Three positive charge nonapoptotic-induced photosensitizer with excellent water solubility for tumor therapy

Photodynamic therapy (PDT) has emerged as a significant cancer therapy option. Currently, cation-based organic small molecule aggregation-induced emission (AIE) photosensitizers (PSs) attract the wide attention of many scientists, due to improved reactive oxygen species (ROS) production after cationization. However, such PSs tend to localize only the mitochondria, limiting the death way of tumor cells (usually apoptosis) during PDT process, which may affect the therapeutic effect under some circumstances. Herein, we designed a novel water-soluble three positive charge PS, TPAN-18F, which could be distributed uniformly in cell cytoplasm and had distribution in different sub-organelles (mitochondria, endoplasmic reticulum, lysosome). The experimental results showed that TPAN-18F-based PDT process can not only disrupt mitochondrial functions (reducing ATP production and destroying mitochondrial membrane potential), but also elevate the intracellular lipid peroxides (LPOs) level, which evoke the non-apoptotic death manner of tumor cells. Further, in vivo studies showed that TPAN-18F-based PDT could effectively inhibit tumor growth. Accordingly, we believe that the construction of TPAN-18F is suggestive for tumor non-apoptotic therapy.