|
Photoactivatable Ru complexes are multifunctional compounds: (i) they have similar anticancer effects as cisplatin; (ii) they are photocleavable; (iii) they can sensitize the generation of singlet oxygen for photodynamic therapy. However, they are easily cleaned from blood stream, instable in biological environments, and may not efficiently inhibit tumor growth in hypoxic environments. To solve these problems, we design Ru-containing polymers for deep-tissue phototherapy. In this talk, I will present the synthesis of block copolymers (BCPs) that contain photoactivatable Ru moieties and their photo-controlled anticancer effect. First, we synthesized Ru-containing BCPs, in which Ru moieties act as photocleavable moieties, singlet oxygen sensitizers, and anticancer agents. Depending on the molecular weights and chemical structures, the BCPs assembled into micelles, vesicles, large compound micelles and other nanostructures. The BCP assemblies can circulate in blood stream, accumulate at tumor sites via the EPR effect, and be taken up by cancer cells. Red light passed through tissue and activated the Ru-containing BCP assemblies. The photoactivated Ru complexes and generated singlet oxygen inhibited the growth of cancer cells. We demonstrated anticancer activities of the photoactivatable Ru-containing BCPs in vitro and in vivo. In addition, we designed Ru-containing BCPs against hypoxic tumors. The BCPs, which contain photocleavable drug-Ru complex conjugates, self-assembled into micelles. The micelles are biocompatible and carried the conjugates into tumor cells. Subsequent red light irradiation induced intracellular release of the drug-Ru complex conjugates. Because the photoinduced release is oxygen-independent, the novel polymer provides a new platform for phototherapy against hypoxic tumors in vivo.
|
