A Single NIR‐II Laser‐Triggered Self‐Enhancing Photo/Enzyme‐coupled Three‐in‐One Nanosystems for Breast Cancer Phototheranostics

Abstract Multifunctional phototheranostics, employing precise and non‐invasive techniques, is widely developed to enhance theranostic efficiency of breast cancer (BC), reduce side‐effects, and improve quality of life. Integrating all phototheranostic modalities into a single photosensitizer for highly effective BC treatment is particularly challenging due to the potential inefficiency and time consumption associated with repeated switching of multiple‐wavelength lasers. Herein, a novel single NIR‐II laser‐triggered three‐in‐one nanosystem(PdCu NY) is rationally designed, which enables dual‐modal (NIR‐II FL/NIR‐II PA) imaging‐guided self‐enhancing photothermal‐photodynamic therapy (PTT‐PDT) in NIR‐II window. The PdCu NY based on optimal Pd/Cu molar‐ratio(1:11) can be easily fabricated and large‐scale production for simultaneous PTT‐PDT against BC under a single 1064nm laser irradiation. Significantly, the PdCu NY acted as a promising photocatalyst for decomposition of H 2 O into O 2 upon the same laser irradiation. In addition, the inherent catalase (CAT)‐like activity of PdCu NYs enables photo‐enzyme dual‐catalytic O 2 supply to effectively alleviate hypoxia, achieving self‐enhanced PDT efficiency. These PTT‐PDT self‐enhanced nanosystems demonstrate precise lesion localization and complete tumor ablation using a single 1064nm laser source by “one‐laser, multi‐functions” strategy. More importantly, this study not only reports a three‐in‐one PdCu‐based phototheranostic agent, but also sheds light on the exploration of versatile biosafety nanosystems for clinical applications.