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

Yang, C (Yang, Chun) 1Su, MH (Su, Meihui) 1Luo, P (Luo, Pei) 1Liu, YA (Liu, Yanan) 1Yang, F (Yang, Feng) 1Li, CH (Li, Changhua) 1

SMALL, 2021, Article Number: 2101180

DOI: 10.1002/smll.202101180

Abstract

Photodynamic therapy (PDT), which utilizes photosensitizer to convert molecular oxygen into singlet oxygen (O-1(2)) 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 O-1(2) 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 O-1(2), An-NP consists of two other key components: a molecularly designed anthracene derivative capable of trapping/releasing O-1(2) with superior reversibility and a dye J-aggregate with superb photothermal performance. Thus, in 655 nm laser-triggered PDT process, An-NP generates abundant O-1(2) with extra O-1(2) 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 O-1(2) and regenerates An-NP. The intratumoral oxygen level can be replenished during the PTT cycle for the next round of PDT to generate O-1(2). The working principle and phototherapy efficacy are preliminarily demonstrated in living cells and tumor-bearing mice, respectively.