Ruthenium(II) complexes coordinated to graphitic carbon nitride: Oxygen self-sufficient photosensitizers which produce multiple ROS for photodynamic therapy in hypoxia.

Abstract

The photodynamic therapy (PDT) of cancer is limited by tumor hypoxia as PDT efficiency depends on O₂ concentration. A novel oxygen self-sufficient photosensitizer (Ru-g-C₃N₄) was therefore designed and synthesized via a facile one-pot method in order to overcome tumor hypoxia-induced PDT resistance. The photosensitizer is based on [Ru(bpy)₂]²⁺ coordinated to g-C₃N₄ nanosheets by Ru-N bonding. Compared to pure g-C₃N₄, the resulting nanosheets exhibit increased water solubility, stronger visible light absorption, and enhanced biocompatibility. Once Ru-g-C₃N₄ is taken up by hypoxic tumor cells and exposed to visible light, the nanosheets not only catalyze the decomposition of H₂O₂ and H₂O to generate O₂, but also catalyze H₂O₂ and O₂ concurrently to produce multiple ROS (^•OH, ^•O₂^-, and ¹O₂). In addition, Ru-g-C₃N₄ affords luminescence imaging, while continuously generating O₂ to alleviate hypoxia greatly improving PDT efficacy. To the best of our knowledge, this oxygen self-sufficient photosensitizer produced via grafting a metal complex onto g-C₃N₄ is the first of its type to be reported.