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Among the potent anticancer agents, methotrexate (MTX) is very effective against many different types of cancer cells. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. In the present study self‐assembled MTX conjugated mPEG‐PCL copolymer encapsulating gold nanoparticles (AuNPs) hybrid (mPEG‐PCL‐MTX@Au) was developed as both drug carrier and radiosensitizer. After successful synthesis and characterization of hybrids with different techniques such as hydrogen nuclear magnetic resonance (HNMR), Fourier transform infrared spectroscopy (FTIR), ultraviolet–visible (UV‐Vis), x‐ray diffraction analysis (XRD), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The anticancer activity of designed system was evaluated with a series of biological assays. TEM image indicate that AuNPs encapsulated by self‐assembled mPEG‐PCL‐MTX NPs. It was found that the micelle of that shown in the TEM image contains nine gold nanoparticles (NPs). The hydrodynamic diameter of mPEG‐PCL‐MTX@Au was 81.40 ± 8 nm. As a result, at acidic pH, which simulates tumor tissue, the most drug release is done compared to neutral pH conditions, which are the physiological conditions of the body. About 70% of the drug was released in acidic pH, while in alkaline pH, it was about 35%. The effectiveness of cancer treatment was significantly improved by using developed NPs, which introduces simultaneous chemotherapy and radiotherapy. MTT and apoptosis assays show that the mPEG‐PCL‐MTX@Au as the final formulation improves the radiosensitivity of the 4T1 breast cancer cells and also remarkably kills breast cancer. Furthermore, the result revealed that designed hybrid system extremely able to produce reactive oxygen species (ROS) within cancer cells. These results offer powerful evidence for the potential capability of mPEG‐PCL‐MTX@Au in radiosensitization of malignant tumors and opens up a new avenue of research in this area. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The improvement of high‐Z‐based metallic nanostructures as radiosensitizers with high monolithicity and versatility by superadditive therapeutic track and the good protective effect is considerable, but they are limited by some problems such as nonideal selectivity for the target tissue. In this study, nanosystems were developed to enhance the efficacy of radiotherapy and reduce cancer cell survival based on innovative gold (Au) functionalized oxygen‐single‐walled carbon nanotubes (O‐SWCNTs). We illustrate the use of folic acid (FA) as a targeting agent and bovine serum albumin (BSA) to stabilize the physiological environment and increase durability. The physical and chemical properties of the nanosystems were evaluated using 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) techniques. Finally, the MTT assay was used to investigate the therapeutic effects of nanoparticles in the 4 T1 mouse breast cancer model in the presence and absence of X‐rays. So, the cancer cells experienced a more effective reduction in survival after receiving O‐SWCNTs‐Au‐BSA‐FA + 8 Gy than O‐SWCNTs‐BSA, Au‐BSA‐FA, and O‐SWCNTs‐Au‐BSA + 8 Gy groups. [ABSTRACT FROM AUTHOR]

Due to the increased incidence and population growth that has been leading to growing number of cases worldwide, early diagnosis and treatment of cancer is crucial. Low density cancer tissue cannot be diagnosed before progressing toward a metastatic stage. Thus, theranostic systems play a significant role in assisting timely diagnosis and treatment. The combination of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents in a single probe is of high importance and necessity, where individual strengths of each approach can be merged while shortcomings of each modality could be compensated. With this motivation, we have developed and synthesized Bi2S3@BSA‐Fe3O4 nanoparticles as a dual MRI/CT contrast agent and carrier of curcumin (CUR) as natural anticancer drug. The nanoparticles shortened both the longitudinal (T1) and transverse (T2), MRI relaxation times, with a more distinct effect on producing negative contrast (T2) images with a relaxivity (r2) of 54.73 mM−1 s−1. The magnetite/bismuth hybrid nanoparticle also was capable of increasing CT image contrast. Further, in vitro cytotoxicity assay showed high biocompatibility of the synthesized nanoparticles. Furthermore, in vitro cytotoxicity assay on cancer cells showed high anticancer activity of the synthesized nanoparticles. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticles (MNPs) functionalized with methotrexate (MTX)‐conjugated bovine serum albumin (BSA) as a biocompatible drug delivery vehicle were synthesized using a facile method. Characterization of the functionalized MNPs (Fe3O4@BSA‐MTX NPs) was performed using various techniques including UV–visible spectroscopy, dynamic light scattering, vibrating sample magnetometry and X‐ray diffraction. The particle size and zeta potential of Fe3O4@BSA‐MTX NPs were 105.7 ± 3.81 nm (mean ± SD) and −18.2 mV, respectively. MTX release from Fe3O4@BSA‐MTX NPs showed an enzyme‐dependent release pattern. Hemo‐biocompatibility of Fe3O4@BSA‐MTX NPs was confirmed using hemolysis test. In addition, the cytotoxicity of functionalized MNPs and free MTX against MCF‐7 cell line was investigated using MTT assay. The results of experiments revealed that the Fe3O4@BSA‐MTX NPs as a biocompatible carrier could improve the therapeutic effect of MTX. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this project, a core‐shell polymersome based on miktoarm star‐copolymer:methoxy poly‐ethylene glycol‐lysine‐(poly‐caprolactone)2 was synthesized by a new method as controlled targeted drug delivery systems for codelivery of the chemotherapeutic methotrexate (MTX) and curcumin (CUR). Some properties of these nanocarriers (NCs), such as surface morphology, structure, surface charge, stability, and biocompatibility, were evaluated by proton nuclear magnetic resonance, dynamic scanning colorimetry, Fourier‐transform infrared spectroscopy, dynamic light scattering, atomic force microscopy, critical aggregation concentration, hemolysis test, MTT assay, and lethal dose 50 (LD50). The AFM results showed that the uniform spherical morphology of NCs have an average size of about ∼60 nm. The drug loading of NCs was about 14.13 and 10.93% for CUR and MTX, respectively. The NCs revealed pH‐sensitivity in drug release. The release of drugs from miktoarm‐based NCs in neutral pH was lower than in acidic medium because of faster degradation of polymersome in acidic environment. MTT assay results showed that the drug‐loaded NCs did not show significant toxicity due to which cell viability maintain over 82% at 300 μg/mL concentration. Also, synthesized miktoarm showed hemolysis lower than 3%. This result was repeated in LD50, and all mice which treat with 5000 mg/kg were still alive after 24 h. These result confirmed safety of miktoarm star copolymer. Eventually, the goal of this study is the application of water‐soluble star copolymers miktoarm with pH dependent release properties for designing a new drug delivery carrier and using CUR for enhancing anticancer properties of MTX. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2817–2826, 2018. [ABSTRACT FROM AUTHOR]

