Ratiometric singlet oxygen self-detecting and oxygen self-supplying nanosensor for real-time photodynamic therapy...

Integration of singlet oxygen (¹O₂) detection that provides necessary therapeutic feedback into nanotheranostics for hypoxic tumor photodynamic therapy (PDT) is desirable but still challenging. Herein, we report a nanosensor (denominated PAPD) by combining dual-channel ratiometric sensing and oxygen-augmenting strategies, which synergistically realizes real-time ¹O₂ self-detection, O₂ self-supply and enhanced phototherapy. PAPD nanosensor is constructed by encapsulating anthracene-based ¹O₂ sensitive fluorophore (DPA) into porphyrin metal-organic frameworks (PCN-224), decorating gold nanoparticles (AuNPs) as nanoenzymes, and coating polyethylene glycol thiol (PEG-SH) by the Au-S bond. PCN-224 serves as ¹O₂ reference fluorescence (FL) agent and photosensitizer. Once PCN-224-induced ¹O₂ is synthesized, the dual-channel ratiometric FL signal of PAPD actualizes sensitive, accurate and dynamic ¹O₂ visualization and gives real-time therapeutic information correlated with the therapeutic progression. Additionally, the catalase-like activity of PAPD possesses in situ O₂ production via intracellular H₂O₂ decomposition and accelerates ¹O₂ yields for amplifying the tumor cell killing efficiency. Moreover, the ratiometric ¹O₂ self-detection affords the capacity to evaluate the O₂ self-supplying effect in tumor 4T1 cells. Consequently, the rational-designed nanosensor PAPD provides a paradigm for real-time therapeutic evaluation and precise hypoxic tumor treatment clinically.