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Triple-negative breast cancer (TNBC) presents significant treatment challenges due to its aggressive nature. Human serum albumin (HSA) is a promising drug delivery platform, offering high binding capacity, biocompatibility, and reduced toxicity. Lapatinib (LAP), a tyrosine kinase inhibitor for TNBC, is hindered by poor water solubility and toxicity. To address these issues, LAP was encapsulated within HSA (HSA-LAP), and its structural, drug release, and therapeutic properties were evaluated in cellular and animal TNBC models. HSA-LAP demonstrated efficient drug loading and pH-dependent tumor-targeted release, favoring acidic tumor microenvironments. Structural and microscopic studies confirmed LAP binding to HSA, with only minor structural and no significant morphological changes observed. In 4T1 breast cancer cells, HSA-LAP exhibited superior anti-proliferative, pro-apoptotic, and anti-migratory effects compared to free LAP, which were further amplified when combined with VGB3, a VEGFR1/2-targeting peptide, indicating an effective dual-targeting strategy for TNBC. In vivo, HSA-LAP showed greater tumor inhibition and improved survival rates, especially in combination with VGB3 through apoptosis induction. Biodistribution studies using technetium-99m ( 99m Tc) labeling revealed enhanced tumor targeting. These findings highlight the potential of HSA as a delivery vehicle for LAP, particularly in combination with anti-angiogenic agents like VGB3, offering a promising therapeutic strategy for TNBC., 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 © 2024 Elsevier B.V. All rights reserved.)

The high recurrence rate of hepatocellular carcinoma (HCC) and poor prognosis after medical treatment reflects the necessity to improve the current chemotherapy protocols, particularly drug delivery methods. Development of targeted and efficient drug delivery systems (DDSs), in all active, passive and stimuli-responsive forms for selective delivery of therapeutic drugs to the tumour site has been extended to improve efficacy and reduce the severe side effects. Recent advances in nanotechnology offer promising breakthroughs in the diagnosis, treatment and monitoring of cancer cells. In this review, the specific design of DDSs based on the different nano-particles and their surface engineering is discussed. In addition, the innovative clinical studies in which nano-based DDS was used in the treatment of HCC were highlighted.

This study describes a multifunctional nanoparticle platform for targeted CT imaging and therapy of cancers. Pemetrexed (conjugated with polyethylene glycol, MW 2000 Da) and polyNIPAM (PEGylated) were designed for targeted delivery to folate receptors and thermally ablated tumors, respectively. These moieties were coated on gold nanoparticles (7 and 30 nm), and the prepared compounds were characterized using 1 H NMR, FT-IR, CHNS, DLS, TEM, TGA, and UV-vis. The resulting agents exhibited 2-4 times higher X-ray attenuation compared to Visipaque and demonstrated specific accumulation in tumor tissue (4T1 xenograft model) 90 min after injection in mice. The nanoparticles displayed anticancer activity against 4T1 and MDA-MB-231 breast cancer cells (IC 50 : 182.87 and 206.18 μg/mL) and good biocompatibility. Importantly, the platform showed excellent stability over a year and at pH 2-12 and temperature range of -78 to 40 °C, and a water-dichloromethane extraction method was optimized for efficient purification, facilitating large-scale production.

Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and sorafenib are well-known therapeutics in breast cancer. In the present study, we combined sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. The MCF-7 cells were treated with metformin, sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by real-time PCR. The results showed that MCF-7 cells treated with metformin/sorafenib and PCL-sorafenib/metformin co-treatment contributed to 50% viability compared to the untreated group. Moreover, PI and Annexin V staining tests showed that the cell viability for metformin/sorafenib and PCL-sorafenib/metformin was 38% and 17%, respectively. Furthermore, sorafenib/metformin and PCL-sorafenib/metformin lead to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2 and BAX genes and altered the cell cycle. Together, the combination of PCL-sorafenib/metformin and sorafenib/metformin increased sorafenib absorption at lower doses and also led to apoptosis and oxidative stress increases in MCF-7 cells., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Morphological modulation in covalent organic frameworks (COFs) with particular emphasis on the correlation between structure and target applications in biomedical fields, is currently in its early stage of evolution. Herein, a multifunctional rattle-architecture imine-based COF with a mobile core of gold nanoparticles (Au NPs) and an outer polydopamine (PDA) shell, tailored for cancer treatment, has been developed to effectively integrate dual responsive release capabilities with the potential for multiple therapeutic applications. The engineered COF displays outstanding crystallinity, a suitable size and precisely controlled morphological characteristics. By leveraging COF and PDA attributes, the successful co-delivery of hydrophilic doxorubicin (DOX) and hydrophobic docetaxel (DTX) within discrete compartments is achieved responsive to both pH and near-infrared triggers. Designed nanocarrier outperforms prior COFs with a superior 83.7% DOX loading capacity, thanks to its expansive internal space and porous shell. Taking advantage of the inclusion of Au core and the concurrent presence of COF and PDA outer shells, the nanocarrier exhibits a significant photothermal-conversion capability. The rattle-architecture double-shelled Au@RCOF@PDA were functionalized with poly(ethylene glycol)-folic acid (PEG-FA) to confer the system with active-targeting capability and enhanced biocompatibility. Through in vitro and in vivo evaluations, the designed system demonstrates an exceptional synergistic anti-tumor effect, along with favorable biosafety and histocompatibility. This study not only sheds light on the remarkable merits offered by regulating the morphology of COF-based systems in cancer therapy but also highlights the potential for synergistic therapeutic approaches in advancing cancer treatment strategies.

Background: Colorectal cancer (CRC), now the second most prevalent malignant tumor worldwide, is more prevalent in young adults. In recent decades, there has been progress in creating anti-colorectal cancer medications, including cytotoxic compounds., Objectives: Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of novel formulations in preventing colorectal cancer., Methods: During this study, we assessed a new kind of niosome called cyclo-Gly-L-DOPA (CG-Nio-CGLD) made from chitosan glutamate. We evaluated the anti-colorectal cancer properties of CG-Nio-CGLD utilizing CCK-8, invasion assay, MTT assay, flow cytometry, and cell cycle analysis. The transcription of genes associated with apoptosis was analyzed using quantitative real-time PCR. At the same time, the cytotoxicity of nanomaterials on both cancer and normal cell lines was assessed using MTT assays. Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of newly developed formulations in preventing colorectal cancer., Results: The Nio-CGLD and CG-Nio-CGLD were spherical mean diameters of 169.12 ± 1.87 and 179.26 ± 2.17 nm, respectively. Entrapment efficiency (EE%) measurements of the Nio-CGLD and CG-Nio-CGLD were 63.12 ± 0.51 and 76.43 ± 0.34%, respectively. In the CG-Nio-CGLD group, the percentages of early, late, necrotic, and viable CL40 cells were 341.93%, 23.27%, 9.32%, and 25.48%. The transcription of the genes PP53, cas3, and cas8 was noticeably higher in the treatment group compared to the control group (P > 0.001). Additionally, the treatment group had lower BCL2 and survivin gene expression levels than the control group (P < 0.01). Additionally, CG-Nio-CGLD formulations demonstrated a biocompatible nanoscale delivery mechanism and displayed little cytotoxicity toward the CCD 841 CoN reference cell line., Conclusion: These findings indicate that chitosan-based noisome encapsulation may enhance the effectiveness of CG-Nio-CGLD formulations in fighting cancer., (© 2024. The Author(s).)

