Intratumoral Synthesis of Two-Photon NIR-I Activated Photosensitizer Undergoing Oxygen-Free Photo-Redox Cycle for
Yingyong Ni1, Ting Wang1, Xuan Zhao1
1School of Chemistry and Chemical Engineering, School of Materials Science and Engineering, School of Chemistry and Chemical Engineering, Institutes of Physical Science and Information Technology, Center of Free Electron Laser & High Magnetic Field, Key Laboratory of Structure and Functional Regulation of Hybrid Materials Ministry of Education, Key Laboratory of Functional Inorganic Materials Chemistry of Anhui Province, Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials of Anhui Province, Anhui University, Hefei, 230601, P. R. China.
Abstract:
The design of NIR-I activated oxygen-independent photosensitizers with optimal delivery efficiency holds great promise in efficient photodynamic therapy of deep-seated hypoxic tumors. Herein, by fabricating intratumoral synthetic therapeutic system, the silenced prodrug AICST are selectively and spontaneously transformed into AICST-SO3 with NIR-I absorption, which underwent oxygen-free photo-redox cycle for hypoxic tumor phototherapy. The prodrug AICST based on D-π-A structure with a two-photon moiety coumarin as donor (D), C═C bond as π bridge, and indole derivative as electron acceptor (A) responded to the intracellular overexpressed SO3 2- to yield photosensitizer AICST-SO3. The photo-excited AICST-SO3 generated charge separation species, wherein the strong oxidized moiety would capture electron from water to generate cytotoxic hydroxyl radical (OH•), and the anionic radicals transferred electrons to pyruvic acid to accomplish the photo-redox cycle. In vitro cellular experiments confirmed the intracellular synthesis of AICST-SO3 and the efficient cancer cells killing capability. In vivo mouse model experiments revealed that, under the 800 nm irradiation, the tumor can almost be completely ablated by the prodrug AICST, further confirming the great advance of the intratumoral synthetic therapeutic system activated by NIR-I light for hypoxic tumor therapy. This work offers new pathway for developing a potent phototherapy model.
