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

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.