Water-stable metal-organic frameworks based on UIO-66@NH 2 were synthesized to transport Letrozole into breast cancer cells. The UIO-66@NH 2 nanoparticles had a spherical shape and triangular base pyramid morphology, with a size range of 100-200 nm. Fourier transform infrared spectroscopy confirmed the efficient adsorption of Letrozole on UIO-66@NH 2 . The drug release profile showed a gradual, pH-dependent release of Letrozole from the nanoparticles, with a significant increase in acidic environments, indicating the adaptable release potential of UIO-66@NH 2 @Let in the breast cancer microenvironment. The size and entrapment efficiency were more stable at 4 °C than at 25 °C. To evaluate the cytotoxic effects of UIO-66@NH 2 @Let, MTT assay, gene expression analysis, flow cytometry, reactive oxygen species generation, migration assay, and DAPI staining were performed. Moreover, according to IC 50 results, the incorporation of Letrozole into UIO-66@NH 2 significantly improved its anticancer activity. The results also showed that the developed formulations induced apoptosis through both intrinsic and extrinsic pathways and inhibited cancer progression. The efficacy of the formulations in inducing apoptosis was validated by DAPI staining microscopy and flow cytometry analysis. Therefore, the Letrozole-loaded UIO-66@NH 2 MOFs developed in this study can be considered as a unique and sophisticated anticancer delivery nanosystem with promising in vitro anticancer properties., 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 © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Breast cancer continues to be a major global health challenge, driving the need for effective therapeutic strategies. Cisplatin, a powerful chemotherapeutic agent, is widely used in breast cancer treatment. However, its effectiveness is often limited by systemic toxicity and the development of drug resistance. This review examines the molecular factors that influence cisplatin response and resistance, offering crucial insights for the scientific community. It highlights the significance of understanding cisplatin resistance's genetic and epigenetic contributors, which could lead to more personalized treatment approaches. Additionally, the review explores innovative strategies to counteract cisplatin resistance, including combination therapies, nanoparticle-based drug delivery systems, and targeted therapies. These approaches are under intensive investigation and promise to enhance breast cancer treatment outcomes. This comprehensive discussion is a valuable resource to advance breast cancer therapeutics and address the challenge of cisplatin resistance., 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 © 2024 Elsevier B.V. All rights reserved.)

A comprehensive model of chemotherapy treatment of cancer can help us to optimize the drug administration/dosage and improve the treatment outcome. In the present study, a multiscale mathematical model of tumor growth during chemotherapy treatment is developed to predict its response to the medication and cancer progression. The modeling is a continuous multiscale simulation consisting of three tissue phases including cancer cells, normal cells, and extracellular matrix. In addition to the drug administration, the impacts of immune cells, programmed cell death, nutrient competition, and glucose concentration are included. The outputs of our mathematical model conform to the published experimental and clinical data, and it can be used in optimizing chemotherapy, and personalized cancer treatment.

The fluoroquinolone class of antibiotics includes derivatives of the drug ciprofloxacin. These substances have recently been advocated for the treatment of cancer. In the current study, we examined the cytotoxicity and apoptosis-inducing potential of a novel synthetic ciprofloxacin derivative in the human myeloid leukemia KG1-a cell line. With an IC 50 of 25µM, this ciprofloxacin derivative, 7-(4-(2-(benzhydryloxy)-2-oxoethyl) piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4 dihydroquinoline-3- carboxylic acid (4-BHPCP), was an active drug. Through Hoechst 33,258 staining and Annexin V/PI double staining experiments, the apoptotic activity of the 4-BHPCP was assessed morphologically. Real-time quantitative PCR was used to assess changes in the expression level of certain apoptosis-related genes, including Bcl-2, Bax, and Survivin (qRT PCR). The results of the qRT PCR analysis demonstrated that 4-BHPCP promotes apoptosis in the KG1-a cell line by down-regulating Survivin and Bcl2, up-regulating Bax, and increasing the Bax/Bcl2 transcripts in a time-dependent manner. These results imply that this novel chemical may be a promising therapy option for acute myeloid leukemia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer is one of the most serious human health issues. Drug therapy is the major common way to treat cancer. There is a growing interest in using natural compounds to overcome drug resistance, adverse reactions, and target specificity of certain types of drugs that may affect several targets with fewer side effects and be beneficial against various types of cancer. In this regard, the use of herbal medicines alone or in combination with the main anticancer drugs is commonly available. Berberine (BBR), a nature-driven phytochemical component, is a well-known nutraceutical due to its wide variety of pharmacological activities, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and hypolipidemic. In addition, BBR exerts anticancer activities. In present article, we summarized the information available on the therapeutic effects of BBR and its mechanisms on five types of the most prevalent gastrointestinal cancers, including esophageal, gastric, colorectal, hepatocarcinoma, and pancreatic cancers., (© 2023 The Authors. Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

This study involved the synthesis of a new biocompatible slow-release hydrogel named poly (acrylic acid) grafted onto sodium alginate (poly (AA-g-SA)) double network hydrogel (DNH). The hydrogel was created by polymerization of acrylic acid grafted onto sodium alginate polysaccharide using crosslinkers N,N'-methylenebisacrylamide and calcium chloride via free radical polymerization. The water absorbency of the poly (AA-g-SA) double network hydrogel was improved by optimizing the quantities of ammonium persulfate initiator, pH-sensitive monomer of acrylic acid, and crosslinkers. Various analytical techniques including attenuated total reflection Fourier-transformed infrared (ATR-FTIR), X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), thermal gravimetric analysis (TGA), field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), atomic force microscopy (AFM), and Brunauer-Emmett-Teller specific surface area analysis (BET) were used to characterize the synthesized hydrogels. The swelling and on-off switching behaviors of the hydrogels were investigated in deionized (DI) water at different temperatures and pH values. The optimum poly (AA-g-SA) DNH was tested for in vitro release of a hydrophilic chemotherapeutic drug, doxorubicin hydrochloride (DOX). The eco-friendly hydrogel favorably optimized the DOX slow release owing to its swelling rate, high absorption and regeneration capabilities. The findings of this study may have significant implications for medical and scientific research., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Cytokines are the first modern immunotherapeutic agents used for activation immunotherapy. Interleukin-18 (IL-18) has emerged as a potent anticancer immunostimulatory cytokine over the past three decades. IL-18, structurally is a stable protein with very low toxicity at biological doses. IL-18 promotes the process of antigen presentation and also enhances innate and acquired immune responses. It can induce the production of proinflammatory cytokines and increase tumor infiltration of effector immune cells to revert the immunosuppressive milieu of tumors. Furthermore, IL-18 can reduce tumorigenesis, suppress tumor angiogenesis, and induce tumor cell apoptosis. These characteristics present IL-18 as a promising option for cancer immunotherapy. Although several preclinical studies have reported the immunotherapeutic potential of IL-18, clinical trials using it as a monotherapy agent have reported disappointing results. These results may be due to some biological characteristics of IL-18. Several bioengineering approaches have been successfully used to correct its defects as a bioadjuvant. Currently, the challenge with this anticancer immunotherapeutic agent is mainly how to use its capabilities in a rational combinatorial therapy for clinical applications. The present study discussed the strengths and weaknesses of IL-18 as an immunotherapeutic agent, followed by comprehensive review of various promising bioengineering approaches that have been used to overcome its disadvantages. Finally, this study highlights the promising application of IL-18 in modern combinatorial therapies, such as chemotherapy, immune checkpoint blockade therapy, cell-based immunotherapy and cancer vaccines to guide future studies, circumventing the barriers to administration of IL-18 for clinical applications, and bring it to fruition as a potent immunotherapy agent in cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Combination therapy has been considered one of the most promising approaches for improving the therapeutic effects of anticancer drugs. This is the first study that uses two different antioxidants in full-characterized niosomal formulation and thoroughly evaluates their synergistic effects on breast cancer cells. In this study, in-silico studies of hydrophilic and hydrophobic drugs (ascorbic acid: Asc and curcumin: Cur) interactions and release were investigated and validated by a set of in vitro experiments to reveal the significant improvement in breast cancer therapy using a co-delivery approach by niosomal nanocarrier. The niosomal nanoparticles containing surfactants (Span 60 and Tween 60) and cholesterol at 2:1 M ratio were prepared through the film hydration method. A systematic evaluation of nanoniosomes was carried out. The release profile demonstrated two phases (initial burst followed by sustained release) and a pH-dependent release schedule over 72 h. The optimized niosomal preparation displayed superior storage stability for up to 2 months at 4 °C, exhibiting extremely minor changes in pharmaceutical encapsulation efficiency and size. Free dual drugs (Asc + Cur) and dual-drug loaded niosomes (Niosomal (Asc + Cur)) enhanced the apoptotic activity and cytotoxicity and inhibited cell migration which confirmed the synergistic effect of co-encapsulated drugs. Also, significant up-regulation of p53 and Bax genes was observed in cells treated with Asc + Cur and Niosomal (Asc + Cur), while the anti-apoptotic Bcl-2 gene was down-regulated. These results were in correlation with the increase in the enzyme activity of SOD, CAT, and caspase, and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) upon treatment with the mentioned drugs. Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur. Histopathological examination also revealed that Niosomal (Asc + Cur) had a lower mitosis index, invasion, and pleomorphism than Asc + Cur. These findings indicated that niosomal formulation for co-delivery of Asc and Cur would offer a promising delivery system for an effective breast cancer treatment., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Nowadays, with the advent of cutting-edge technologies in the field of biotechnology, some highly advanced medical methods are introduced to treat cancers more efficiently. In the chemotherapy processes, anti-cancer drugs can be encapsulated in a stimuli-responsive coating which is capable of being functionalized by diverse ligands to increase the biocompatibility and control drug release behavior in a targeted drug delivery system. Nanoparticles (NPs) are playing an important role as nanocarriers in chemotherapy procedures, recently, numerous novel drug delivery systems have been studied which employed diverse types of NPs with remarkable structural features like porous nanocarriers with active and extended surface areas to enhance the drug loading and delivery efficacy. In this study, Daunorubicin (DAU) as an effective anti-cancer drug for treating various cancers introduced, and its application for novel drug delivery systems either as a single chemotherapy agent or co-delivery alongside other drugs with diverse NPs has been reviewed., 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 Elsevier Masson SAS. All rights reserved.)

