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

Stimuli-responsive nanogels are being investigated as novel nanocarriers for the targeted delivery of anticancer drugs. These nanogels are cross-linked hydrophilic polymer nanoparticles that offer high-water content, biocompatibility, and adjustable reactivity to the stimuli present in the tumor microenvironment. pH, temperature, and redox potential are the most researched stimuli for cancer therapies. Because of structural flexibility, passive responses are feasible to elevated glutathione levels, an acidic microenvironment, and over-expressed enzymes in tumor sites. Such flexibility is advantageous for enhanced intracellular delivery of drugs while also reducing off-target toxicity. This research involves the study of various cross-linking methods as well as top-down and bottom-up techniques for the fabrication and characterization of nanogels

with respect to particle size, surface charge, morphology, and drug release kinetics. The various types of nanogels discussed are pH-responsive, thermo-responsive, redox-responsive, magnetically responsive, and multi-responsive systems which can improve the bioavailability and anti-tumor efficacy of drugs such as doxorubicin, paclitaxel, camptothecin, and docetaxel. Additionally, the use of targeting ligands such as folic acid, hyaluronic acid, aptamers, and monoclonal antibodies is discussed along with its contributions to receptor-mediated endocytosis, thereby increasing the cellular and tumor-specific uptake of drug-loaded nanogels.

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