Development and characterization of engineered gingerol loaded chitosan nanoparticles for targeting colon cancer, bacterial infection, and oxidative stress mitigation.

This study presents the development of a multifunctional nanotherapeutic platform based on gingerol (GN) loaded chitosan nanoparticles (GN@CsNPs), designed to simultaneously target colorectal cancer, combat enteric bacterial infections, and alleviate oxidative stress. The nanoformulation system demonstrated a high sustained release profile, releasing 60 % of GN within 8 h and achieving 98.5 % cumulative release under acidic conditions (pH 4.2) over 72 h, supporting targeted colonic delivery. Cytotoxicity assays against HCT-116 colon cancer cells revealed strong dose-dependent effects, with an IC50 of 73.2 μg/mL and up to 93.4 % inhibition of cell viability at 250 μg/mL. Antibacterial evaluations confirmed broad-spectrum efficacy, with inhibition zones of 19 ± 0.36 mm (E. coli) and 21 ± 0.82 mm (Salmonella enterica), MIC values ranging from 150 to 300 μg/mL, and MBC values up to 350 μg/mL. Time-kill studies demonstrated complete bacterial eradication within 15-30 min at 2 × MIC. Antioxidant analysis revealed robust free radical scavenging (83.0 % at 1000 μg/mL), with an IC50 of 30.9 μg/mL, significantly outperforming unloaded CsNPs. Molecular docking studies supported the dual functionality of GN, showing high binding affinity to both mTOR (-6.1 kcal/mol) and gtfB (-6.1 kcal/mol), implicating its roles in anticancer and antimicrobial mechanisms. In conclusion, the results position GN@CsNPs as a promising bio-based nanotherapeutic for integrated management of colorectal cancer, microbial infections, and oxidative stress-related conditions.