The rising incidence of breast cancer has been a significant source of concern in the medical community. Regarding the adverse effects and consequences of current treatments, cancers' health, and socio-economical aspects have become more complicated, leaving research aimed at improved or new treatments on top priority. Medicinal herbs contain multitarget compounds that can control cancer development and advancement. Owing to Nigella Sativa's elements, it can treat many disorders. Thymoquinone (TQ) is a natural chemical derived from the black seeds of Nigella sativa Linn proved to have anti-cancer and anti-inflammatory properties. TQ interferes in a broad spectrum of tumorigenic procedures and inhibits carcinogenesis, malignant development, invasion, migration, and angiogenesis owing to its multitargeting ability. It effectively facilitates miR-34a up-regulation, regulates the p53-dependent pathway, and suppresses Rac1 expression. TQ promotes apoptosis and controls the expression of pro- and anti-apoptotic genes. It has also been shown to diminish the phosphorylation of NF-B and IKK and decrease the metastasis and ERK1/2 and PI3K activity. We discuss TQ's cytotoxic effects for breast cancer treatment with a deep look at the relevant stimulatory or inhibitory signaling pathways. This review discusses the various forms of polymeric and non-polymeric nanocarriers (NC) and the encapsulation of TQ for increasing oral bioavailability and enhanced in vitro and in vivo efficacy of TQ-combined treatment with different chemotherapeutic agents against various breast cancer cell lines. This study can be useful to a broad scientific community, comprising pharmaceutical and biological scientists, as well as clinical investigators., Competing Interests: Declaration of Competing Interest Please declare any financial or personal interests that might be potentially viewed to influence the work presented. Interests could include consultancies, honoraria, patent ownership or other. If there are none state ‘there are none’., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: Cisplatin is a prevalent chemotherapeutic agent, and it has been used extensively to treat lung cancer. However, its clinical efficacy is hampered by its safety profile and dose-limiting toxicity. Saffron is a natural product that has shown significant anticancer effects. The combination treatment of saffron with chemotherapeutic agents has been considered a new strategy., Methods: Herein, saffron extract as a natural anticancer substance was combined with cisplatin to assess their combined efficacy against tumor development in vitro. In A549 and QU-DB cell lines, the combined effect of the saffron extract with cisplatin led to a significant reduction in cell viability as compared to cisplatin alone., Results: After 48 h incubation a considerable reduction in ROS levels in the QU-DB cell line upon treatment with cisplatin in the presence of saffron extract in comparison with cells treated with cisplatin alone. Furthermore, apoptosis increased significantly when in cells treated with cisplatin in combination with saffron extract compared to cisplatin alone., Conclusion: Our data establish that the combination of saffron extract as a natural anticancer substance with cisplatin leads to improved cell toxicity of cisplatin as an anticancer agent. Therefore, the saffron extract could be potentially used as an additive to enable a reduction in cisplatin dosages and its side effects., 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 Elsevier GmbH. All rights reserved.)

Breast cancer is a malignancy that affects mostly females and is among the most lethal types of cancer. The ligand-functionalized nanoparticles used in the nano-drug delivery system offer enormous potential for cancer treatments. This work devised a promising approach to increase drug loading efficacy and produce sustained release of 5-fluorouracil (5-FU) and Ganoderic acid (GA) as model drugs for breast cancer. Chitosan, aptamer, and carbon quantum dot (CS/Apt/COQ) hydrogels were initially synthesized as a pH-sensitive and biocompatible delivery system. Then, CS/Apt/COQ NPs loaded with 5-FU-GA were made using the W/O/W emulsification method. FT-IR, XRD, DLS, zeta potentiometer, and SEM were used to analyze NP's chemical structure, particle size, and shape. Cell viability was measured using MTT assays in vitro using the MCF-7 cell lines. Real-time PCR measured cell apoptotic gene expression. XRD and FT-IR investigations validated nanocarrier production and revealed their crystalline structure and molecular interactions. DLS showed that nanocarriers include NPs with an average size of 250.6 nm and PDI of 0.057. SEM showed their spherical form, and zeta potential studies showed an average surface charge of +37.8 mV. pH 5.4 had a highly effective and prolonged drug release profile, releasing virtually all 5-FU and GA in 48 h. Entrapment efficiency percentages for 5-FU and GA were 84.7±5.2 and 80.2 %±2.3, respectively. The 5-FU-GA-CS-CQD-Apt group induced the highest cell death, with just 57.9 % of the MCF-7 cells surviving following treatment. 5-FU and GA in CS-CQD-Apt enhanced apoptotic induction by flow cytometry. 5-FU-GA-CS-CQD-Apt also elevated Caspase 9 and downregulated Bcl2. Accordingly, the produced NPs may serve as pH-sensitive nano vehicles for the controlled release of 5-FU and GA in treating breast cancer., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Aim: This study aim to develop doxycycline within the D-α-tocopheryl polyethylene glycol 1000 succinate micelle platform as an anticancer stem cell agent. Materials & methods: The optimized nanomicelle formulation was prepared using the solvent casting method and evaluated through physicochemical and biological characterization. Results: Nanomicelles exhibited mean particle sizes of 14.48 nm (polydispersity index: 0.22) using dynamic light scattering and 18.22 nm using transmission electron micrography. Drug loading and encapsulation efficiency were 2% and 66.73%, respectively. Doxycycline-loaded micelles exhibited sustained release, with 98.5% released in 24 h. IC 50 values were 20 μg/ml for free drug and 5 μg/ml for micelles after 48 h of cell exposure. A significant 74% reduction in CD44 biomarker and 100% colony formation inhibition were observed. Conclusion: Doxycycline in hemo/biocompatible nanomicelles holds potential for ovarian cancer stem cell therapy.

Pure positive electrostatic charges (PPECs) show suppressive effect on the proliferation and metabolism of invasive cancer cells without affecting normal tissues. PPECs are used for the delivery of drug-loaded polymeric nanoparticles (DLNs) capped with negatively charged poly(lactide-co-glycolide) (PLGA) and Poly(vinyl-alcohol) PVA into the tumor site of mouse models. The charged patch is installed on top of the skin in the mouse models' tumor region, and the controlled selective release of the drug is assayed by biochemical, radiological, and histological experiments on both tumorized models and normal rats' livers. It is found that DLNs synthesized by PLGA show great attraction to PPECs due to their stable negative charges, which would not degrade immediately in blood. The burst and drug release after less than 48h of this synthesized DLNs are 10% and 50%, respectively. These compounds can deliver the loaded-drug into the tumor site with the assistance of PPECs, and the targeted-retarded release will take place. Hence, local therapy can be achieved with much lower drug concentration (conventional chemotherapy [2 mg kg -1 ] versus DLNs-based chemotherapy [0.75 mg kg -1 ]) with negligible side effects in non-targeted organs. PPECs have many potential clinical applications for advanced-targeted chemotherapy with the lowest discernible side effects., (© 2023 Wiley-VCH GmbH.)