Abstract: In this study, magnetic nanoparticles (MNPs) coated with glycine (F‐Gly NPs) and conjugated with methotrexate (MTX) (F‐Gly‐MTX NPs) were synthesized through a coprecipitation method followed by amidation reaction between the carboxylic acid end groups on MTX and the amine groups on the MNPs surface and studied its cytotoxic effect in vitro. The successful conjugating of MTX onto the nanoparticles (NPs) was confirmed by X‐ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, vibrating sample magnetometer, and transmission electron microscopy techniques. The results showed that the average size was 46.82 ± 5.03 nm. This target drug delivery system is dependent on the release of the MTX within the lysosomal compartment. Hemolysis assay and cytotoxicity study results on HFF‐2 and HEK‐293 cell lines show that as prepared MNPs are biocompatible. The cytotoxicity of void of the MTX and F‐Gly‐MTX NPs were compared to each other by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay of the treated MCF‐7 cell line. Enzymatic release studies exhibited the release of the MTX via peptide bond cleavage in the presence of proteinase K. These studies specify that the F‐Gly‐MTX NPs have a very remarkable anticancer effect, for breast cancer cell line. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1646–1654, 2018. [ABSTRACT FROM AUTHOR]

Metal organic frameworks (MOFs) UiO‐66 (UiO stands for University of Oslo) and NH2‐UiO‐66 were prepared and characterized as sorbent (antidotal agents) for curcumin (CUR) adsorption. The structure of products were characterized by X‐ray powder diffraction (XRD), Field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), Attenuated Total Reflectance‐Fourier transform infrared spectroscopy (ATR‐FTIR), and N2 adsorption–desorption measurements. FESEM showed NH2‐UiO‐66 displayed symmetrical crystals with triangular base pyramid morphology, with the particle size around 100 nm and uniform size distribution. Adsorption capacities of CUR/MOFs with different mass ratios in the feed were investigated in the present study, and this investigation revealed that when the CUR/MOFs with mass ratio was around 0.4, the absorption capacity of NH2‐UiO‐66 had tended to maximum. Although, functionalization reduced the specific surface area and free volume, introducing polar amine groups could improve the affinity of NH2‐UiO‐66 respect to CUR. Kinetic studies showed that the kinetic data are well fitted with the pseudo‐ second‐order model. MTT assay revealed that MOFs at the concentration range of 0–560 μg/ml had no cytotoxic effect on the Human Foreskin Fibroblast normal cell line (HFF‐2). These results suggest that these MOFs could be safe as sorbent for adsorb CUR from the body. [ABSTRACT FROM AUTHOR]

