Oxygen Concentration Effect in Photosensitized Generation of ¹O₂ from Normoxia to Hypoxia

Photodynamic therapy (PDT) has gained widespread acceptance as a clinical cancer treatment modality and has been attracting intensive attention on developing novel PDT strategies. However, the hypoxic environment in tumors is considered as a significant challenge for efficient type II PDT, based on the inference of the highly oxygen-concentration-related ¹O₂ generation. Contrary to this conventional understanding, our research demonstrates oxygen concentration independence in the photosensitized generation of ¹O₂, as evidenced through steady-state and transient spectroscopy for chlorin e6 and methylene blue from normoxic to hypoxic conditions. We propose an oxygen-concentration-independent kinetic model, suggesting that efficient ¹O₂ generation can take place as long as the triplet-state lifetime ratio of the photosensitizer (τ_h/τ_n) is in a similar range to pO₂ⁿ/pO₂^h. Our findings provide insights into PDT mechanisms and indicate that the oxygen concentration reduction concerns may not be critical for effective PDT in hypoxic tumor environments.