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

Abstract Despite the clinical potential, photodynamic therapy (PDT) relying on singlet oxygen (1O2) generation is severely limited by tumor hypoxia and endosomal entrapment. Herein, a proton‐driven transformable 1O2‐nanotrap (ANBDP NPs) with endosomal escape capability is presented to improve hypoxic tumor PDT. In the acidic endosomal environment, the protonated 1O2‐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 1O2 photogeneration capability. Upon 730 nm photoirradiation, ANBDPH prominently produces 1O2 and traps generated‐1O2 in the anthracene group to form endoperoxide (ANOBDPH). Benefitting from the hypoxia‐tolerant 1O2‐release property of ANOBDPH in the dark, the 1O2‐nanotrap brings about sustained therapeutic effect without further continuous irradiation, thereby achieving remarkable antitumor performance.