We report the synthesis of iron oxide magnetic nanoparticles (IONPs) coated with various natural amino acids (AAs) using a one‐pot reaction in an aqueous medium. Several AAs, which contained hydrophilic and hydrophobic groups, were selected to study their effects on size, morphology and toxicity of IONPs. Functionalized IONPs were characterized using X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and scanning and transmission electron microscopies. Furthermore, vibrating sample magnetometry analysis shows these nanoparticles have excellent magnetic properties. Cellular toxicity of IONPs was also investigated on HFF2 cell lines. The AA‐coated IONPs are non‐toxic and biocompatible. Natural AA‐coated IONPs show a potential for their development in in vitro and in vivo biomedical fields due to their non‐toxicity, good ζ‐potential and related small size and narrow size distribution. [ABSTRACT FROM AUTHOR]

In this study, Bi2S3@BSA–Bio–MTX nanoparticles (NPs) were synthesized for the first time by bovine serum albumin (BSA)‐mediated biomineralization (Bi2S3@BSA NPs) followed by covalent bonding of biotin (Bio) and methotrexate (MTX) on the surface of the Bi2S3@BSA NPs via carbodiimide chemistry. The synthesized NPs were globular and exhibited uniform morphology with a hydrodynamic diameter of 107.6 ± 6.81 nm (mean ± standard deviation) and zeta potential of −20.9 ± 2.18 mV. Drug release from Bi2S3@BSA–Bio–MTX NPs indicated an enzyme‐dependent release pattern. The in vitro biocompatibility of NPs was confirmed by investigating their cytotoxicity against the HEK‐293 cell line and hemolysis assay test, whereas the in vivo biocompatibility of the NPs was evaluated and confirmed by the lethal dose 50 (LD50) test. To evaluate the in vitro anticancer activity of the functionalized NPs and MTX, their cytotoxic effects was assessed against 4T1 cancer cells by 5‐dimethylthiazol‐z‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay with and without X‐ray radiation. Results showed that Bi2S3@BSA–Bio–MTX NPs have excellent anticancer activity, especially following X‐ray radiation. [ABSTRACT FROM AUTHOR]

In this time researchers make a great efforts to develop new hybrid nanoparticles for medical and pharmaceutical applications. Fe3O4‐Au hybrid heterodimers have been prepared with superior properties for various claims. Unfortunately, Fe3O4‐Au heterodimers are not stable in the physiological medium. In this study, we employed the albumin macromolecules as a stabilizer of Fe3O4‐Au hybrid nanoparticles (noted as Fe3O4‐Au‐BSA hybrid nanoparticles). After characterization of synthesized nanoparticles by FTIR, UV–Vis, TEM, DLS, DSC, VSM and XRD techniques, the in vitro and in vivo biocompatibility of these nanoparticles were also evaluated. We encountered with an amazing result which confirmed nanoparticles could be stabilized by linking the BSA on the surface of Fe3O4‐Au heterodimers. Also, intravenous injection of Fe3O4‐Au‐BSA hybrid nanoparticles up to 400 mg/kg to Balb C mice show that these nanoparticles were non‐toxic. The biocompatibility and stereological study had been performed for more than 30 days after nanoparticles administration, using hystomorphometric analysis. Remarkably, to the best of our knowledge, it was the first time the biocompatibility and biodegradability of Fe3O4‐Au were studied and evaluated by stereological technique. Further promotion and biomedical usage of this type of hybrid nanoparticles are underway in our laboratory. [ABSTRACT FROM AUTHOR]

In this study we described the production of curcumin (CUR) loaded L‐tyrosine (Tyr coated Fe3O4 magnetic nanoparticles. CUR loaded Tyr modified Fe3O4 nanoparticles (F@Tyr@CUR NPs) were analyzed by transmission electron microscopy, fourier transform infrared spectroscopy, thermo gravimetric analysis, vibrating sample magnetometer, X‐ray diffraction and dynamic light scattering techniques. The dynamic light scattering results showed that the ζ‐potential of F@Tyr@CUR NPs was about −15.4 mV. Also, the internal average size was about 25.81 ± 3.31 (mean ± SD (n = 30)) nm. The drug loading and encapsulation efficiency were 8.87 ± 0.09% and 35.21 ± 0.41%, respectively. In addition, hemolysis test on human red blood cells were conducted to determine the hemocompatibility of F@Tyr@CUR NPs. Next, MTT assays on HEK‐293 were conducted to determine the toxicity of F@Tyr@CUR NPs. Lastly, the potential anticancer effect of F@Tyr@CUR NPs was considered on MCF‐7 cancer cell line. The outcomes indicated that these F@Tyr@CUR NPs are appropriate for delivery of CUR anticancer drug. Also, the MRI training established the effectiveness of Fe3O4 magnetic nanoparticles as contrast agent for the revealing of tumor as evidenced from the phantom images as well as higher T2 relaxivity. We have identified and developed a biocompatible drug delivery system (F@Tyr NPs), which could be used to delivery of chemotherapeutic agents such as CUR. Also, the MRI study demonstrated the effectiveness of Fe3O4 nanoparticles as contrast agent for the early detection of tumor as evidenced from the phantom images as well as higher T2 relaxivity. [ABSTRACT FROM AUTHOR]