Endogenous stimuli-activatable nanomedicine for immune theranostics for cancer

Cancer immunotherapy has witnessed significant advances in the past decade, however challenges associated with immune-related adverse effects and immunosuppressive tumor microenvironment, have hindered their clinical application. Stimuli-activatable nanomedicines hold great potential for improving the efficiency of cancer immunotherapy and minimizing the side effects via tumor-specific accumulation, controllable drug release profile, and combinational therapy by integrating multiple therapeutic regimens. In this review, the recent advances of stimuli-activatable nanomedicines for cancer immunotherapy are first described, with particular focus on endogenous stimuli including pH, glutathione, reactive oxygen species, and excessive enzymes within the tumor microenvironment. Then, the endogenous stimuliactivatable nanomedicines that target tumor cells, immune cells, or periphery immune systems for eliciting sustained systemic immune activation and modulating the immunosuppressive tumor microenvironment, are described. Next, the general mechanisms underlying nanomedicine-based immunotherapy by eliciting anti-tumor immune responses and overcoming immunologic tolerance are described. Further, the emerging application of bioimaging techniques for monitoring immune response and evaluating therapy performance is described. Finally, the authors' perspectives are provided for the clinical translation of nanomedicine-based cancer immunotherapy.