Strategic Design of Intelligent-Responsive Nanogel Carriers for Cancer Therapy

Owing to the distinctive constituents of tumor tissue from those healthy organs, nanomedicine strategies show significant potentials in smart drug delivery. Nowadays, stimuli-responsive nanogels are playing increasingly important roles in the application of cancer therapy because of their sensitivity to various internal or external physicochemical stimuli, which exhibit site-specific and markedly enhanced drug release. Besides, nanogels are promising as drug carriers because of their porous structures, good biocompatibility, large surface area, and excellent capability with drugs. Taking advantage of multiresponsiveness, recent years have witnessed the rapid evolution of stimulus-responsive nanogels from monoresponsive to multiresponsive systems; however, there lacks a comprehensive review summarizing these reports. In this Review, we discuss the properties, synthesis, and characterization of nanogels. Moreover, tumor microenvironment and corresponding designing strategies for stimuli-response nanogels, both exogenous (temperature, magnetic field, light) and endogenous (pH, biomolecular, redox, ROS, pressure, hypoxia) are summarized on the basis of the recent advances in multistimuli-responsive nanogel systems. Nanogel and two-dimensional material composites show excellent performance in the field of constructing multistimulus-responsive nanoparticles and precise intelligent drug release integrated system for multimodal cancer diagnosis and therapy. Finally, potential progresses and suggestions are provided for the further design of hybrid nanogels based on emerging two-dimensional materials.