Design, mechanism and translational perspectives of redox responsive nanogels for tumor microenvironment triggered drug delivery

Malignant tissues are distinguished from healthy tissues by the tumor microenvironment’s strong redox heterogeneity, which is typified by increased intracellular glutathione levels and dysregulated reactive oxygen species. This biochemical imbalance offers a logical catalyst for the creation of redox-responsive nanogels that can release medications intracellularly and at specific sites. Nanogels have become a versatile platform for the delivery of cancer drugs because of their hydrated three-dimensional polymeric networks, high loading capacity, and tunable degradability. These systems undergo rapid degradation in the reductive or oxidative environments of tumor cells while remaining stable during systemic circulation, thanks to the incorporation of redox-labile linkages like disulfide, diselenide, or tellurium-based bonds into their crosslinked architectures. The redox characteristics of the tumor microenvironment and their demonstrations for nanogel systems are critically suggested in this review, with focus on polymer choice, crosslinking chemistry, fabrication techniques, and release mechanisms. In addition to new translational initiatives and clinical considerations, recent developments in redox-triggered chemotherapy, gene delivery, immunomodulation, and theranostic applications are covered. The need for logical design strategies that connect laboratory innovation and clinical applicability in redox-responsive cancer nanomedicine is finally emphasized by highlighting current issues with scalability, biological complexity, and regulatory translation. Redox-responsive nanogels utilize elevated intracellular glutathione levels for precise, site-specific drug release. Incorporation of redox-labile linkages ensures rapid degradation under tumor-specific conditions. Nanogels offer tuneable physicochemical properties, high drug-loading capacity, and compatibility with active agents. These nanogels demonstrate efficacy in chemotherapy, gene delivery, immunotherapy, and phototherapy, enhancing treatment outcomes.