Stimuli-responsive nanogels as intelligent nanocarriers for tumor microenvironment-triggered anticancer drug delivery

Stimuli-responsive nanogels have been utilized as perfect nanocarriers for anticancer drug delivery because of their on-demand, controlled, and site-specific drug-releasing chemistry. These HNP are cross-linked hydrophilic polymer nanoparticles with a high-water content, biocompatibility, and adjustable reactivity to chemical or physical stimuli (such as pH, temperature, and redox potential, which are among the most extensively studied triggers in cancer-targeted nanogel systems). Because of their structural flexibility, these nanocarriers can react intelligently and passively to the tumor microenvironment's high glutathione content, acid pH, and overexpressed enzymes, ensuring increased intracellular release and reduced systemic toxicity. Cross-linking strategies, top-down and bottom-up production processes, and core characterization methods concerning size, charge, morphology, and release kinetics are the main topics of this article. Anticancer medications like doxorubicin, paclitaxel, camptothecin, and docetaxel have been shown to be well accommodated in a variety of nanogels, including pH-responsive, thermo-responsive, redox-responsive, magnetic-based, and multi-responsive ones for increased bioavailability and anti-tumor activity. In addition, receptor-mediated endocytosis mediated by targeting ligands such as folic acid, hyaluronic acid, aptamers and monoclonal antibodies improves the cellular uptake and uptake in tumor of drug-loaded nanogels. Collectively, intelligence-triggered nanogels stated above possess outstanding benefits in combination therapy, controlled drug release, and theranostic application and so illustrate these as state-of-the-art intelligent delivery systems for tumor treatment. Future goals include optimizing biocompatibility, removing tumor penetration obstacles using techniques including surface charge modification, PEGylation, and enzyme-sensitive cross-linkers, and guaranteeing scalability and therapeutically transferable formulations.