The　development　of　a　simple　drug　formulation　capable　of　achieving　both　activatable　type　I　photoreaction　and　tumor-responsive　release　of　immunomodulator　is　crucial　for　advancing　photodynamic　immunotherapy　(PDIT).　Herein,　we　present　a　nanostructured　photosensitizer　(NP5)　that　is　activated　by　the　acidic　tumor　microenvironment　to　produce　type　I　reactive　oxygen　species　(ROS)　under　light　irradiation　and　release　the　immunomodulator　demethylcantharidin　(DMC)　for　PDIT.　The　NP5　is　formed　by　self-assembly　of　a　versatile　phthalocyanine　molecule　which　is　composed　of　DMC　and　phthalocyanine　linked　via　a　pH-responsive　amide　bond.　NP5　produces　minimal　ROS　under　light　irradiation　at　the　condition　of　pH　7.4.　However,　NP5　can　release　DMC　at　the　condition　of　pH　6.5　and　concurrently　trigger　type　I　photoreactions.　The　results　of　in　vivo　experiments　indicate　that　NP5-mediated　PDIT　induce　the　increase　of　cytotoxic　T　lymphocytes　and　decrease　of　regulatory　T　lymphocytes,　which　can　effectively　inhibit　the　bilateral　tumor　growth.　This　work　is　anticipated　to　serve　as　a　reference　for　the　development　of　innovative　agents　for　precise　PDIT　of　hypoxic　tumors.　©　2024　Elsevier　B.V.