De Novo Construction of Glutathione Activatable Photosensitizers Boosts Sequential Photoacoustic and Fluorescence Imaging and Precise Photodynamic Therapy

Ar) chemistry, led by 2,4-dinitrobenzenesulfonate group, realizes the switching of aPSs from off to on through the photo-induced electron transfer (PeT) effect. However, the ultra-sensitive reactivity to glutathione (GSH) greatly reduces the precision of diagnosis and PDT. Herein, we focused on the quenching efficiency and precise activation through structure-activity relationships to optimize the phthalocyanine-based aPSs (PcGx). The improved PcGx could distinguish GSH levels from cancer cells to normal cells. Moreover, cancer cell membrane targeting hyaluronic acid carrier is introduced to construct J aggregation-driven nanoplatform (PcGx@HP). This nanoplatform could not only stabilize and enhance the J aggregation, but also obtain the sequential photoacoustic and fluorescence imaging in vivo. Subsequent studies verifies that PcGx@HP could inhibit tumor growth without off-target toxicity in breast cancer xenograft model. This study provides a reliable method for the de novo construction and development of precise aPSs for sequential imaging and photodynamic therapy.