Supramolecular metallopolymer for hypoxia-activated ruthenium complexes delivery and smart chemo-photodynamic therapy

The Ru complexes have garnered a great deal of attention for antitumor phototherapy; however, achieving efficient cellular uptake and tumor-specific activation represents a major challenge. Herein, we synthesize a hypoxia-activated Ru complex (RuANM) and construct it into supramolecular polymers (PolyRuANM) through high binding affinity interaction. The amphiphilic supramolecular polymers possess self-assembly, resulting in the formation of diverse nanostructures exhibiting a range of morphologies by simply adjusting the host-guest ratio. As the polymer nanostructure size and morphology have been optimized, PolyRuANM prevents premature drug leakage and accumulates rapidly in the tumor cells. In the tumor hypoxia microenvironment, the polymer undergoes selective activation and disintegration, leading to the unlock of Ru complexes. Notably, the subsequent application of red light irradiation exacerbates the hypoxia and potentiates the liberation of the Ru complexes. This polymer design concept provides some novel insights into on-demand drug delivery and smart chemophotodynamic therapy.