anti-cancer drug, CUR, enhanced therapeutic power against HT-29 cells.- Published
- 2019
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42. Methotrexate anticancer drug delivery to breast cancer cell lines by iron oxide magnetic based nanocarrier.
- Author
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Attari E, Nosrati H, Danafar H, and Kheiri Manjili H
- Subjects
- Female, Humans, MCF-7 Cells, Antimetabolites, Antineoplastic chemistry, Antimetabolites, Antineoplastic pharmacokinetics, Antimetabolites, Antineoplastic pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Breast Neoplasms pathology, Drug Carriers chemistry, Drug Carriers pharmacokinetics, Drug Carriers pharmacology, Magnetite Nanoparticles chemistry, Magnetite Nanoparticles therapeutic use, Methotrexate chemistry, Methotrexate pharmacokinetics, Methotrexate pharmacology
- Abstract
In this study, we have achieved to provide an efficient method for production of iron oxide magnetic nanoparticles (MNPs) with arginine capping using in situ and one-pot co-precipitation method. As a novel drug delivery system, methotrexate (MTX) was conjugated to the obtained nanoparticles. These MNPs conjugate can potentially use in controlled drug delivery as carrier, and in magnetic resonance imaging as a contrast agent. Also, these nanoparticles can serve as a target in cancer therapy and diagnosis. These MNPs were covalently bond with MTX and can target the majority of cancer cells that their surfaces overexpressed by folate receptors. These conjugated nanoparticles were obtained through amide bond between the amine groups on their surface and the carboxylic acid end groups on MTX due to being functionalized with arginine. MTX was cleaved from nanoparticles according to drug release experiments in the presence of protease-like lysosomal conditions. Fe-Arg-MTX was characterized by transmission electron microscopes, dynamic light scattering, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. Furthermore, vibrating sample magnetometry analysis showed excellent magnetic properties of them. The average particle size of Fe-Arg-MTX was approximately 27 nm. The result revealed that the bare nanoparticles have no cytotoxicity against MCF-7, 4T1, and HFF-2 cell lines. Hemolysis assay showed that these nanoparticles are biocompatible. Regarding the research success, an efficient technique can be presented for drug delivery and controlled release and for studying cancer-fighting in alive creature's bodies., (© 2019 Wiley Periodicals, Inc.)
- Published
- 2019
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43. Tumor Targeted Albumin Coated Bismuth Sulfide Nanoparticles (Bi 2 S 3 ) as Radiosensitizers and Carriers of Curcumin for Enhanced Chemoradiation Therapy.
- Author
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Nosrati H, Charmi J, Salehiabar M, Abhari F, and Danafar H
- Abstract
Combination therapy such as radiotherapy combined with chemotherapy has attracted excessive interest in the new cancer research area. Therefore, developing nanobiomaterials for combination of radiotherapy and chemotherapy is required for more powerful and successful cures. Because of the amazing X-ray sensitization proficiency of Bi based nanoparticles, in this work, we synthesized and used Bi
2 S3 as an enhancer of X-ray radiation therapy, and furthermore, Bi2 S3 served as carrier of curcumin (CUR), a chemotherapy drug, for the goal of combination therapy. Additionally, we selected and conjugated folic acid (FA) as a targeting molecule for the direction of the designed system to the tumor site. After characterization of drug loaded FA conjugated Bi2 S3 @BSA nanoparticles (Bi2 S3 @BSA-FA-CUR) and in vitro and in vivo safety assessment, we applied it for enhanced chemotherapy and X-ray radiation therapy in cancer cells and a tumor bearing mice model. Moreover, the CT contrast ability of synthesized nanoparticles was examined. Here, we (1) for the first time developed the novel and targeted CUR loaded Bi2 S3 @BSA (Bi2 S3 @BSA-FA-CUR) to promote chemoradiation therapy in 4T1 cells and breast tumor in mice; (2) found the synthesized nanoparticles to have good stability; (3) injected a single dose of the designed radiosensitizer for cancer therapy; and (4) used a conventional X-ray dose, 2Gy, for X-ray radiation therapy. The result of in vivo X-ray radiotherapy shows that the mice tumors vanished near 3 weeks after radiation. Interestingly, these results show that Bi2 S3 @BSA-FA-CUR with the aid of X-ray can clearly promote the efficacy of chemoradiation therapy.- Published
- 2019
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44. Preparation and Evaluation of pH Sensitive Novel Anticancer Drug Carrier Based on Magnetic Chitosan Quartets.
