From chemistry to targeted cancer therapy: potent benzimidazole-1,2,3-triazole hybrid-loaded nanogels against breast and colorectal malignancies

Abstract

The therapeutic limitations of conventional anticancer agents, particularly in treating mucosal and epithelial malignancies such as breast and colorectal cancers, necessitate the development of advanced drug delivery systems. This study explores the integration of benzimidazole-1,2,3-triazole hybrids into chitosan/polyvinyl pyrrolidone nanogels to enhance pharmacological performance and target specificity. Comprehensive physicochemical characterization confirmed successful encapsulation and favorable nanogel properties, including controlled particle size, stability, and morphology. Among the tested formulations, the 12ng nanogel demonstrated superior cytotoxicity against the epithelial cancer cells, MDA-MB-231 (IC₅₀ = 3.13 ± 0.22) and Caco-2 (IC₅₀ = 3.64 ± 0.25) µM, surpassing the reference drug staurosporin. Enzymatic assays revealed potent inhibition of topoisomerase I and II, as well as tubulin polymerization. Flow cytometry and apoptosis analysis confirmed G0/G1 cell cycle arrest and late-stage apoptosis induction. Molecular docking studies supported the strong binding affinity (−9.50 kcal mol⁻¹) of 12ng to topoisomerase I, validating its' multitarget mechanism. These findings underscore the potential of nanogel-delivered benzimidazole-1,2,3-triazole hybrids as promising candidates for targeted cancer therapy.