pH-Responsive Gold Nanoparticle/PVP Nanoconjugate for Targeted Delivery and Enhanced Anticancer Activity of Withaferin A

The development of advanced high-capacity nanoparticle-based drug loading, precise targeting, low toxicity, and excellent biocompatibility is critical for improving cancer therapeutics. Withaferin A, a natural steroidal lactone derived from Physalis minima, exhibits potential biological activity and holds promise as a therapeutic agent. In this study, a novel nanoconjugate (NC) was developed using gold nanoparticles (AuNPs) functionalized with polyvinylpyrrolidone (PVP), Withaferin A drug, and folic acid for targeted drug delivery in cancer treatment. The AuNPs–PVP–Withaferin A–FA nanoconjugate was synthesized through a layer-by-layer assembly process and was confirmed using UV–visible and FTIR spectroscopy. The hydrodynamic radius, surface charge, and morphology of the NC were characterized using dynamic light scattering (DLS), zeta potential analysis, and electron microscopy, respectively. The nanoformulation demonstrated a pH-responsive drug release, with 92% of Withaferin A released at pH 5, mimicking the tumor microenvironment. In vitro cytotoxicity studies conducted on MCF-7 cells using MTT assays, dual dye staining, and protein expression analysis revealed that the nanoconjugate effectively induced apoptosis in cancer cells. These outcomes emphasize the prospect AuNPs–PVP–Withaferin A–FA nanoconjugate as a targeted and efficient Withaferin A delivery system for cancer therapy, leveraging the inherent anticancer properties of Withaferin A.