Hydroxyl-tunable type I photosensitizer based on curcumin for photodynamic therapy against hypoxic tumor cells

The development of effective approaches to design type-I photosensitizers is of great importance due to their less oxygen content dependency. In this work, we report a simple strategy for the preparation of type-I photosensitizer (CNOH) by introducing two hydroxyl groups into the type-II photosensitizer (CN). Hydroxyl is not only an electron-donating group but can also form hydrogen bonds, affecting the energy levels and polarity of the photosensitizer. The results indicated that the small ΔE_S1-T1 and substantial reduction potential of CNOH might facilitate electron transfer to generate superoxide anions through type I process. Additionally, compared with the dual organelle-targeted photosensitizer CN, CNOH only exhibited endoplasmic reticulum targeting due to the weaker lipophilicity of CNOH. Under hypoxic conditions, CNOH showed stronger phototoxicity to tumor cells than CN, making it more suitable for PDT in hypoxic tumors. This provides a new direction for the design of type I photosensitizers.