- Author
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Danafar H, Asadi F, Sharafi A, and Manjili HK
- Subjects
- Cell Line, Tumor, Cell Survival drug effects, Contrast Media chemistry, Drug Carriers chemistry, Drug Delivery Systems methods, Drug Liberation, Humans, Hydrogen-Ion Concentration, MCF-7 Cells, Spectroscopy, Fourier Transform Infrared methods, X-Ray Diffraction methods, Antineoplastic Agents chemistry, Chitosan chemistry, Magnetite Nanoparticles chemistry
- Abstract
Chitosan-coated magnetic nanoparticles are an appropriate drug delivery method which can improve the therapeutic properties of chemotherapy agents and also can be useful as MRI contrast agent for early cancer diagnosis. This research discovers the optimization of the possible therapeutic effects of Chitosan- citric acid- Fe
3 O4 - CUR quartets. Chitosan as a natural polymer can use to encapsulate citric acid modified Fe3 O4 nanoparticles. The successful preparation of CUR-loaded nano-carriers was confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM) techniques. Moreover, the hemolysis test was used for the study of hemobiocompatibility. The loading capacity and encapsulation efficiency of CUR molecules were 11±0.09% and 49.5±0.41%, respectively. The anticancer effect of the void of CUR and CUR-loaded nano-carriers were compared by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the treated MCF-7 cell lines. It can be concluded that the use of these nanoparticles are a better and more efficient approach for the controlled and slow release of CUR in the cancer treatment., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)- Published
- 2019
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45. Corrigendum to "Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles" [Eur. J. Pharm. Biopharm. 116 (2017) 17-30].
- Author
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Manjili HK, Ghasemi P, Malvandi H, Mousavi MS, Attari E, and Danafar H
- Published
- 2019
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46. Anti-inflammatory effect of rosuvastatin using diblock amphiphilic copolymer: Synthesis, characterization, in vitro and in vivo study.
- Author
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Aghajanzadeh M, Ghannad F, Zamani M, Andalib S, and Danafar H
- Subjects
- Animals, Anti-Inflammatory Agents pharmacology, Drug Liberation, HEK293 Cells, Hemolysis drug effects, Humans, Indomethacin pharmacology, Indomethacin standards, Lipids chemistry, Male, Micelles, Models, Animal, Polyesters chemistry, Polyethylene Glycols chemistry, Rats, Wistar, Rosuvastatin Calcium pharmacology, Anti-Inflammatory Agents chemistry, Nanocapsules chemistry, Polyesters chemical synthesis, Polyethylene Glycols chemical synthesis, Rosuvastatin Calcium chemistry
- Published
- 2019
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47. In vivo study of mPEG-PCL as a nanocarriers for anti-inflammatory drug delivery of simvastatin.
- Author
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Zamani M, Shirinzadeh A, Aghajanzadeh M, Andalib S, and Danafar H
- Subjects
- Animals, Anti-Inflammatory Agents pharmacokinetics, Anti-Inflammatory Agents therapeutic use, Anticholesteremic Agents pharmacokinetics, Anticholesteremic Agents therapeutic use, Drug Delivery Systems, Edema drug therapy, Male, Micelles, Rats, Wistar, Simvastatin pharmacokinetics, Simvastatin therapeutic use, Anti-Inflammatory Agents administration & dosage, Anticholesteremic Agents administration & dosage, Drug Carriers chemistry, Polyesters chemistry, Polyethylene Glycols chemistry, Simvastatin administration & dosage
- Abstract
Purpose: In this study, methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL) di-block copolymers were synthesized. The purpose of this work is to investigate the in vivo anti-inflammatory effects of simvastatin-loaded micelles., Methods: The structure of synthesized copolymers was characterized by using HNMR, FTIR, and GPC techniques. Simvastatin was encapsulated in micelles through a single-step nano-precipitation method, leading to the formation of simvastatin-loaded mPEG-PCL (simvastatin-mPEG-PCL) micelles. In this study, the anti-inflammatory effects of simvastatin/mPEG-PCL micelles versus indomethacin were investigated in acute inflammation-induced rats. The paw edema thickness was measured 1, 2, 3, and 4 h after injection of formulation. The inhibition of edema in various groups were calculated and reported by percentages., Results: The results showed that the zeta potential of micelles was about -14.9 ± 0.47 mV and the average size was in range of 66.10 ± 0.34 nm. Simvastatin was encapsulated in mPEG-PCL micelles with a loading capacity of 9.63 ± 0.87% and an encapsulation efficiency of 64.20 ± 0.79%. Simvastatin and simvastatin-mPEG-PCL micelles showed significant anti-inflammatory activity in the present study., Conclusions: This study revealed that simvastatin and simvastatin/mPEG-PCL micelles both have anti-inflammatory effects and suggested that statins have potential anti-inflammatory activity along with their lipid lowering properties.
- Published
- 2019
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48. Multifunctional nanoparticles from albumin for stimuli-responsive efficient dual drug delivery.
