Proton-Driven Transformable 1O2-Nanotrap for Dark and Hypoxia Tolerant Photodynamic Therapy

Despite the clinical potential, photodynamic therapy (PDT) relying on singlet oxygen (O-1(2)) generation is severely limited by tumor hypoxia and endosomal entrapment. Herein, a proton-driven transformable O-1(2)-nanotrap (ANBDP NPs) with endosomal escape capability is presented to improve hypoxic tumor PDT. In the acidic endosomal environment, the protonated O-1(2)-nanotrap ruptures endosomal membranes via a proton-sponge like effect and undergoes a drastic morphology-and-size change from nanocubes (approximate to 94.1 nm in length) to nanospheres (approximate to 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-1(2) photogeneration capability. Upon 730 nm photoirradiation, ANBDPH prominently produces O-1(2) and traps generated-O-1(2) in the anthracene group to form endoperoxide (ANOBDPH). Benefitting from the hypoxia-tolerant O-1(2)-release property of ANOBDPH in the dark, the O-1(2)-nanotrap brings about sustained therapeutic effect without further continuous irradiation, thereby achieving remarkable antitumor performance.

Automated summary

In this study, a proton-driven transformable O-1(2)-nanotrap was developed to overcome tumor hypoxia and endosomal entrapment, leading to sustained antitumor performance.