A Photosensitive Polymeric Carrier with a Renewable Singlet Oxygen Reservoir Regulated by Two NIR Beams for Enhanced Antitumor Phototherapy

Abstract Photodynamic therapy (PDT), which utilizes photosensitizer to convert molecular oxygen into singlet oxygen (1O2) upon laser irradiation to ablate tumors, will exacerbate the already oxygen shortage of most solid tumors and is thus self‐limiting. Herein, a sophisticated photosensitive polymeric material (An‐NP) that allows sustained 1O2 generation and sufficient oxygen supply during the entire phototherapy is engineered by alternatively applying PDT and photothermal therapy (PTT) controlled by two NIR laser beams. In addition to a photosensitizer that generates 1O2, An‐NP consists of two other key components: a molecularly designed anthracene derivative capable of trapping/releasing 1O2 with superior reversibility and a dye J‐aggregate with superb photothermal performance. Thus, in 655 nm laser‐triggered PDT process, An‐NP generates abundant 1O2 with extra 1O2 being trapped via the conversion into EPO‐NP; while in the subsequent 785 nm laser‐driven PTT process, the converted EPO‐NP undergoes thermolysis to liberate the captured 1O2 and regenerates An‐NP. The intratumoral oxygen level can be replenished during the PTT cycle for the next round of PDT to generate 1O2. The working principle and phototherapy efficacy are preliminarily demonstrated in living cells and tumor‐bearing mice, respectively.