Cascade Amplification of Pyroptosis and Apoptosis for Cancer Therapy through a Black Phosphorous-Doped Thermosensitive Hydrogel

Cell pyroptosis has a reciprocal relationship with various cancer treatment modalities such as chemotherapy. However, the tumor microenvironment, characterized by hypoxia, substantially restricts development and application of therapies that integrate cell pyroptosis. Therefore, cascade amplification oxidative stress interfering redox homeostasis in tumors may be promising approach. In this study, black phosphorus (BP) nanosheets glutathione peroxidase 4 inhibitor (RSL3) were coloaded into thermosensitive PDLLA-PEG-PDLLA (PLEL) hydrogel (RSL3/BP@PLEL). Owing to photothermal property BP nanosheets, RSL3/BP@PLEL trigger release loaded drugs more controllable on-demand manner. Investigation antitumor effect mouse liver model demonstrated local injection formulation combination near infrared laser irradiation could efficiently suppress growth balance tumors. Mechanistic study indicated combined therapy depletion based on induced through both caspase-1/GSDMD caspase-3/GSDME pathways, thereby triggering repolarization tumor-associated macrophages from M2 M1. Overall, we developed biocompatible biodegradable for treatment, providing new platform enhancing efficacy amplifying apoptosis.