In recent years, the anticancer properties of metabolites from halophilic microorganisms have received a lot of attention. Twenty-nine halophilic bacterial strains were selected from a culture collection to test the effects of their supernatant metabolites on stem cell-like properties of six human cancer cell lines. Human fibroblasts were used as normal control. Sphere and colony formation assay were done to assess the stem cell-like properties. invasion and migration assay, and tumor development in mice model were done to assess the anti-tumorigenesis effect in vitro and in vivo. The metabolites from Salinivenus iranica demonstrated the most potent cytotoxic effect on breast cancer cell lines (IC50 = 100 µg/mL) among all strains, with no effect on normal cells. In MDA-MB-231 cells, the supernatant metabolites enhanced both early and late apoptosis (approximately 9.5% and 48.8%, respectively) and decreased the sphere and colony formation ability of breast cancer cells. Furthermore, after intratumor injection of metabolites, tumors developed in the mice models reduced dramatically, associated with increased pro-apoptotic caspase-3 expression. The purified cytotoxic molecule, a phenol amine with a molecular weight of 1961.73 Dalton (IC50 = 1 µg/mL), downregulated pluripotency gene SRY-Box Transcription Factor 2 (SOX-2) expression in breast cancer cells which is associated with resistance to conventional anticancer treatment. In conclusion, we suggested that the phenol amine molecule from Salinivenus iranica could be a potential anti-breast cancer component., (© 2023. Springer Nature Limited.)

Galbanic acid (GBA), as a natural compound has potential anticancer properties. It has been documented that GBA shows promising therapeutic potential against various types of cancer, including breast, lung, colon, liver, and prostate cancer. Several mechanisms involve im anti-tumor effects of GBA include apoptosis induction, cell cycle arrest, inhibition of angiogenesis, suppression of metastasis, and modulation of immune responses. Furthermore, the synergistic effects of GBA along with chemotherapeutic agents led to has enhancing efficiency with reduction in toxicity. Moreover, GBA through antioxidant and anti-inflammatory properties possess indirect anti-tumor effects. In this review, we will summarize the anti-tumor effects of GBA acid along with involve mechanisms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The field of nanotechnology has introduced novel prospects for drug delivery systems, which have the potential to supplant conventional chemotherapy with reduced adverse effects. Despite being a promising porous material, ZIF-8, a metal-organic framework, tends to agglomerate in water, which limits its applicability. In order to resolve this problem, we added ZIF-8 to hydrogels consisting of gelatin and carboxymethylcellulose. This improved their mechanical strength and stability while avoiding aggregation. We utilized double emulsions with the hydrogels' biological macromolecules to construct drug carriers with enhanced control over drug release. The nanocarriers were subjected to various analytical techniques for characterization, such as Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), zeta potential, and dynamic light scattering (DLS). The findings of our study revealed that the mean size of the produced nanocarriers were 250 nm, and their zeta potential was -40.1 mV, which suggests favorable stability. The synthesized nanocarriers were found to exhibit cytotoxicity towards cancer cells, as evidenced by the results of MTT assays and flow cytometry tests. The cell viability percentage was determined to be 55 % for the prepared nanomedicine versus 70 % for the free drug. In summary, our study illustrates that the integration of ZIF-8 into hydrogels produces drug delivery systems with improved characteristics. Furthermore, the prepared nanocarriers exhibit potential for future investigation and advancement., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lung cancer is one of the deadliest cancers in the world. Introducing new promising agents can help the chemotherapeutic management of cancer. In the knowledge of oncology, plants are of special interest as a rich source of new antineoplastic and chemotherapeutic agents. Grandivittin (GRA) is one of the main constituents of Ferulago trifida Boiss. with established medicinal, phytochemical, and pharmacological properties. This study aimed to isolate and evaluate the antineoplastic potential of grandivittin and its underlying mechanisms in human lung cancer A549 cells. The viability of the A549 cells after being treated with 0.1, 0.4, 0.7, 1, and 1.3 mM of GRA for three following days was measured using the MTT method. The early apoptosis and late apoptosis were assessed by fluorescence-activated cell sorter analysis through annexin V/PI staining. The expression of apoptotic agents' genes (caspase 3, caspase 9, Bcl2, Bax, and P53) was evaluated by the RT-PCR method. GRA increased apoptotic cells and decreased cell viability in a dose- and time-dependent manner, in which only 50% of cells survived at a dose of 0.7 mM. The expression of Bax, P53, caspase 3, and caspase 9 genes in the A549 cells was significantly upregulated after GRA treatment compared to control cells (P < 0.05). On the other hand, Bcl2 was significantly downregulated after GRA treatment (P < 0.05). The results indicated that GRA can activate cell death in A549 lung carcinoma cells by inducing both DNA toxicity p53 and cascade-dependent pathways. Therefore, GRA may be a potential new therapeutic agent for the treatment of lung cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cancer, as one of the most challenging diseases of the last century, has a significant number of patients and deaths every year. Various strategies have been explored for the treatment of cancer. Chemotherapy is one of the methods of treating cancer. Doxorubicin is one of the compounds used in chemotherapy to kill cancer cells. Due to their unique properties and low toxicity, metal oxide nanoparticles are effective in combination therapy and increase the effectiveness of anti-cancer compounds. The limited in vivo circulatory period, poor solubility, and inadequate penetration of doxorubicin (DOX) restrict its use in cancer treatment, notwithstanding its attractive characteristics. It is possible to circumvent some of the difficulties in cancer therapy by using green synthesized pH-responsive nanocomposite consisting of polyvinylpyrrolidone (PVP), titanium dioxide (TiO 2 ) modified with agarose (Ag) macromolecules. TiO 2 incorporation into the PVP-Ag nanocomposite resulted in limited increased loading and encapsulation efficiencies from 41 % to 47 % and 84 % to 88.5 %, respectively. DOX diffusion among normal cells is prevented by the PVP-Ag-TiO 2 nanocarrier at pH = 7.4, though the acidic intracellular microenvironments activate the PVP-Ag-TiO 2 nanocarrier at pH = 5.4. Characterization of the nanocarrier was performed using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrophotometry, field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), and zeta potential. The average particle size and the zeta potential of the particles showed values of 349.8 nm and +57 mV, respectively. In vitro release after 96 h showed a release rate of 92 % at pH 7.4 and a release rate of 96 % at pH 5.4. Meanwhile, the initial release after 24 h was 42 % for pH 7.4 and 76 % for pH 5.4. As shown by an MTT analysis on MCF-7 cells, the toxicity of DOX-loaded PVP-Ag-TiO 2 nanocomposite was substantially greater than that of unbound DOX and PVP-Ag-TiO 2 . After integrating TiO 2 nanomaterials into the PVP-Ag-DOX nanocarrier, flow cytometry data showed a greater stimulation of cell death. These data indicate that the DOX-loaded nanocomposite is a suitable alternative for drug delivery systems., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study aims to develop sunitinib niosomal formulations and assess their in-vitro anti-cancer efficiency against lung cancer cell line, A549. Sunitinib, a highly effective anticancer drug, was loaded in the niosome with high encapsulation efficiency. Collagen was coated on the surface of the niosome for enhanced cellular uptake and prolonged circulation time. Different formulations were produced, while response surface methodology was utilized to optimize the formulations. The stability of the formulations was evaluated over a 2-month period, revealing the importance of collagen coating. MTT assay demonstrated dose-dependent cytotoxicity for all formulations against lung cancer cells. Scratch assay test suggested antiproliferative efficacy of the formulations. The flow cytometry data confirmed the improved cytotoxicity with enhanced apoptosis rate when different formulations used. The 2D fluorescent images proved the presence of drug-containing niosomes in the tumor cells. The activation of the apoptotic pathway leading to protein synthesis was confirmed using an ELISA assay, which specifically evaluated the presence of cas3 and cas7. The results of this study indicated the antiproliferative efficacy of optimized niosomal formulations and their mechanism of action. Therefore, niosomes could be utilized as a suitable carrier for delivering sunitinib into lung cancer cells, paving the way for future clinical studies., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

