Photoactivated hydroxyl radical generators with highly efficient charge separation for oxygen-independent photodynamic therapy
The design of photosensitizers that generate hydroxyl radicals (·OH) from water and achieve efficient charge separation (CS) is critical for hypoxic tumor photodynamic therapy (PDT). However, such ·OH photo-generators are scarcely reported, particularly those based on simple D-π-A scaffolds. This work presents TPE-SPyCx@BSA, constructed via co-assembly of a series of D-π-A tetraphenylpyridine salts (TPE-SPyCx) with bovine serum albumin (BSA), which initiates photocatalytic water oxidation to ·OH and enables efficient charge separation for oxygen-independent PDT. Electron paramagnetic resonance (EPR) trapping confirmed high-efficiency ·OH generation, and isotope tracing experiments revealed that the oxygen source of ·OH originates exclusively from H2O. The calculated valence band (VB) potential of TPE-SPyCx@BSA meets the thermodynamic conditions for ·OH production via water oxidation. Transient absorption spectra deciphered that the charge-separated state is realized after co-assembly, ensuring electron transfer to generate ·OH via an oxygen-independent pathway. TPE-SPyCx@BSA exhibited superb photocytotoxicity even under severe anoxic conditions and excellent antitumor efficacy in in vivo mouse models. This work provides a strategy for constructing oxygen-independent photodynamic agents, opening an avenue for effective PDT against hypoxic tumors.