Proton-Driven Transformable 1 O 2 -Nanotrap for Dark and Hypoxia Tolerant Photodynamic Therapy

• Published in: Advanced science 2022-06, Vol.9 (17), p.e2200128
• Main Authors: Chen, Dapeng, Dai, Hanming, Wang, Weili, Cai, Yu, Mou, Xiaozhou, Zou, Jianhua, Shao, Jinjun, Mao, Zhengwei, Zhong, Liping, Dong, Xiaochen, Zhao, Yongxiang
• Format: Article
• Language: English
• Subjects: Humans; Hypoxia; Photochemotherapy; Photosensitizing Agents - pharmacology; Protons; Tumor Hypoxia
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202200128

Despite the clinical potential, photodynamic therapy (PDT) relying on singlet oxygen ( O ) generation is severely limited by tumor hypoxia and endosomal entrapment. Herein, a proton-driven transformable O -nanotrap (ANBDP NPs) with endosomal escape capability is presented to improve hypoxic tumor PDT. In the acidic endosomal environment, the protonated O -nanotrap ruptures endosomal membranes via a "proton-sponge" like effect and undergoes a drastic morphology-and-size change from nanocubes (≈94.1 nm in length) to nanospheres (≈12.3 nm in diameter). Simultaneously, anthracenyl boron dipyrromethene-derived photosensitizer (ANBDP) in nanospheres transforms to its protonated form (ANBDPH) and switches off its charge-transfer state to achieve amplified O photogeneration capability. Upon 730 nm photoirradiation, ANBDPH prominently produces O and traps generated- O in the anthracene group to form endoperoxide (ANOBDPH). Benefitting from the hypoxia-tolerant O -release property of ANOBDPH in the dark, the O -nanotrap brings about sustained therapeutic effect without further continuous irradiation, thereby achieving remarkable antitumor performance.