The application of nanoarchitectures in cancer therapy seems to be beneficial for the delivery of antitumor drugs. In recent years, attempts have been made to reverse drug resistance, one of the factors threatening the lives of cancer patients worldwide. Gold nanoparticles (GNPs) are metal nanostructures with a variety of advantageous properties, such as tunable size and shape, continuous release of chemicals, and simple surface modification. This review focuses on the application of GNPs for the delivery of chemotherapy agents in cancer therapy. Utilizing GNPs results in targeted delivery and increased intracellular accumulation. Besides, GNPs can provide a platform for the co-delivery of anticancer agents and genetic tools with chemotherapeutic compounds to exert a synergistic impact. Furthermore, GNPs can promote oxidative damage and apoptosis by triggering chemosensitivity. Due to their capacity for providing photothermal therapy, GNPs can enhance the cytotoxicity of chemotherapeutic agents against tumor cells. The pH-, redox-, and light-responsive GNPs are beneficial for drug release at the tumor site. For the selective targeting of cancer cells, surface modification of GNPs with ligands has been performed. In addition to improving cytotoxicity, GNPs can prevent the development of drug resistance in tumor cells by facilitating prolonged release and loading low concentrations of chemotherapeutics while maintaining their high antitumor activity. As described in this study, the clinical use of chemotherapeutic drug-loaded GNPs is contingent on enhancing their biocompatibility., 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 Elsevier Inc. All rights reserved.)

Drug resistance is one of the most important obstacles in effective cancer therapy triggered through various mechanisms. One of these mechanisms is caused by the upregulation of Inhibitor of Apoptosis Proteins (IAPs). IAPs, inhibit apoptosis through direct and/or indirect caspase inhibition, which themselves are antagonized by an endogenous protein called Second Mitochondrial-derived Activator of Caspases, Smac/Diablo, mediated by the presence of a tetrapeptide IAP binding motif at its N-terminus. Accordingly, Smac-based peptides are under intense investigation as anti-cancer drugs and have reached Phase 2 clinical trials, although, Smac based peptides or mimetics alone have not been effective as anti-cancer agents. On the other hand, KLA peptide has shown major toxicity against cancer cells through the induction of apoptosis. Consequently, we designed an anti-cancer chimera by fusing an octa-peptide from the N-terminus of mature Smac protein to a modified proapoptotic KLA peptide (KLAKLCKKLAKLCK) to be called Smac-KLA. This chimera, therefore, possesses both proapoptotic and anti-IAP activities. In addition, we dimerized this chimera via intermolecular disulfide bonds in order to enhance their cellular permeability. Both the Smac-KLA monomeric and dimeric peptides exhibited cytotoxic activity against both MCF-7 and MDA-MB231 breast cancer cell lines at low micromolar concentrations. Importantly, the dimerization of the chimeras enhanced their potency 2-4- fold due to higher cellular uptake., Competing Interests: Declarations of competing interest None, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Dihydrofolate reductase (DHFR) is a ubiquitous cellular enzyme involved in the biosynthesis of nucleotide and protein precursors, thus, the inhibition of human DHFR can be a promising strategy in cancer treatment. The design of effective anticancer drugs is an urgent need today according to the high spread of cancer. The indole molecule with diverse mechanisms of action and anticancer properties is one of the efficient pharmacophores in drug design. Hence, a virtual library of indole derivatives as a scaffold was selected for designing safer and more effective anticancer drugs against DHFR in this work. All indole derivatives utilized in the library design were selected regarding appreciable tumor growth inhibition. Structure-activity relationship (SAR), docking energy, ADMET (absorption, distribution, metabolism, excretion, and toxicity) parameters, and effective non-covalent interactions were used to identify potential anticancer with indole scaffold. Results showed a higher number of indole moieties provide a strong attachment to the DHFR binding pocket and therefore more effective anticancer activity. The indole scaffold in combination with dichlorobenzene improves DHFR inhibition whereas barbituric acid weakens inhibition activity. In the following to validate the docking results, Molecular dynamics (MD) simulation and molecular mechanics generalized-Born surface area (MM-GBSA) indicated the permanent stability of the selected ligands into the DHFR binding pocket and the key amino acids. Therefore, promising pharmacophores based on indole-DHFR interactions were discovered, and the outcome could be useful in guiding future in vitro and in vivo drug discovery in cancer medicine.Communicated by Ramaswamy H. Sarma.

5-Fluorouracil (5-FU) is a cytotoxic drug with a low half-life. These features can cause some problems such as burst drug release and numerous side effects. In the present study, a pH-sensitive nanocomposite of polyvinylpyrrolidone (PVP)/carboxymethyl cellulose (CMC)/γ-alumina developed by using water in oil in water (W/O/W) double emulsion method. The fabricated emulsion has been employed as the 5-FU carrier to investigate its effects on drug half-life, side effects, drug loading efficiency (DLE), and drug entrapment efficiency (DEE). Analyzing the FTIR and XRD indicated the successful loading of 5-FU into the nanocarrier and affirmed the synthesized nanocomposite's chemical bonding and crystalline features. Furthermore, by using DLS and Zeta potential assessment, size and undersize distribution, as well as the stability of the drug-loaded nanocomposite were determined, which demonstrated the monodisperse and stable nanoparticles. Moreover, the nanocomposites with spherical shapes and homogeneous surfaces were shown in FE-SEM, which indicated good compatibility for the constituents of the nanocomposites. Moreover, by employing BET analysis the porosity has been investigated. Drug release pattern was studied, which indicated a controlled drug release behavior with above 96 h drug retention. Besides, the loading and entrapment efficiencies were obtained 44 % and 86 %, respectively. Furthermore, the curve fitting technique has been employed and the predominant release mechanism has been determined to evaluate the best-fitted kinetic models. MTT assay and flow cytometry assessment has been carried out to investigate the cytotoxic effects of the fabricated drug-loaded nanocomposite on MCF-7 and normal cells. The results showed enhanced cytotoxicity and late apoptosis for the PVP/CMC/γ-alumina/5-FU. Based on the MTT assay outcomes on normal cell lines (L929), which indicated above 90 % cell viability, the biocompatibility and biosafety of the synthesized nanocarrier have been confirmed. Moreover, due to the porosity of the PVP/CMC/γ-alumina, this nanocarrier can exploit from high specific surface area and be more sensitive to environmental conditions such as pH. These outcomes propose that the novel pH-sensitive PVP/CMC/γ-alumina nanocomposite can be a potential candidate for drug delivery applications, especially for cancer therapy., 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.)

Breast cancer is a collation of malignancies that manifest in the mammary glands at the early stages. Among breast cancer subtypes, triple-negative breast cancer (TNBC) shows the most aggressive behavior, with apparent stemness features. Owing to the lack of response to hormone therapy and specific targeted therapies, chemotherapy remains the first line of the TNBC treatment. However, the acquisition of resistance to chemotherapeutic agents increase therapy failure, and promotes cancer recurrence and distant metastasis. Invasive primary tumors are the birthplace of cancer burden, though metastasis is a key attribute of TNBC-associated morbidity and mortality. Targeting the chemoresistant metastases-initiating cells via specific therapeutic agents with affinity to the upregulated molecular targets is a promising step in the TNBC clinical management. Exploring the capacity of peptides as biocompatible entities with the specificity of action, low immunogenicity, and robust efficacy provides a principle for designing peptide-based drugs capable of increasing the efficacy of current chemotherapy agents for selective targeting of the drug-tolerant TNBC cells. Here, we first focus on the resistance mechanisms that TNBC cells acquire to evade the effect of chemotherapeutic agents. Next, the novel therapeutic approaches employing tumor-targeting peptides to exploit the mechanisms of drug resistance in chemorefractory TNBC are described., 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 Elsevier Inc. All rights reserved.)

