Red-Light-Responsive Polypeptoid Nanoassemblies Containing a Ruthenium(II) Polypyridyl Complex with Synergistically Enhanced Drug Release and ROS Generation for Anticancer Phototherapy
Yandong Ma, Zhihua Zhang, Fan Sun, Pierre Mesdom, Xin Ji, Pierre Bürckel, Gilles Gasser, Min‐Hui Li
Abstract
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.