Reversibly sensitizing-storing-releasing 1 O 2 within a single platinum(II)-acetylide-based metallacycle molecule via laser power modulation

Tumor hypoxia severely limits the therapeutic efficacy of photodynamic therapy (PDT) for solid tumors, which is highly dependent on tissue oxygen concentration. In this study, we developed a platinum(II)-acetylide-based metallacycle compound bearing six 1,4-dimethylnaphthalenes (DMN) groups, and controlled the photodynamic and photothermal effects of the compound by adjusting the power of 730 nm laser to achieve reversible sensitization, storage and release of 1 O 2 within a single molecule. The compound formed nanoparticles by self-assembly and exhibited good water solubility and biocompatibility. Under laser irradiation, the strong spin-orbit coupling of platinum atoms in the metallacycle facilitated 1 O 2 generation. The produced 1 O 2 was captured by the DMN carriers and transported into the hypoxic tumor, where 1 O 2 release was triggered owing to the good photothermal effect of the extended conjugation of the metallacycle. During therapy, the metallacycle serving as a photosensitizer, 1 O 2 carrier, and photothermal reagent, achieved the synergistic therapy of PDT/PTT, demonstrating the versatility of the metallacycle. This study proposes a new strategy to develop phototherapy agents that are suitable for hypoxic tumors.