Quercetin-loaded zinc oxide nanoparticles encapsulated in chitosan-alginate: a synergistic approach to cancer and bacterial therapy.

Zinc oxide (ZnO) nanoparticles (NPs) exhibit promising antibacterial and anticancer properties. However, their cytotoxicity toward normal cells limits their therapeutic potential. To overcome this challenge, ZnO nanoparticles were loaded with quercetin (ZnO@Qc) and encapsulated within a chitosan-alginate composite, aiming to enhance their efficacy while reducing side effects. ZnO NPs were synthesized, characterized, and loaded with quercetin before being coated with a chitosan-alginate biopolymer. The antimicrobial activity was assessed through MIC and MBC assays against Gram-positive and Gram-negative bacteria. The cytotoxic effects were evaluated in HUVEC (normal) cells, and anticancer properties were analyzed in MCF-7 and MDA-MB-231 breast cancer cells using MTT, apoptosis (flow cytometry), scratch, and colony formation assays. Drug release kinetics were also studied at different pH levels. The chitosan-alginate-coated ZnO@Qc nanocomposite showed enhanced antibacterial activity, with lower MIC and MBC values compared to uncoated ZnO@Qc. The nanocomposite significantly reduced cytotoxicity toward normal HUVEC cells while maintaining strong anticancer effects, including dose-dependent inhibition of cell viability, apoptosis induction, and reduction in colony formation and cell migration. Gene expression analysis confirmed the upregulation of apoptotic markers (CASP3, CASP8, CASP9). Drug release studies demonstrated a controlled and pH-sensitive release of quercetin, favoring targeted delivery in the tumor microenvironment. The chitosan-alginate-coated ZnO@Qc system enhances antibacterial and anticancer efficacy while mitigating toxicity in normal cells. This multifunctional nanostructure holds promise for targeted breast cancer therapy and antimicrobial applications.