RESUMO
These days carbon dots have been developed for multiple biomedical applications. In the current study, the transfection potential of synthesized carbon dots from single biopolymers such as chitosan, PEI-2kDa, and PEI-25kDa (CS-CDs, PEI2-CDs, and PEI25-CDs) and by combining two biopolymers (CP2-CDs and CP25-CDs) through a bottom-up approach have been investigated. The characterization studies revealed successful synthesis of fluorescent, positively charged carbon dots <20 nm in size. Synthesized carbon dots formed a stable complex with plasmid DNA (EGFP-N1) and miRNA-153 that protected DNA/miRNA from serum-induced degradation. In-vitro cytotoxicity analysis revealed minimal cytotoxicity in cancer cell lines (A549 and MDA-MB-231). In-vitro transfection of EGFP-N1 plasmid DNA with PEI2-CDs, PEI25-CDs and CP25-CDs demonstrated that these CDs could strongly transfect A549 and MDA-MB-231 cells. The highest EGFP-N1 plasmid transfection efficiency was observed with PEI2-CDs at a weight ratio of 32:1. PEI25-CDs polyplex showed maximum transfection at a weight ratio of 8:1 in A549 at a weight ratio of 16:1 in MDA-MB-231 cells. CP25-CDs exhibited the highest transfection at a weight ratio of 16:1 in both cell lines. The in-vitro transfection of target miRNA, i.e., miR-153 in A549 and MDA-MB-231 cells with PEI2-CDs, PEI25-CDs, and CP25-CDs suggested successful transfer of miR-153 into cells which induced significant cell death in both cell lines. Importantly, CS-CDs and CP2-CDs could be tolerated by cells up to 200 µg/mL concentration, while PEI2-CDs, PEI25-CDs, and CP25-CDs showed non-cytotoxic behavior at low concentrations (25 µg/mL). Together, these results suggest that a combination of carbon dots synthesized from chitosan and PEI (CP25-CDs) could be a novel vector for transfection nucleic acids that can be utilized in cancer therapy.
RESUMO
Cancer immunotherapy has emerged as a promising strategy for the treatment of many forms of cancer by stimulating body's own immune system. This therapy not only eradicates tumor cells by inducing strong anti-tumor immune response but also prevent their recurrence. The clinical cancer immunotherapy faces some insurmountable challenges including high immune-mediated toxicity, lack of effective and targeted delivery of cancer antigens to immune cells and off-target side effects. However, nanotechnology offers some solutions to overcome those limitations, and thus can potentiate the efficacy of immunotherapy. This review focuses on the advancement of nanoparticle-mediated delivery of immunostimulating agents for efficient cancer immunotherapy. Here we have outlined the use of the immunostimulatory nanoparticles as a smart carrier for effective delivery of cancer antigens and adjuvants, type of interactions between nanoparticles and the antigen/adjuvant as well as the factors controlling the interaction between nanoparticles and the receptors on antigen presenting cells. Besides, the role of nanoparticles in targeting/activating immune cells and modulating the immunosuppressive tumor microenvironment has also been discussed extensively. Finally, we have summarized some theranostic applications of the immunomodulatory nanomaterials in treating cancers based on the earlier published reports.
