Red-Light-Responsive Polypeptoid Nanoassemblies Containing a Ruthenium(II) Polypyridyl Complex with Synergistically Enhanced Drug Release and ROS Generation for Anticancer Phototherapy.

Polymer micelles/vesicles made of a red-light-responsive Ru(II)-containing block copolymer (PolyRu) are elaborated as a model system for anticancer phototherapy. PolyRu is composed of PEG and a hydrophobic polypeptoid bearing thioether side chains, 40% of which are coordinated with [Ru(2,2':6',2″-terpyridine)(2,2'-biquinoline)](PF 6 ) 2 via the Ru-S bond, resulting in a 67 wt % Ru complex loading capacity. Red-light illumination induces the photocleavage of the Ru-S bond and produces [Ru(2,2':6',2″-terpyridine)(2,2'-biquinoline)(H 2 O)](PF 6 ) 2 . Meanwhile, ROS are generated under the photosensitization of the Ru complex and oxidize hydrophobic thioether to hydrophilic sulfoxide, causing the disruption of micelles/vesicles. During the disruption, ROS generation and Ru complex release are synergistically enhanced. PolyRu micelles/vesicles are taken up by cancer cells while they exhibit very low cytotoxicity in the dark. In contrast, they show much higher cytotoxicity under red-light irradiation. PolyRu micelles/vesicles are promising nanoassembly prototypes that protect metallodrugs in the dark but exhibit light-activated anticancer effects with spatiotemporal control for photoactivated chemotherapy and photodynamic therapy.