Biodegradable Folate-Mediated Chitosan-CQD Nanocarriers for Targeted and Stimuli-Responsive Cisplatin Delivery in Melanoma

Abstract

Polymeric nanoparticles provide an effective platform for drug delivery owing to their biocompatibility, biodegradability, and high drug-loading capacity. Chitosan, a natural cationic biopolymer, is particularly attractive because of its mucoadhesive nature, pH responsiveness, and structural stability. In this work, a cisplatin-loaded chitosan-based nanocarrier was developed by integrating green-synthesized fluorescent carbon quantum dots (CQDs) and surface functionalizing them with folic acid (FA) to enhance melanoma-targeted theranostic performance. Physicochemical characterization using UV–Vis spectroscopy, dynamic light scattering, and FTIR confirmed successful nanoparticle formation, surface functionalization, and colloidal stability, with a high cisplatin encapsulation efficiency (>70%). Hemocompatibility studies revealed negligible hemolysis, indicating excellent blood compatibility. The FA-conjugated cisplatin-loaded chitosan–CQD nanoconjugates (FA-CisCCNPs) exhibited significantly enhanced cytotoxicity against B16 melanoma cells, with markedly lower IC₅₀ values compared to free cisplatin and non-drug-loaded FA–CCNPs. Fluorescence-based cellular internalization studies demonstrated efficient uptake of the nanoconjugates by melanoma cells, consistent with folate receptor-mediated endocytosis. In vivo studies in melanoma-bearing mice showed substantial tumor regression (approximately 70%), along with reduced systemic toxicity in vital organs and favorable modulation of oxidative stress biomarkers. Histopathological and immunohistochemical analyses further associated tumor suppression with p53 overexpression and Bcl-2 downregulation, supporting the potential of FA-CisCCNPs as a green-synthesized, biodegradable, and stimuli-responsive nanoplatform for targeted melanoma therapy.