Biocompatible Chitosan/Starch/Graphene Quantum Dots/Titanium Dioxide Nanocomposite: A Stimuli-Responsive, Porous Nanocarrier for Prolonged Quercetin Delivery in Lung Cancer Treatment

Quercetin (QC), a naturally occurring antioxidant, has demonstrated potential in the prophylaxis and therapy of various cancer types. Despite its biocompatibility and minimal side effects, its therapeutic efficacy is limited by its low physicochemical stability, poor solubility, and suboptimal bioavailability. This study proposes a novel approach to address these limitations and augment the pharmacokinetics of QC, specifically its half-life and overall delivery efficacy. The W/O/W was employed to load QC into a chitosan (CS)/Starch/graphene quantum dots (GQDs)/titanium dioxide (TiO 2 ) nanocomposite, serving as a stimuli-responsive nanocarrier. The CS/Starch hydrogel was synthesized via a physical crosslinking process to optimize biocompatibility. Subsequently, GQDs and TiO 2 were incorporated to induce porosity within the system. The porosity was examined pre and post QC integration using Brunauer–Emmett–Teller (BET) analysis. The successful incorporation of QC and the crystalline properties of the resultant drug-loaded nanocomposite, CS/Starch/GQDs/TiO 2 @QC, were confirmed through Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses, respectively. Morphological evaluations were conducted using zeta potential, dynamic light scattering (DLS), and field emission scanning electron microscopy (FESEM) to ascertain the size, stability, and homogeneity of the nanoparticles. The encapsulation and loading efficiencies, along with release kinetics, were assessed under varying pH (5.4 and 7.4) and temperature (37 °C and 42 °C) conditions. The results indicated Fickian diffusion as the primary QC release mechanism, exhibiting stimuli-responsive behavior. The cytotoxicity of the CS/Starch/GQDs/TiO 2 @QC nanocomposite was evaluated against the A549 cell line using the MTT assay, demonstrating enhanced cytotoxicity compared to QC alone. In light of these findings, the study advocates for the use of the CS/Starch/GQDs/TiO 2 nanocomposite as a biocompatible, porous, and stimuli-responsive nanocarrier for the sustainable delivery of QC in lung cancer therapy.