A benzophenoxazine-dyad as cancer indicator using for fluorescence-guided phototherapy

ABSTRACT Clinically, phototherapy is adapted to tumors in semi-enclosed location, such as cervical, head & neck and gastric cancer, using optical fibers to introduce light. Different with general photodynamic therapy, it has special demands of tumor recognition and lower light dose. However, a merge of primary photosensitizer (ALA et.al) and magnetic resonance (or ultrasound) imaging is commonly used in the therapeutic mode, having low efficacy and complicated operation. To realize a fluorescence-guided phototherapy, here we designed a benzophenoxazine-dyad photosensitizer, namely NBS-NBSe, firstly realize a dyad-caused quenching (DCQ) method to regulate the fluorescence of benzophenoxazine as cancer indicator. The DCQ of NBS-NBSe drastically decrease the fluorescence of benzophenothiazine (NBS), while glutathione in cancer can efficiently release the fluorescence (9.3-fold) to guide the optical source in phototherapy. Meanwhile, the high singlet oxygen generation of benzophenoselenzinium (NBSe) provide an efficient photo ablation ability, and the NBS of anti-hypoxia can assist the therapy of hypoxia deep-seated tumors to reduce tumor recurrence. Under the low light dose of 2.4 J/cm2, NBS-NBSe showed excellent therapeutic efficacy toward tumor cells (24-fold than chlorins e6). The fluorescence recognition ability between tumor/normal cells and the powerful phototoxicity ensure the fluorescence-guided therapeutic mode using for these tumors.