Ratiometric singlet oxygen self-detecting and oxygen self-supplying nanosensor for real-time photodynamic therapy feedback and therapeutic effect enhancement.

Integration of singlet oxygen (O) 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 O self-detection, O self-supply and enhanced phototherapy. PAPD nanosensor is constructed by encapsulating anthracene-based O 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 O reference fluorescence (FL) agent and photosensitizer. Once PCN-224-induced O is synthesized, the dual-channel ratiometric FL signal of PAPD actualizes sensitive, accurate and dynamic O visualization and gives real-time therapeutic information correlated with the therapeutic progression. Additionally, the catalase-like activity of PAPD possesses in situ O production via intracellular HO decomposition and accelerates O yields for amplifying the tumor cell killing efficiency. Moreover, the ratiometric O self-detection affords the capacity to evaluate the O 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.