The pH-controlled release properties of chitosan–gold nanoparticles encapsulated nobiletin to induce apoptosis through PI3K/AKT/mTOR signalling pathway on gastric cancer cell lines

Gastric cancer (GC) remains a major health concern with limited effective therapies. Nanotechnology-based drug delivery systems offer targeted and efficient treatment strategies. This study aimed to develop chitosan-coated gold nanoparticles loaded with Nobiletin (Ch-AuNPs-NB) and evaluate their anticancer potential by targeting the PI3K/AKT/mTOR signaling pathway in GC. <b>Materials and Methods</b> Ch-AuNPs were synthesized by NaBH₄ reduction and loaded with Nobiletin using nanoprecipitation. Characterization was done using UV-Vis, FTIR, XRD, DLS, and TEM. Drug loading, encapsulation efficiency, and pH-responsive release were assessed. Ch-AuNPs-NB (∼120 nm, PDI 0.247, +51 mV) showed enhanced drug loading (15%) and encapsulation efficiency (90.4%) at higher NB concentrations. The formulation demonstrated pH-responsive release over 72 hours and stability for 60 days. Ch-AuNPs-NB inhibited the PI3K/AKT/mTOR pathway, induced apoptosis, and arrested the cell cycle in AGS cells, highlighting its potential as a targeted GC therapy.