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

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