Selenium-Containing Type-I Organic Photosensitizers with Dual Reactive Oxygen Species of Superoxide and Hydroxyl Radicals as Switch-Hitter for Photodynamic Therapy.

ABSTRACT: Organic type-I photosensitizers (PSs) which produce aggressive reactive oxygen species (ROS) with less oxygen-dependent exhibit attractive curative effect for photodynamic therapy (PDT), as they adapt better to hypoxia microenvironment in tumors. However, the reported type-I PSs are limited and its exacted mechanism of oxygen dependence is still unclear. Herein, new selenium-containing type-I PSs of Se6 and Se5 with benzoselenadiazole acceptor has been designed and possessed aggregation-induced emission characteristic. Benefited from double heavy-atom-effect of selenium and bromine, Se6 shows a smaller energy gap (ΔE_ST ) of 0.03 eV and improves ROS efficiency. Interestingly, type-I radicals of both long-lived superoxide anion (O₂ ^•‾ ) and short-lived hydroxyl (^• OH) are generated from them upon irradiation. This may provide a switch-hitter of dual-radical with complementary lifetimes for PDT. More importantly, simultaneous processes to produce ^• OH are revealed, including disproportionation of O₂ ^•‾ and reaction between excited PS and water. Actually, Se6 displays superior in-vitro PDT performance to commercial chlorin e6 (Ce6), under normoxia or hypoxia. After intravenous injection, a significantly in-vivo PDT performance is demonstrated on Se6, where tumor growth inhibition rates of 99% is higher than Ce6. These findings offer new insights about both molecular design and mechanism study of type-I PSs.

SUBMITTER: Wang H 

PROVIDER: S-EPMC10460872 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature