Combating Multidrug Resistance through an NIR-Triggered Cyanine-Containing Amphiphilic Block Copolymer

Nowadays, multidrug resistance is the main challenge during cancer chemotherapy. Photochemical internalization (PCI) has been demonstrated to be a unique and promising approach to overcome multidrug resistance with light-harnessed activation. Here, an amphiphilic pH-responsive block copolymer with IR780 at the junction point [PEG-IR780-PDEAEMA; PEG, poly­(ethylene glycol); PDEAEMA, poly­((diethylamino)­ethyl methacrylate)] has been designed as a perfect drug release platform as well as a functional macromolecular photosensitizer of PCI. PEG-IR780-PDEAEMA was synthesized by the combination of RAFT polymerization and click chemistry and further self-assembled into spherical micelles in aqueous solution. Notably, IR780 moieties were dispersed regularly around the core of the spherical micelles, which led to the diminishment of the aggregation-caused quenching effect of photosensitizers and high singlet oxygen quantum yield. Confocal laser scanning microscopy results showed that a high amount of doxorubicin (DOX) was translocated into the nucleus with NIR light irradiation through the PCI effect. Moreover, DOX-loaded PEG-IR780-PDEAEMA micelles showed much higher phototoxicity under short-time NIR light irradiation than their dark toxicity. Therefore, this DOX-loaded drug release platform based on pH-sensitive IR780-containing block copolymers has the potential to offer an efficient strategy for addressing drug resistance.