Although quercetin (QC) has valuable advantages, its low water solubility and poor permeability have limited its utilization as an anticancer drug. In this study, hydrogel nanocomposite of chitosan (CS), halloysite (HNT), and graphitic‑carbon nitride (g-C3N4) was prepared and loaded by QC using a water in oil in water emulsification process to attain QC sustained-release. Using g-C3N4 in the HNT/CS hydrogel solution enhanced the entrapment effectiveness (EE %) by up to 86 %. The interactions between QC and nanoparticles caused the nanocomposite pH-responsive behavior that assists in minimizing the side effect of the anticancer agent by controlling the burst release of QC at neutral conditions. According to DLS analysis, the size of the QC-loaded nanovehicle was 454.65 nm, showing that nanoparticles are highly monodispersed, which also was approved by FE-SEM. Additionally, Zeta potential value for the fabricated drug-loaded nanocarrier is +55.23 mV displaying that nanoparticles have good stability. The hydrogel nanocomposite structure's completeness was shown by FTIR pattern, and quercetin was included into the designed delivery system based on XRD data. Besides, the drug release profile indicated that a targeted sustained-release and pH-sensitive release of anticancer drug with the 96-hour extended-release were noticed. In order to comprehend the process of QC release at pH 5.4 and 7.4, four kinetic models were employed to find the best-suited model according to the acquired release data. Finally, the MTT experiment revealed considerable cytotoxicity against breast cancer cells, MCF-7 cell line was experimented in vitro, for the CS/HNT/g-C3N4 targeted delivery system in comparison to QC as a free drug. According to the above description, the CS/HNT/g-C3N4 delivery platform is a unique pH-sensitive drug delivery system for anticancer purposes that improves loading as well as sustained-release of quercetin., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

5-Fluorouracil (5-FU) is amongst the most commonly used antimetabolite chemotherapeutic agents in recent decades. However, its low bioavailability, short half-life, rapid metabolism and the development of drug resistance after chemotherapy limit its therapeutic efficiency. In this study, 5-FU applications as an anti-cancer drug for treating diverse types of cancers (e.g. colon, pancreatic and breast) have been reviewed. Different approaches lately designed to circumvent the drawbacks of 5-FU therapy are described herein, including 5-FU-loaded lipid-based nanoparticles (NPs), polymeric NPs (both stimuli and non-stimuli responsive), carbon-based nanostructures and inorganic NPs. Furthermore, co-delivery systems of 5-FU with other drugs (e.g. paclitaxel, gelatin-doxorubicin and naproxen) have been reviewed, which aid to attain better bioavailability, higher effectiveness at a lower concentration and lower toxicity. This review provides researchers with the latest progress on 5-FU-loaded nanocarriers, which show great potential as an advanced tool for cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Anti-VEGF therapies are common for the treatment of cancer. Carboxypeptidase G (CPG-2) enzyme is a zinc-dependent metalloenzyme that metabolizes non-toxic synthetic 'benzoic mustard prodrugs' to cytotoxic moieties in tumor cells. In this study, we designed a dual-activity agent by combining a designed anti-VEGF- and CPG-2 enzyme to convert methotrexate (MTX). VEGF-A was docked against a set of scaffolds, and suitable inverse rotamers were made. Rosetta design was used for the interface design. The top 1200 binders were chosen by flow cytometry and displayed in yeast. The activity of CPG-2 enzyme was analyzed at different temperature conditions and in the presence of the substrate, MTX. Optimal binders were selected and protein was eluted using immobilized metal affinity chromatography and size-exclusion chromatography. Both, native PAGE and on-yeast flow cytometry confirmed the binding of the binder to VEGF-A. The activity of truncated enzymes was slightly lower than that of full-length enzymes linked to VEGF-A. The method should be generally useful as a dual-activity agent for targeting VEGF-A and combination therapy with the enzyme CPG-2 for metabolizing non-toxic prodrugs to cytotoxic moieties.Communicated by Ramaswamy H. Sarma.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1 or CD279) have noticeably improved the treatment landscape of advanced cancer patients. Nivolumab, the most well-known genetically engineered anti-PD-1 monoclonal antibody (mAb), promotes anti-tumor immunity and shows excellent capability for treating various cancers, particularly lung cancer, renal cancer, and melanoma. Systemic administration of nivolumab could inspire durable therapeutic responses not typically seen with traditional cytotoxic anti-cancer agents. However, nivolumab monotherapy is ineffective in 60-70 percent of patients. The mechanisms leading to both primary and acquired resistance to PD-1/PD-L1 inhibition are varied and multifactorial. Recently, the rationality of adding other conventional therapies such as chemo-radiotherapy and targeted therapies such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and VEGF/VEGFR inhibitors to nivolumab has strongly been verified. These regimens overcome cancer resistance and thus boost nivolumab efficacy in cancer patients. Herein, we discuss the current status of the combination therapy with nivolumab in cancer patients, with a particular focus on the recent clinical reports., 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 © 2022 Elsevier B.V. All rights reserved.)

