Precise Molecular Engineering of Multi‐Suborganelle Targeted NIR Type‑I AIE Photosensitizer and Design of Cell Membrane‐Anchored Anti‐Tumor Pyroptosis Vaccine

Abstract Photodynamically induced cell immunogenic death has emerged as an effective antitumor strategy because of its capacity to stimulate anti‐tumor immunity for eliminating primary tumors and metastases. Considering that the short‐lived reactive oxygen species (ROS) and the anoxic tumor microenvironment restrict the efficacy of conventional photodynamic therapy (PDT), a molecular framework of near‐infrared (NIR) type I aggregation‐induced emission (AIE) photosensitivities with tunable sub‐organelles (including cell membranes, mitochondria, lipid drops, lysosomes, and endoplasmic reticulum) targeting type I ROS in precisely regulated subcellular locations are designed. Subsequent studies have discovered that under 660 nm laser irradiation, the cell membrane‐targeted TCF‐Mem can effectively induce pyroptosis of cancer cells, fully enhancing anti‐tumor immunity in vivo in a preventive tumor vaccine model. Additionally, in vivo anti‐tumor type I PDT can eradicate the primary tumor and, more importantly, inhibit the growth of distant tumors through in vitro actions, thereby obtaining specific anti‐tumor immunity. This study provides a novel framework for the rational design of photosensitive sub‐organelles targeting NIR type I AIE and offers a new perspective for innovative PDT‐based tumor therapy and immune enhancement strategies.