A Self-Adaptive Pyroptosis Inducer: Optimizing the Catalytic Microenvironment of Nanozymes by Membrane-Adhered Microbe Enables Potent Cancer Immunotherapy.

Abstract

Pyroptosis has garnered increasing attention in cancer immunotherapy. Moreover, increasing plasma membrane damage by reactive oxygen species (ROS) is considered an effective strategy for promoting pyroptosis. However, the current tactics for enhancing membrane rupture in pyroptosis are limited by the inherent drawbacks of ROS and the immunosuppressive tumor microenvironment. Herein, a self-adaptive pyroptosis inducer (LPZ) is designed by integrating Lactobacillus rhamnosus GG (LGG) and an enzyme-like metal-organic framework to achieve potent pyroptosis immunotherapy. LPZ can adhere to cancer cell membranes through the interaction between the pili of LGG and the mucin of cancer cells. In particular, the adaptive formula can gradually enhance the ability of nanozymes to produce ROS by creating an acidic microenvironment through anaerobic respiration. These results verify that LPZ could generate high levels of ROS both on the membrane and within cancer cells, leading to pyroptotic cell death and strong antitumor immunity. Meanwhile, LGG are eventually killed by ROS in this process to halt their respiration and prevent potential biosafety concerns. Overall, this work provides new inspiration for the design of self-adaptive nanocatalytic drugs for cancer immunotherapy.