Proton‐Driven Transformable <sup>1</sup>O<sub>2</sub>‐Nanotrap for Dark and Hypoxia Tolerant Photodynamic Therapy
Dapeng Chen, Hanming Dai, Weili Wang, Yu Cai, Xiaozhou Mou, Jianhua Zou, Jinjun Shao, Zhengwei Mao, Liping Zhong, Xiaochen Dong, Yongxiang Zhao
Abstract
Abstract Despite the clinical potential, photodynamic therapy (PDT) relying on singlet oxygen ( 1 O 2 ) generation is severely limited by tumor hypoxia and endosomal entrapment. Herein, a proton‐driven transformable 1 O 2 ‐nanotrap (ANBDP NPs) with endosomal escape capability is presented to improve hypoxic tumor PDT. In the acidic endosomal environment, the protonated 1 O 2 ‐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 1 O 2 photogeneration capability. Upon 730 nm photoirradiation, ANBDPH prominently produces 1 O 2 and traps generated‐ 1 O 2 in the anthracene group to form endoperoxide (ANOBDPH). Benefitting from the hypoxia‐tolerant 1 O 2 ‐release property of ANOBDPH in the dark, the 1 O 2 ‐nanotrap brings about sustained therapeutic effect without further continuous irradiation, thereby achieving remarkable antitumor performance.