Stimuli-Sheddable Nanomedicine Overcoming Pathophysiological Barriers for Potentiating Immunotherapy of Cancer.

Immunotherapy displays potent potential for clinical cancer management by activating the protective immune response; however, the microenvironment of the immunosuppressive tumor restricts the efficiency of immunotherapies. Along with the complex pathophysiological barrier of the solid tumors, successful immunotherapeutic delivery remains a formidable challenge for conventional nanomedicine. Stimuli-sheddable nano vectors may facilitate the delivery of cargoes to tumors with minimal premature cargo leakage in blood circulation while enhancing the tumor penetration of nanomedicines by deshielding the polyethylene glycol (PEG) corona upon endogenous activity such as acidity, enzymes and glutathione, or external stimuli, such as laser irradiation. Throughout this study, researchers overviewed the recent advances of nanomedicine-based cancer immunotherapy using the stimuli-responsive deshielding nano vectors, which allowed researchers to integrate multiple therapeutic regimens for inducing immunogenic cell death. This aided in blocking the immune checkpoints, repolarizing the macrophages, and regulating the kynurenine metabolism. Furthermore, researchers discussed the critical issues in the development of stimuli-sheddable nanoimmunodulators, primarily aimed at speeding up their clinical translation. Finally, researchers provided novel perspectives for improving cancer management with the stimuli-sheddable nanomedicine.