- Author
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Nosrati H, Abhari F, Charmi J, Davaran S, and Danafar H
- Subjects
- Animals, Antimetabolites, Antineoplastic chemistry, Breast Neoplasms pathology, Cattle, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Liberation, Drug Screening Assays, Antitumor, Female, Methotrexate chemistry, Mice, Mice, Inbred BALB C, Molecular Structure, Structure-Activity Relationship, Tumor Cells, Cultured, Antimetabolites, Antineoplastic pharmacology, Breast Neoplasms drug therapy, Drug Delivery Systems, Methotrexate pharmacology, Nanoparticles chemistry, Serum Albumin, Bovine chemistry
- Abstract
In this project methotrexate (MTX) conjugated albumin based nanoparticles (MTX-BSA) loaded with curcumin (CUR) drug (CUR-MTX-BSA) for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy were designed. Co-delivery is a new strategy which minimize the amount of each drug, reduce of side effects and also to achieve the synergistic effect for cancer therapies. The MTX was conjugated to albumin via covalent bond. Next, this synthesized prodrug loaded with CUR. Afterward, the formulations were evaluated for physical and chemical properties by DLS, TEM, FTIR, UV/Vis, DSC analysis, in vitro cytotoxicity and in vivo biocompatibility studies. Furthermore, the drug loading and release study were evaluated. Proteinase K enzyme was used to break amid bond between MTX and BSA and also amidic bonds in BSA structure. Administration of up to 2000 mg/kg of BSA to healthy animals was non-toxic and all treated mice were still alive after 24 h. The result of this study proved that CUR-MTX-BSA can be used as a proficient vehicle for effective co-delivery of CUR and MTX in the treatment of cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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49. In vivo and in vitro biocompatibility study of novel microemulsion hybridized with bovine serum albumin as nanocarrier for drug delivery.
- Author
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Gharbavi M, Manjili HK, Amani J, Sharafi A, and Danafar H
- Abstract
The present study aimed to synthesize triacetin-microemulsion (T-ME) and T-ME hybridized with bovine serum albumin nanoparticles (T-BSA-ME) having narrow particle size distribution and versatile carrier systems as a novel microemulsion system. The suggested ME system was characterized by Fourier Transform Infrared spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Atomic Force Microscopy (AFM). The physicochemical properties of microemulsion system including particle size, PDI and ζ-potential, refractive index, Conductivity, %Transmittance, pH, and rheological behavior were also evaluated. In vivo biocompatibility was done using Median Lethal Dose (LD 50) calculated and trialed to evaluate the acute toxicity. In Addition, hemolysis and leukocyte proliferation assay were characterized to evaluate in-vitro biocompatibility of the suggested MEs systems. Moreover, cytotoxicity of MEs systems was also investigated on HFF-2 and HEK-293 cells. The presence of BSA NPs as a macromolecular biomaterial hybridized with T-ME reduced the cytotoxicity. The properties of the suggested MEs system proposed the T-ME hybridized with BSA-NPs as a promising candidate for co-delivery and multifunctional biomedicine applications.
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- 2019
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50. New Insight about Biocompatibility and Biodegradability of Iron Oxide Magnetic Nanoparticles: Stereological and In Vivo MRI Monitor.
- Author
-
Nosrati H, Salehiabar M, Fridoni M, Abdollahifar MA, Kheiri Manjili H, Davaran S, and Danafar H
- Subjects
- Animals, Arginine chemistry, Biocompatible Materials metabolism, Biocompatible Materials pharmacology, Cell Line, Cell Proliferation drug effects, Contrast Media chemistry, Contrast Media metabolism, Hemolysis drug effects, Humans, Kidney diagnostic imaging, Liver chemistry, Liver metabolism, Magnetic Resonance Imaging, Magnetite Nanoparticles toxicity, Mice, Mice, Inbred BALB C, Polyethylene Glycols chemistry, Tissue Distribution, Biocompatible Materials chemistry, Ferric Compounds chemistry, Magnetite Nanoparticles chemistry
- Abstract
Iron oxide magnetic nanoparticles (IONPs) have attracted enormous attention because of their extensive medicinal and industrial applicability. PEGylated L-arginine modified iron oxide magnetic nanoparticles (PEG-Arg@IONPs) were synthesized and functioned in the present research as MRI contrast agents considered in vivo BALB/c model. The Synthesized PEG-Arg@IONPs were tracked in certain time intervals by MRI. The intensity of MR imaging of kidneys increased after administration of PEG-Arg@IONPs, which could confirm the emission of these nanoparticles by kidneys shortly after administration. Although PEG-Arg@IONPs were uptake by liver within 2 hours after injection, whereas, the signal change intensity of spleen, heart and kidneys confirmed that PEG-Arg@IONPs existed in other organs. The results illustrated that IONPs coated with PEGylated natural amino acid thin layers had a long circulation time and could be served as T
2 contrast agents for diagnosis purpose. Notably, to the best of our knowledge, it was the first time the biocompatibility and biodegradability of IONPs was studied and evaluated by stereological and MRI technique.- Published
- 2019
- Full Text
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