Oxygen Concentration\nEffect in Photosensitized Generation\nof <sup>1</sup>O<sub>2</sub> from Normoxia to Hypoxia

Photodynamic therapy (PDT) has gained widespread acceptance\nas\na clinical cancer treatment modality and has been attracting intensive\nattention on developing novel PDT strategies. However, the hypoxic\nenvironment in tumors is considered as a significant challenge for\nefficient type II PDT, based on the inference of the highly oxygen-concentration-related <sup>1</sup>O<sub>2</sub> generation. Contrary to this conventional understanding,\nour research demonstrates oxygen concentration independence in the\nphotosensitized generation of <sup>1</sup>O<sub>2</sub>, as evidenced\nthrough steady-state and transient spectroscopy for chlorin e6 and\nmethylene blue from normoxic to hypoxic conditions. We propose an\noxygen-concentration-independent kinetic model, suggesting that efficient <sup>1</sup>O<sub>2</sub> generation can take place as long as the triplet-state\nlifetime ratio of the photosensitizer (τ<sub>h</sub>/τ<sub>n</sub>) is in a similar range to pO<sub>2</sub><sup>n</sup>/pO<sub>2</sub><sup>h</sup>. Our findings provide insights into PDT mechanisms\nand indicate that the oxygen concentration reduction concerns may\nnot be critical for effective PDT in hypoxic tumor environments.