Chitosan-Coated Silver Nanourchins for Imatinib Mesylate Delivery: Biophysical Characterization, In-Silico Profiling, and Anti-Colon Cancer Efficacy.

Abstract

This study investigates the synthesis and characterization of silver nanourchins coated with chitosan (IMT-CS-AgNUs) as a novel platform for the delivery of imatinib mesylate (IMT) for the treatment of colon cancer. In-silico analysis discovered 10 key metabolites for IMT, which have associated respiratory and neurotoxic risks. Molecular docking studies showed the high affinity binding of IMT to critical proteins, including BCL2 (-6.637 kcal/mol), Caspase-6, and EGFR, which proved its potential therapeutic value. IMT-CS-AgNUs were prepared by ionic gelation, and the nanoparticles had a size of 192.98 nm, with an entrapment efficiency of 85.7%. The FTIR and XRD structural characterization confirmed that the nanocarriers were stable and amorphous in nature. In vitro studies of HCT116 cells showed significantly increased cytotoxicity with an IC50 of 0.4 μg/mL; apoptosis by 42.5% and ROS generation by 47.8% when compared to only IMT. The release of drugs from the nanoparticles was sustained over 85% over 60 h, selectively inhibited pathogenic bacteria without harming beneficial microbes, and showed antiangiogenic activity, which is validated through the HET-CAM assay. Gene expression analyses showed that there was marked downregulation of BCL2 and upregulation of apoptotic genes. Pharmacokinetic studies in Wistar rats showed improved bioavailability by 1.8, which allows targeted drug concentrations in the colon with lessened systemic toxicity. Thus, the development of IMT-CS-AgNUs represents a potent approach for targeted colon therapy against cancer, providing therapeutic efficacy, controlled drug release, and added safety.