Chondroitin Sulphate-based hydrogels loaded with folic acid-functionalized nanoparticles to target colorectal cancer

Abstract

Colorectal cancer (CRC) patients continue to be a major cause of cancer-associated morbidity and mortality worldwide. Traditional chemotherapies are least effective due to low bioavailability of drugs at tumor locations, off-target systemic toxicity, and poor oral delivery of hydrophobic drugs. This research describes the first smart nanoparticles-loaded hydrogel system (SNHS) capable of targeted, sustained oral delivery of chemotherapeutics. The system combines folic acid-conjugated nanoparticles for targeted delivery to tumors. Along with pH-sensitive polymeric hydrogels capable of controlled release in the gastrointestinal tract. Comprehensive physicochemical analysis, such as X-ray diffraction, FTIR, SEM, thermal analysis, and dynamic light scattering, assured nanoparticles' stability and ligand conjugation. In-vitro studies proved effective drug loading, entrapment, and sustained release profile up to 70 h in simulated gastric and intestinal fluids. Cellular uptake and cytotoxicity tests on folate receptor-positive (HT-29, HeLa) and FR-negative (A-549) cell lines support receptor-mediated nanoparticle internalization and selective toxicity. The MTT assay on non-cancerous CCD841 cells showed the safety of the developed formulations for non-cancerous healthy cells. The in vivo assessment in the Ht-29 xenograft model of colorectal cancer identified significant inhibition of tumor growth and enhanced survival, tracked by IVIS imaging. The synergistic benefits of targeted nanoparticle delivery and hydrogel-mediated sustained release highlight the potential of SNHS as a viable oral therapeutic platform for CRC. This strategy overcomes major limitations of existing chemotherapy by increasing drug bioavailability, specificity, and patient compliance.