One of the malignant tumors in women that has involved both developed and developing countries is breast cancer. Similar to other types of tumors, breast cancer cells demonstrate high metastatic nature. Besides, breast tumor cells have ability of developing drug resistance. EMT is the related mechanism to cancer metastasis and focus of current manuscript is highlighting function of EMT in breast tumor malignancy and drug resistance. Breast tumor cells increase their migration by EMT induction During EMT, N-cadherin and vimentin levels increase, and E-cadherin levels decrease to mediate EMT-induced breast tumor invasion. Different kinds of anti-cancer agents such as tamoxifen, cisplatin and paclitaxel that EMT induction mediates chemoresistance feature of breast tumor cells. Furthermore, EMT induction correlates with radio-resistance in breast tumor. Clinical aspect is reversing EMT in preventing chemotherapy or radiotherapy failure in breast cancer patients and improving their survival time. The anti-tumor agents that suppress EMT can be used for decreasing breast cancer invasion and increasing chemosensitivity of tumor cells. Furthermore, lncRNAs, miRNAs and other factors can modulate EMT in breast tumor progression that are discussed here., Competing Interests: Conflict of interest statement Authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The site-specific delivery of antitumor agents is of importance for providing effective cancer suppression. Poor bioavailability of anticancer compounds and the presence of biological barriers prevent their accumulation in tumor sites. These obstacles can be overcome using liposomal nanostructures. The challenges in cancer chemotherapy and stimuli-responsive nanocarriers are first described in the current review. Then, stimuli-responsive liposomes including pH-, redox-, enzyme-, light-, thermo- and magneto-sensitive nanoparticles are discussed and their potential for delivery of anticancer drugs is emphasized. The pH- or redox-sensitive liposomes are based on internal stimulus and release drug in response to a mildly acidic pH and GSH, respectively. The pH-sensitive liposomes can mediate endosomal escape via proton sponge. The multifunctional liposomes responsive to both redox and pH have more capacity in drug release at tumor site compared to pH- or redox-sensitive alone. The magnetic field and NIR irradiation can be exploited for external stimulation of liposomes. The light-responsive liposomes release drugs when they are exposed to irradiation; thermosensitive-liposomes release drugs at a temperature of &gt;40 °C when there is hyperthermia; magneto-responsive liposomes release drugs in presence of magnetic field. These smart nanoliposomes also mediate co-delivery of drugs and genes in synergistic cancer therapy. Due to lack of long-term toxicity of liposomes, they can be utilized in near future for treatment of cancer patients., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Breast cancer (BC) is one of the most common cancers in females and is responsible for the highest cancer-related deaths following lung cancer. The complex tumor microenvironment and the aggressive behavior, heterogenous nature, high proliferation rate, and ability to resist treatment are the most well-known features of BC. Accordingly, it is critical to find an effective therapeutic agent to overcome these deleterious features of BC. Resveratrol (RES) is a polyphenol and can be found in common foods, such as pistachios, peanuts, bilberries, blueberries, and grapes. It has been used as a therapeutic agent for various diseases, such as diabetes, cardiovascular diseases, inflammation, and cancer. The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis. In addition, the synergistic effects of RES in combination with other chemotherapeutic agents, such as docetaxel, paclitaxel, cisplatin, and/or doxorubicin may contribute to enhancing the anticancer properties of RES on BC cells. Although, it demonstrates promising therapeutic features, the low water solubility of RES limits its use, suggesting the use of delivery systems to improve its bioavailability. Several types of nano drug delivery systems have therefore been introduced as good candidates for RES delivery. Due to RES's promising potential as a chemopreventive and chemotherapeutic agent for BC, this review aims to explore the anticancer mechanisms of RES using the most up to date research and addresses the effects of using nanomaterials as delivery systems to improve the anticancer properties of RES., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Recently, nanotechnology is involved in various fields of science, of which medicine is one of the most obvious. The use of nanoparticles in the process of treating and diagnosing diseases has created a novel way of therapeutic strategies with effective mechanisms of action. Also, due to the remarkable progress of personalized medicine, the effort is to reduce the side effects of treatment paths as much as possible and to provide targeted treatments. Therefore, the targeted delivery of drugs is important in different diseases, especially in patients who receive combined drugs, because the delivery of different drug structures requires different systems so that there is no change in the drug and its effectiveness. Niosomes are polymeric nanoparticles that show favorable characteristics in drug delivery. In addition to biocompatibility and high absorption, these nanoparticles also provide the possibility of reducing the drug dosage and targeting the release of drugs, as well as the delivery of both hydrophilic and lipophilic drugs by Niosome vesicles. Since various factors such as components, preparation, and optimization methods are effective in the size and formation of niosomal structures, in this review, the characteristics related to niosome vesicles were first examined and then the in silico tools for designing, prediction, and optimization were explained. Finally, anticancer drugs delivered by niosomes were compared and discussed to be a suitable model for designing therapeutic strategies. In this research, it has been tried to examine all the aspects required for drug delivery engineering using niosomes and finally, by presenting clinical examples of the use of these nanocarriers in cancer, its clinical characteristics were also expressed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Herein, UiO-66 and its two functional analogs (with -NO 2 and -NH 2 functional groups) were synthesized, and their potential ability as pH stimulus nanocarriers of quercetin (QU), an anticancer agent, was studied. UiO-66 is a low-toxicity, biocompatible metal-organic framework with a large surface area and good stability, which can be prepared through a facile and inexpensive method. Before and after drug loading, various analyses were conducted to characterize the synthesized nanocarriers. Moreover, Monte Carlo simulations were performed to investigate their structures and interactions with quercetin. The most promising drug loading potential and prolonged drug release (over 25 days) were observed in QU@UiO-66-NO 2 with 37% drug loading content, which was the best-tested sample that exhibited a higher release rate under acidic conditions (pH = 5) than that in normal cells (pH = 7.4). This behavior is known as pH-stimulus-controlled ability. The cell treatment with free QU, UiO-66-R, and QU@UiO-66-R (R = -H, -NO 2 , and -NH 2 ) was performed, and an MTT assay was conducted on HEK-293 and MDA-MB-231 cells for the cytotoxicity study. Additionally, the kinetic modeling of drug release was investigated on the basis of the analysis of the drug release profiles.

Curcumin application as an anti-cancer drug is faced with several impediments. This study has developed a platform that facilitates the sustained release of curcumin, improves loading efficiency, and anti-cancer activity. Montmorillonite (MMT) nanoparticles were added to chitosan (CS)-agarose (Aga) hydrogel and then loaded with curcumin (Cur) to prepare a curcumin-loaded nanocomposite hydrogel. The loading capacity increased from 63% to 76% by adding MMT nanoparticles to a chitosan-agarose hydrogel. Loading the fabricated nanocomposite in the nanoniosomal emulsion resulted in sustained release of curcumin under acidic conditions. Release kinetics analysis showed diffusion and erosion are the dominant release mechanisms, indicating non-fickian (or anomalous) transport based on the Korsmeyer-Peppas model. FTIR spectra confirmed that all nanocomposite components were present in the fabricated nanocomposite. Besides, XRD results corroborated the amorphous structure of the prepared nanocomposite. Zeta potential results corroborated the stability of the fabricated nanocarrier. Cytotoxicity of the prepared CS-Aga-MMT-Cur on MCF-7 cells was comparable with that of curcumin-treated cells (p < 0.001). Moreover, the percentage of apoptotic cells increased due to the enhanced release profile resulting from the addition of MMT to the hydrogel and the incorporation of the fabricated nanocomposite into the nanoniosomal emulsion. To recapitulate, the current delivery platform improved loading, sustained release, and curcumin anti-cancer effect. Hence, this platform could be a potential candidate to mitigate cancer therapy restrictions with curcumin., (© 2022 American Institute of Chemical Engineers.)

Five previously unreported terpenoids, together with fifteen known analogs, were isolated from a methanol extract of the roots and rhizomes of Nardostachys jatamansi. Their structures, including absolute configurations, were elucidated by spectroscopic data and electronic circular dichroism (ECD) spectra analyses, as well as single-crystal X-ray diffraction for crystalline compounds. Structurally, (4R,5S,6S,7R)-1(10)-aristolane-8,9-diacid is a novel 8,9-dicarboxylic acid derivative of aristolane-type sesquiterpenoid. (4R,6S,7R,10S)-10-Hydroxyguaia-1(5)-6,7-epoxy-2-one is an undescribed analogue of nardoguaianone K, with a rare 6,7-epoxide group. (4R,5R,6R,8R)-1(10)-Isonardosinone-8-ol-9-one-7,11-lactone is an isonardosinane-type sesquiterpene bearing a γ-lactone ring. Dinardokanshone F is a rare example of a sesquiterpene dimer from N. jatamansi connected by an oxo bridge. The isolates were evaluated for their cytotoxic activity against four human pancreatic cancer cell lines (CFPAC-1, PANC-1, CAPAN-2 and SW1990). Compound epoxynardosinone exhibited significant cytotoxicity against CAPAN-2 cell lines with IC 50 value of 2.60 ± 1.85 μM. 1-Hydroxylaristolone displayed comparable cytotoxicity on CFPAC-1 cell lines (IC 50 1.12 ± 1.19 μM), compared to Taxol (IC 50 0.32 ± 0.13 μM). 1-Hydroxylaristolone, 1(10)-aristolane-9β-ol, 1(10)-aristolen-2-one, alpinenone, valtrate isovaleroyloxyhydrine and nardostachin displayed stronger cytotoxicity against PANC-1 cell lines with IC 50 values ranging from 0.01 ± 0.01 to 6.50 ± 1.10 μM. 1(10)-Aristolane-9β-ol, 10-hydroxyguaia-1(5)-6,7-epoxy-2-one, nardoguaianone K, nardonoxide, epoxynardosinone, 1(10)-isonardosinone-8-ol-9-one-7,11-lactone, valtrate isovaleroyloxyhydrine and nardostachin showed remarkable cytotoxicity against SW1990 cell lines with IC 50 values ranging from 0.07 ± 0.05 to 4.82 ± 6.96 μM. Furthermore, the primary mechanistic study of nardostachin demonstrated that it induced cell apoptosis via the mitochondria-dependent pathway, and induced SW1900 cell arrest at G2/M phase., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Enhancing the therapeutic profile of hydrophobic drugs using the development of biocompatible drug delivery systems is an urgent need. Many types of research have been conducted on graphene derivatives owing to their unique characteristics., Methods: In this survey, quercetin (QUER), a natural medicine, was loaded on carboxylated graphene oxide (GO), and cytotoxicity assay and the uptake of QUER into prostate cancer cells (PC3) were evaluated., Results: The release behavior of QUER was temperature- and pH-sensitive. Although QUER was loaded with high efficiency, the released rate was low (23.25% at pH 5.5 and 42 °C). The toxicity and intensity of fluorescence in the FREE QUER were higher than the loaded form., Conclusion: High-capacity loading and controlled release of GO QUER can be recognized as a proper candidate in treating cancer.

