A near-infrared fluorescent-photoacoustic nanoprobe for tumor targeted photodynamic–photothermal therapy

Abstract

Cancer phototherapy has emerged as a promising noninvasive modality with natural and precise spatiotemporal control for oncology. However, conventional photosensitizers are often limited by insufficient reactive oxygen species (ROS) generation, hypoxia-compromised efficacy, modest photothermal conversion, and/or off-target phototoxicity. To address these challenges, we develop a novel NIR fluorescent nanoprobe, PCB NPs, which self-assemble into ∼40 nm spherical particles featuring an emission maximum at 950 nm with a tail extending to 1200 nm, thereby enabling deep-tissue penetration and high-resolution imaging. Notably, this nanoprobe demonstrates excellent tumor-targeting capability, achieving tumor accumulation within just 6 hours post-intravenous administration as confirmed by in vivo NIR fluorescence and photoacoustic imaging. Under 808 nm light irradiation, PCB NPs simultaneously activate a type I pathway to generate superoxide anion O₂˙⁻, and achieve 49.96% photothermal conversion efficiency. Theoretical calculations atomistically elucidate the mechanisms underlying the superior photothermal conversion and excellent photostability of PCB. The combined photodynamic and photothermal effects lead to promoted lymphocyte infiltration and aggravate intratumoral hypoxia and overcome cellular thermotolerance mechanisms, which successfully results in a pronounced 99.34% tumor growth inhibition without discernible histopathological damage to major organs or changes in body weight. These findings establish PCB NPs as a promising platform for next-generation precision cancer phototherapy, integrating rapid tumor targeting, deep-tissue imaging, hypoxia-resilient ROS generation, and potent photodynamic–photothermal effects within a single nanoprobe.