Abstract

Abstract In photodynamic therapy (PDT), the elevated glutathione (GSH) of cancer cells have two sides for treatment efficacy, activation pre‐drug by removing activity suppressor part (advantages) and consumption reactive oxygen species (ROS) to confer PDT resistance (disadvantages). Preparation all‐in‐one system by simple method to make best use of the advantages and bypass the disadvantages still were remains a technical challenge. Herein, we report a robust PDT nanoparticle with above function based on a self‐assembled pyridine modified Zinc phthalocyanine (ZnPc‐DTP). The activity suppressor and active part of ZnPc‐DTP were linked by disulfide bond. After targeting cancer cells, GSH can react with ZnPc‐DTP nanoparticles by cutting disulfide bond to release its active part (ZnPc‐SH) and oxidize GSH. In vitro and in vivo results indicated that ZnPc‐SH can effective suppress tumor growth under the low antioxidant tumor microenvironment (TME). Graphical abstract Figure. No Caption available. HighlightsHigh GSH level in cancer cell make its antioxidant capacity to consume ROS in PDT.A new self‐assembled Zinc phthalocyanine nanoparticle is design and synthesized.The PDT activity of the particle could be activated by GSH.The particle can destroy GSH to reduce antioxidant capacity and improve PDT effect.