Chemiluminescence‐Powered Immunotherapy for Deep Tumors: Promoting PD‐L1 Degradation and Igniting Pyroptosis Through Subcellular Trafficking and Targeting

Organelle-targeted therapy represents a promising strategy for cancer therapy and immune activation. Here, we present a novel Chemiluminescence-Powered Immunotherapy (CPIT) platform designed to induce immunogenic pyroptosis and promote PD-L1 degradation by exploiting two key subcellular organelles-lysosomes and the endoplasmic reticulum (ER). CPIT utilizes a PD-L1-targeted delivery vehicle (up to 10.8 %ID/g) to facilitate PD-L1 degradation within lysosomes (>55% efficiency) and concurrently delivers a dual-locked chemiluminescence-resonance energy transfer (CRET) system to the ER for localized pyroptosis. The dual-locking mechanism ensures tumor-selective and ER-confined activation, maximizing oxidative damage…

• NN
  National Natural Science Foundation of China

  Awards: 52373144, 52122305
• FR
  Fundamental Research Funds for the Central Universities

  Award: 63253262