Background: In this study, the optimized niosomal formulation containing paclitaxel using non-ionic surfactants and cholesterol was designed and its cytotoxic effects against different breast cancer cell lines and apoptosis gene expression analysis were also investigated., Methods and Results: Due to enhancing equation variables, the Box-Behnken method has been applied. Lipid/drug molar ratio, the amounts of Span 60, and cholesterol were selected as the target for optimization. The particle size of niosome loaded paclitaxel and entrapment efficiency proportion have been considered in the role of dependent variables. Then the cytotoxic activity of the optimized formulation was evaluated using an MTT assay against different breast cancer cell lines including MCF-7, T-47D, SkBr3, and MDA-MB-231. The expression level of Bax and Bcl-2 apoptosis genes was determined by Real-Time PCR. In this study, the optimized niosomal formulation revealed that the synthesized niosomes had a spherical appearance and had an average size of 192.73 ± 5.50 nm so that the percentage of drug loading was 94.71 ± 1.56%. Moreover, this formulation showed a controlled and slowed release of paclitaxel at different pH (7.4, 6.5, and 5.4). The cytotoxicity results demonstrated that cell viability in all concentrations of niosome loaded paclitaxel had profound cytotoxic effects on all studied breast cancer cell lines compared to the free paclitaxel (p < 0.05). In addition, the expression of apoptosis genes was much higher than that of free paclitaxel indicating the susceptibility of cells to apoptosis., Conclusions: As a result, niosomal formulations containing paclitaxel can be used as a new drug delivery system to increase cytotoxicity and treatment of breast cancer in the upcoming future., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The novel pH-responsive polymer nanoparticles have been widely used for drug delivery and cancer therapy. The pH-sensitive nanoparticles include chemical structures that can accept or donate protons in response to an environmental pH change. Polybases which mostly contain alkaline groups such as amines and hydroxy, accept protons at low pH and are neutral at higher pH values. This study aimed to prepare pH-sensitive colloidal amphiphilic poly(vinyl alcohol-2-hydroxyethyl methacrylate) (PVA-PHEMA) copolymers in cancer therapy applications. For this purpose, poly(vinyl acetate-2-hydroxyethyl methacrylate) (PVAc-PHEMA) copolymer nanoparticles were synthesized in different polymerization medium fractions from water and methanol and different monomer feed concentration. Then acetate groups were hydrolyzed, and the PHEMA-PVA nanoparticles were synthesized. The nanoparticles were further characterized using dynamic light scattering, Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis to identify the structural and morphological changes. The Methotrexate (MTX) was loaded into the nanoparticles, and drug release kinetics were evaluated. The results confirmed that PHEMA-PVA copolymeric nanoparticles could be favorably used in cancer therapy., (© 2022 IOP Publishing Ltd.)

Synthetic lethal interactions, where the simultaneous but not individual inactivation of two genes is lethal to the cell, have been successfully exploited to treat cancer. GATA3 is frequently mutated in estrogen receptor (ER)-positive breast cancers and its deficiency defines a subset of patients with poor response to hormonal therapy and poor prognosis. However, GATA3 is not yet targetable. Here we show that GATA3 and MDM2 are synthetically lethal in ER-positive breast cancer. Depletion and pharmacological inhibition of MDM2 significantly impaired tumor growth in GATA3-deficient models in vitro, in vivo and in patient-derived organoids/xenograft (PDOs/PDX) harboring GATA3 somatic mutations. The synthetic lethality requires p53 and acts via the PI3K/Akt/mTOR pathway. Our results present MDM2 as a therapeutic target in the substantial cohort of ER-positive, GATA3-mutant breast cancer patients. With MDM2 inhibitors widely available, our findings can be rapidly translated into clinical trials to evaluate in-patient efficacy., (© 2022. The Author(s).)

Background: Tubulin inhibitors have proved to be a promising treatment against cancer. Tubulin inhibitors target different areas in microtubule structure to exert their effects. The colchicine binding site (CBS) is one of them for which there is no FDA-approved drug yet. This makes CBS a desirable target for drug design., Methods: Primary virtual screening is done by developing a possible pharmacophore model of colchicine binding site inhibitors of tubulins, and 2,3-diphenylquinoxaline is chosen as a lead compound to synthesis. In this study, 28 derivatives of 2,3-diphenylquinoxalines are synthesized, and their cytotoxicity is evaluated by the MTT assay in different human cancer cell lines, including AGS (Adenocarcinoma gastric cell line), HT-29 (Human colorectal adenocarcinoma cell line), NIH3T3 (Fibroblast cell line), and MCF-7 (Human breast cancer cell)., Results: Furthermore, the activity of the studied compounds was investigated using computational methods involving molecular docking of the 2,3-diphenylquinoxaline derivatives to β-tubulin. The results showed that the compounds with electron donor functionalities in positions 2 and 3 and electron-withdrawing groups in position 6 are the most active tubulin inhibitors., Conclusion: Apart from the high activity of the synthesized compounds, the advantage of this report is the ease of the synthesis, work-up, and isolation of the products in safe, effective, and high-quality isolated yields., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer stem cells (CSCs) play an essential role in cancer development, metastasis, relapse, and resistance to treatment. In this article, the effects of three synthesized ZnO nanofluids on proliferation, apoptosis, and stemness markers of breast cancer stem-like cells are reported. The antiproliferative and apoptotic properties of ZnO nanoparticles were evaluated on breast cancer stem-like cell-enriched mammospheres by MTS assay and flowcytometry, respectively. The expression of stemness markers, including WNT1, NOTCH1, β-catenin, CXCR4, SOX2, and ALDH3A1 was assessed by real-time PCR. Western blotting was used to analyze the phosphorylation of Janus kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3). Markers of stemness were significantly decreased by ZnO nanofluids, especially sample (c) with code ZnO-148 with a different order of addition of polyethylene glycol solution at the end of formulation, which considerably decreased all the markers compared to the controls. All the studied ZnO nanofluids considerably reduced viability and induced apoptosis of spheroidal and parental cells, with ZnO-148 presenting the most effective activity. Using CD95L as a death ligand and ZB4 as an extrinsic apoptotic pathway blocker, it was revealed that none of the nanoparticles induced apoptosis through the extrinsic pathway. Results also showed a marked inhibition of the JAK/STAT pathway by ZnO nanoparticles; confirmed by downregulation of Mcl-1 and Bcl-XL expression. The present data demonstrated that ZnO nanofluids could combat breast CSCs via decreasing stemness markers, stimulating apoptosis, and suppressing JAK/STAT activity., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Curcumin is a phytochemical isolated from Curcuma longa with potent tumor-suppressor activity, which has shown significant efficacy in pre-clinical and clinical studies. Curcumin stimulates cell death, triggers cycle arrest, and suppresses oncogenic pathways, thereby suppressing cancer progression. Cisplatin (CP) stimulates DNA damage and apoptosis in cancer chemotherapy. However, CP has adverse effects on several organs of the body, and drug resistance is frequently observed. The purpose of the present review is to show the function of curcumin in decreasing CP's adverse impacts and improving its antitumor activity. Curcumin administration reduces ROS levels to prevent apoptosis in normal cells. Furthermore, curcumin can inhibit inflammation via down-regulation of NF-κB to maintain the normal function of organs. Curcumin and its nanoformulations can reduce the hepatoxicity, neurotoxicity, renal toxicity, ototoxicity, and cardiotoxicity caused by CP. Notably, curcumin potentiates CP cytotoxicity via mediating cell death and cycle arrest. Besides, curcumin suppresses the STAT3 and NF-ĸB as tumor-promoting pathways, to enhance CP sensitivity and prevent drug resistance. The targeted delivery of curcumin and CP to tumor cells can be mediated nanostructures. In addition, curcumin derivatives are also able to reduce CP-mediated side effects, and increase CP cytotoxicity against various cancer types., (© 2021 John Wiley & Sons Ltd.)