Endogenous/exogenous stimulies inspired polyprodrug nano-inducer switches pyroptosis path for promoting antitumor immunity

Pyroptosis-based nanomedicine shows great potential to unchoke the bottlenecks of cancer immunotherapy, but hindered by precise and specific regulation of pyroptosis in tumor cells. Herein, we report an endogenous/exogenous stimulus-activatable unimolecular polyprodrug as nano-inducer (denoted as CCNP) to precisely regulate the process of gasdermin E (GSDME)-medicated tumor pyroptosis. This nano-inducer is specifically switched by noninvasive laser radiation and tumor microenvironment reactive oxygen species (ROS) and glutathione (GSH), and activates caspase-3, thus triggering GSDME-mediated pyroptosis. This three-pronged induced model of pyroptosis can fully play the therapeutic potency of combined chemotherapy and photodynamic therapy exported by nano-inducer, suggests a new perspective on how to multi-stimulus-responsive nanomedicine induces and precisely regulates the tumor cell pyroptosis for assisting immune checkpoint blockade therapy.