A Renal Clearable Nano‐Assembly with Förster Resonance Energy Transfer Amplified Superoxide Radical and Heat Generation to Overcome Hypoxia Resistance in Phototherapeutics

Abstract

AbstractGiven that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light‐harvesting ability not only amplifies superoxide radical (O2•‐) production but also promotes heat generation upon near‐infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced.