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

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 H2O into O2 upon the same laser irradiation. In addition, the inherent catalase (CAT)-like activity of PdCu NYs enables photo-enzyme dual-catalytic O2 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.