Singlet Oxygen “Afterglow” Therapy with NIR‐II Fluorescent Molecules

Abstract Improving singlet oxygen ( 1 O 2 ) lifespan by fractionated delivery in dark and hypoxic conditions is a better way to achieve enhanced phototherapeutic efficacy. Herein, three boron dipyrromethene (BODIPY) dyes are synthesized to demonstrate that anthracence‐functionalized BODIPY, namely ABDPTPA is an efficient heavy‐atom‐free photosensitizer for the reversible capture and release of 1 O 2 . The spin–orbit charge‐transfer intersystem crossing of ABDPTPA promises a high 1 O 2 quantum yield of 60% in dichloromethane. Under light irradiation, the anthracene group reacts with 1 O 2 to produce endoperoxide. Interestingly, after termination of irradiation, the endoperoxide undergoes thermal cycloreversion to produce 1 O 2 , and regenerates the anthracene module to achieve 1 O 2 “afterglow,” which results in a prolonged half lifetime of 1 O 2 for 9.2 min. In vitro cytotoxicity assays indicate that ABDPTPA nanoparticles have a low half‐maximal inhibitory concentration (IC 50 ) of 3.6 µg mL −1 on U87MG cells. Further, the results of near‐infrared‐II fluorescence‐imaging‐guided phototherapy indicate that ABDPTPA nanoparticles can inhibit tumor proliferation even at a low dose (200 µg mL −1 , 100 µL) without any side effects. Therefore, the study provides a generalized 1 O 2 “afterglow” strategy to enhance phototheranostics for complete tumor regression.