pH-Responsive Chitosan-Based Nanoparticles for Targeted Drug Delivery and Immunomodulation in Cancer Therapy

This research aimed to develop and assess pH-responsive chitosan nanoparticles for the targeted delivery of doxorubicin in cancer treatment. Ionic gelation was used to make nanoparticles, which were then tested for size, shape, zeta potential, drug loading, and release behaviour. The optimised formulation exhibited a spherical morphology with an average diameter of approximately 150 nm, a high positive surface charge, and an entrapment efficiency surpassing 80%. Under acidic conditions, drug release was much faster than at physiological pH, which showed that the drug was pH-responsive. In vitro assays indicated that DOX-loaded nanoparticles improved cellular uptake, stimulated increased apoptosis, and exhibited heightened cytotoxicity against MCF-7 and HeLa cancer cells, while displaying diminished toxicity in non-malignant HEK-293 cells. Furthermore, the nanoparticles stimulated macrophages, elevated the secretion of TNF-α, IL-6, and nitric oxide, and facilitated M1 polarisation. These results indicate that chitosan-based smart nanoparticles may be an effective dual-purpose system for chemotherapy and immunomodulation in cancer therapy.