Quercetin and resveratrol loaded polymeric nanoparticle for colorectal cancer as pH sensitive approach

Colorectal cancer (CRC) continues to pose a significant global health challenge, requiring sophisticated tailored therapy with less adverse effects. Resveratrol and quercetin, two bioactive flavonoids, exhibit significant anticancer effects but are hindered by low bioavailability and quick degradation. This research details the development of pH-sensitive polymeric nanoparticles (NPs) co-encapsulating resveratrol and quercetin, utilizing poly (lactic-co-glycolic acid) (PLGA) and Eudragit S100 for targeted colorectal cancer therapy. The optimized QRNPs exhibited particle size of 174–177 nm, a zeta potential around −22 to −24 mV, and encapsulation efficiency exceeding 80%. In vitro, drug release studies demonstrated minimal release at pH 7.4 but increased release at acidic pH (5.5), which is consistent with tumor microenvironments. Cytotoxicity assays in Caco-2 colon cancer cells revealed significantly enhanced cytotoxicity of QRNPs compared to free drugs, with CC₅₀ values of 48.84 µg/mL (24 h) and 32.75 µg/mL (48 h). FTIR confirmed drug–polymer compatibility, and HR-TEM analysis showed uniform spherical morphology. Stability tests in simulated GI fluids validated formulation robustness. Furthermore, fluorescence imaging and Annexin V-FITC assays confirmed augmented cellular uptake and elevated apoptosis. Mechanistic investigations revealed a downregulation of the anti-apoptotic protein Bcl-2 and an overexpression of the pro-apoptotic proteins Bax and caspase-3. The results underscore the promise of resveratrol-quercetin co-loaded pH-sensitive polymeric nanoparticles as a viable method for targeted colorectal cancer therapy.