CISPLATIN-LOADED ZINC–POLYETHYLENE GLYCOL NANOPARTICLES EXHIBIT ENHANCED ANTICANCER EFFICACY AND REDUCED SYSTEMIC TOXICITY IN A MURINE MELANOMA MODEL

Abstract

Background: Cisplatin remains a cornerstone chemotherapeutic agent; however, its clinical utility is constrained by dose-limiting nephrotoxicity, myelosuppression, and the emergence of drug resistance. Zinc–polyethylene glycol (Zn-PEG) nanoparticles offer a promising platform to overcome these limitations through enhanced tumor accumulation via the enhanced permeability and retention (EPR) effect, surface PEGylation-mediated immune evasion, and intrinsic zinc-mediated pro-apoptotic activity.

Objective: This study aimed to synthesize, physicochemically characterize, and evaluate the in vivo anticancer efficacy and systemic safety of cisplatin-loaded Zn-PEG nanoparticles (CIS/Zn-PEG NPs) in a syngeneic B16F10 murine melanoma model.

Methods: Nanoparticles were synthesized using a co-precipitation method by combining zinc acetate, PEG-2000, and sodium hydroxide under continuous stirring conditions. Subsequently, cisplatin was added gradually into the Zn-PEG nanoparticle suspension to obtain cisplatin-loaded nanoparticles. The synthesized nanoparticles were characterized through dynamic light scattering (DLS), zeta potential analysis, Fourier-transform infrared spectroscopy (FTIR), and UV–Visible spectroscopy to evaluate their physicochemical and structural properties. For the in vivo investigation, Sprague–Dawley rats bearing melanoma tumors induced using the B16F10 cell line were utilized as the experimental model. Animals were randomly allocated into four experimental groups, including a vehicle control group, a disease control group, a free cisplatin-treated group, and a cisplatin-loaded nanoparticle-treated group. Tumor progression and body weight were monitored throughout the 22-day experimental period. In addition, hematological and biochemical analyses were performed to evaluate hepatic and renal function, while the expression levels of important biomarkers, including vascular endothelial growth factor (VEGF) and p53, were also assessed.

Results: The nanoparticles emerged with an approximate size of 150 nm, a zeta potential of -18.4 mV, and a cisplatin loading efficiency of 78.3% all solid indicators of a well-formed formulation that is stable.

The animals with the nanoparticle treatment had decrease in tumor size than those receiving cisplatin (p < 0.001), and therefore had a longer survival. Notably, the stress markers creatinine, urea, ALT, and AST of the kidney and liver were significantly reduced in the nanoparticle group, which indicates that the formulation was significantly milder to the body. To top this, the VEGF levels decreased significantly, and the p53 increased which informs us that the treatment was actively driving the cancer cells to self-destruction.

Conclusion: CIS/Zn-PEG nanoparticles demonstrated superior antitumor efficacy and reduced systemic toxicity compared with free cisplatin. These findings suggest that Zn-PEG-based nanocarriers may represent a promising strategy for improving melanoma treatment through enhanced therapeutic efficacy and safety.