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.