Combating Multidrug Resistance through an NIR-Triggered Cyanine-Containing Amphiphilic Block Copolymer.
Jia TianChao XiaoBaoxuan HuangXiaoze JiangHongliang CaoFeng LiuHongman ZhangPublished in: ACS applied bio materials (2019)
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.
Keyphrases
- drug release
- drug delivery
- cancer therapy
- coronary artery disease
- percutaneous coronary intervention
- photodynamic therapy
- acute coronary syndrome
- acute myocardial infarction
- high throughput
- st elevation myocardial infarction
- aqueous solution
- antiplatelet therapy
- atrial fibrillation
- squamous cell carcinoma
- oxidative stress
- high speed
- single molecule
- molecular dynamics
- heart failure
- mass spectrometry
- squamous cell
- young adults
- left ventricular
- single cell
- drug discovery
- ionic liquid
- fluorescence imaging
- quantum dots
- human health