Natural Killer Cell Defects in Breast Cancer: A Key Pathway for Tumor Evasion

As the most important innate immune component cancers invader, natural killer (NK) cells have a magnificent role in antitumor immunity without any prior sensitization. Different subsets of NK cells have distinct responses during tumor cell exposure, according to their phenotypes and environments. Their function is induced mainly by the activity of both inhibitory and activating receptors against cancerous cells. Since the immunosuppression in the tumor microenvironment of breast cancer patients has directly deteriorated the phenotype and disturbed the function of NK cells, recruiting compensatory mechanisms indicate promising outcomes for immunotherapeutic approaches. These evidences accentuate the importance of NK cell distinct features in protection against breast tumors. In this review, we discuss the several mechanisms involved in NK cells suppression which consequently promote tumor progression and disease recurrence in patients with breast cancer. © 2020 Taylor & Francis Group, LLC

Recent advances in development of nano-carriers for immunogene therapy in various complex disorders

Immunotherapy is a novel preference for the treatment of various complex diseases. Considering the application of varying agents for suppression or activation of the immune system, immunogene therapy was confirmed to stand as a proper alternative for other immunotherapeutic strategies due to its capability in targeting cells with more specificity that leads to controlling the expression of therapeutic genes. This method facilitates the local and single-dose application of most gene therapies that result in the usage of high therapeutic doses with a low risk of systemic side effects while being cost-efficient in long-term administrations. However, the existing barriers between the administration site and cell nucleus limited the clinical uses of genetic materials. These challenges can be overcome through the promising method of exerting non-carriers with high stability, low toxicity/immunogenicity, and simple modifications. In this study, we attempted to review the potential of nanoparticle application throughout the immunogene therapy of different diseases including cancer, microbial diseases, allergies, inflammatory bowel disease, rheumatoid arthritis, and respiratory infections. We included the outline of some challenges and opportunities in regards to the delivery of genetic materials that are based on nano-systems through immunotherapy of these disorders. Next to the promising future of these vectors, more detailed analyses are required to overcome the current limitations in clinical approaches. © 2022 Mashhad University of Medical Sciences. All rights reserved

Improved anticancer efficiency of Mitoxantrone by Curcumin loaded PLGA nanoparticles targeted with AS1411 aptamer

Objective(s): Mitoxantrone (MTX) is one of the most commonly used chemotherapeutic agents for treatment of different cancers. However, prolonged treatment with MTX results in unwanted side effects and drug resistant cancer cells. Combination therapies and exploiting of targeted nanoparticles have the potential of improving the efficiency of drug treatment as well as reducing the side effects. Curcumin (CUR) is a biological molecules with anticancer property. In this study, we investigated whether targeted PLGA (Poly Lactic-co-Glycolic Acid)-CUR nanoparticles (NPs) can reinforce the effect of MTX on breast cancer cells. Materials and Methods: PLGA NPs containing CUR targeted with AS1411 aptamer were prepared by single emulsion evaporation method. Physicochemical properties of NPs were investigated. The cytotoxicity of non-targeted and targeted NPs along with MTX was evaluated on MCF7, 4T1 and L929 cell lines. Results: The results showed that PLGA-CUR NPs were synthetized with an average encapsulation efficiency of 66 with a mean size of 18

Targeted delivery of galbanic acid to colon cancer cells by PLGA nanoparticles incorporated into human mesenchymal stem cells

Objective: The aim of this study was to investigate the efficacy of mesenchyme stem cells (MSCs) derived from human adipose tissue (hMSCs) as carriers for delivery of galbanic acid (GBA), a potential anticancer agent, loaded into poly (lactic-co-glycolic acid) (PLGA) nanoparticles (nano-engineered hMSCs) against tumor cells. Materials and Methods: GBA-loaded PLGA nanoparticles (PLGA/GBA) were prepared by single emulsion method and their physicochemical properties were evaluated. Then, PLGA/GBA nanoparticles were incorporated into hMSCs (hMSC/PLGA-GBA) and their migration ability and cytotoxicity against colon cancer cells were investigated. Results: The loading efficiency of PLGA/GBA nanoparticles with average size of 214±30.5 nm into hMSCs, was about 85 and 92 at GBA concentration of 20 and 40 μM, respectively. Nano-engineered hMSCs showed significant higher migration to cancer cells (C26) compared to normal cells (NIH/3T3). Furthermore, nano-engineered hMSCs could effectively induce cell death in C26 cells in comparison with non-engineered hMSCs. Conclusion: hMSCs could be implemented for efficient loading of PLGA/GBA nanoparticles to produce a targeted cellular carrier against cancer cells. Thus, according to minimal toxicity on normal cells, it deserves to be considered as a valuable platform for drug delivery in cancer therapy. © 2022 Mashhad University of Medical Sciences. All rights reserved

Immune responses modulation by curcumin and allergen encapsulated into PLGA nanoparticles in mice model of rhinitis allergic through sublingual immunotherapy

The purpose of this study was the combination of curcumin and ovalbumin in free form or encapsulated into PLGA NPs (polylactic co-glycolic acid nanoparticles) to enhance their sublingual immunotherapy (SLIT) efficiency in mouse model of rhinitis allergic. PLGA NPs containing curcumin (CUR), ovalbumin (OVA) or both were prepared by emulsion-solvent evaporation method and characterized. After sensitization of BALB/C mice with ovalbumin, SLIT with free or encapsulated formulations was carried out and immunological profiles were evaluated. SLIT treatment with all synthesized PLGA formulations lead to significantly decreased total IgE. The combination immunotherapy in the present of free form of curcumin or ovalbumin with encapsulated forms of the another substance (P.OVA-CUR 10 and P.CUR 5-OVA), showed the highest level of IFN-γ:IL-4 compared to other target groups. On the other hands, a significant increasment was observed in this ratio between these optimal groups and treated group with subcutaneous administration of OVA as the most commonly used method for immunotherapy. The study of nasal lavage fluid (NALF) showed significant decreased levels of total and eosinophil cell count in the traeted nano-formulation groups. The histopathological results of NAL were also like normal with no cellular infiltration and no inflammation in the optimal formulations. Therefore, using curcumin and nanoparticles with allergen can be considerd as potential immune modulatory agents. © 2020 Elsevier B.V