Preparation and evaluation of multi-functional Nimbolide-loaded PLGA/chitosan nanoparticles as a potential therapy for renal cell carcinoma through activation of intrinsic apoptotic pathway.

Renal cell carcinoma (RCC), a malignant tumor of the heterogeneous renal tubule epithelium, is the second most common urinary system malignancy after bladder cancer. Global RCC prevalence is rising, according to epidemiological studies. The treatment for localized renal cell carcinoma is surgical removal, however patient-specific factors like health and postoperative chronic kidney disease must be considered. Anticancer drugs have been studied to improve preoperative outcomes and expand treatment options. Due to drug resistance, standard chemotherapeutic treatments are often ineffective in RCC. Nanocarrier-based drug delivery systems can increase targeted anticancer medication administration while lowering systemic toxicity. This study developed, characterized, and evaluated a Nimbolide-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticle system (NIM-CS-PLGA NPs) for passive targeting of RCC4 renal cancer cells. MTT experiments with NIM-CS-PLGA nanoparticles had much higher cytotoxic activity against RCC4 cells than free Nimbolide.Single-emulsion solvent evaporation was used to synthesize nanoparticles, which were physicochemical characterized using SEM, FTIR, and DLS for particle size and zeta potential assessment. Due to its positive surface charge and mucoadhesive properties, the chitosan coating increased nanoparticle uptake by contacting negatively charged cellular membranes. At the pH level 5.5 (cancer micro environment pH) the nimbolide release found to be 65 %. Apoptosis, indicated by chromatin condensation, nuclear fragmentation, and membrane permeabilization, was confirmed by nuclear staining with DAPI, Hoechst 33342, and Propidium iodide analysis. Further, the cell cycle analysis confirms that treated cell groups are showing G2/M phase arrest. The NIM-CS-PLGA nanoparticle formulation effectively induces apoptosis in RCC4 cells in in vitro condition. The in vivo findings demonstrate that NIM-CS-PLGA nanoparticles (NPs) effectively attenuate Fe-NTA-induced oxidative stress, as evidenced by decreased lipid peroxidation and increased levels of both enzymatic and non-enzymatic antioxidants. Furthermore, the formulation exhibits significant antitumor-promoting potential by mitigating Fe-NTA-induced toxicity and carcinogenesis. Nimbolide-loaded chitosan-coated PLGA nanoparticle technology improves renal cell cancer targeted therapy by increasing drug absorption, drug release, and pro-apoptotic activity induction.