THERAPEUTIC USE OF CuO-BIOPOLYMER BASED NANOPARTICLES FOR TARGETED DRUG DELIVERY TOWARDS BREAST CANCER

Abstract

Cancer remains a significant threat to human health and a critical challenge in modern clinical settings. Despite laudable strides taken towards ameliorating the lives of cancer patients, the eradication of this debilitating disease demands a thorough exploration of cutting-edge materials. Fortunately, nanomedicine has emerged as a promising avenue for innovative cancer therapeutics by enhancing current systems through the discovery of intelligent targeted nanoparticles (NPs) that can deliver chemotherapeutic agents at a sustained rate directly to cancerous cells, potentially leading to superior efficacy and reduced toxicity for treating primary as well as advanced metastatic tumors. Moreover, amalgamation of biodegradable polymers with metal oxide nanoparticles can help circumvent chemoresistance and enhance the production of reactive oxygen species (ROS), ultimately bolstering targeted therapy approach. Thus, the current thesis is an endeavor to develop copper oxide-biopolymer based nanoparticles for efficacious targeted drug delivery in the breast cancer treatment, with the goal of addressing multifunctionality in novel nanomedicines. First part of the study focusses on the synthesis of CuO nanoparticles via precipitation technique that is loaded with anticancer drug paclitaxel (PTX), and enclosed in a PHBV matrix to enhance its effectiveness. The process of PEGylation is then employed to enhance their water solubility, followed by functionalization with folic acid to enable targeted delivery. Several physicochemical characterization techniques were utilized to validate the formation of CuO-PTX@PHBV-PEG-FA nanoparticles. These NPs were efficiently taken up by cells and elicited synergistic antiproliferative effects in human breast adenocarcinoma (MCF-7) cells at lower concentrations. Hemolysis study ensure the blood biocompatibility and safety of the developed nanosystem for intravenous drug delivery. Moreover, cell-based studies confirm the induction of apoptosis by CuO-PTX@PHBV-PEG-FA NPs morphologically through enhanced ROS production and nuclear fragmentation.