Gold Nanorod-Cored Biodegradable Micelles as a Robust and Remotely Controllable Doxorubicin Release System for Potent Inhibition of Drug-Sensitive and -Resistant Cancer Cells
Yinan Zhong †, Chao Wang ‡, Liang Cheng ‡, Fenghua Meng †, Zhiyuan Zhong *†（钟志远）, and Zhuang Liu *‡ (刘庄)
† Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering, and Materials Science, Soochow University, Suzhou, 215123, People’s Republic of China
‡ Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, 215123, People’s Republic of China
Biomacromolecules, 2013, 14 , 2411–2419.
Gold nanorod-cored biodegradable micelles were prepared by coating gold nanorods (AuNRs) with lipoylated poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL-LA) block copolymer and investigated for remotely triggered release of doxorubicin (DOX) and effective inhibition of drug-sensitive and multidrug-resistant (MDR) cancer cells. The micelles had uniform sizes and excellent colloidal stability. The in vitro release studies showed that drug release from DOX-loaded AuNR-cored micelles (AuNR-M-DOX) was minimal under physiological conditions but markedly enhanced upon NIR irradiation at a low power density of 0.2 W/cm2, most likely due to photothermally induced phase transition of PCL regime. As revealed by confocal microscopy and flow cytometry, NIR could also trigger effective DOX release in drug-sensitive as well as drug-resistant MCF-7 cells. MTT assays showed that antitumor activity of AuNR-M-DOX to drug-sensitive MCF-7 cells was significantly boosted by mild NIR irradiation, reaching a comparable level to free DOX. Most remarkably, AuNR-M-DOX combined with NIR irradiation could also effectively kill drug-resistant MCF-7 cells, in which a cell viability of 38% was observed at a DOX dosage of 10 μg equiv/mL, whereas 100% cell viability was maintained for cells treated with free DOX under otherwise the same conditions. These AuNR-cored biodegradable micelles with high stability, photo-triggered drug release, and effective reversal of multidrug resistance in cancer cells have appeared as a novel platform for targeted cancer therapy.
链接： http://pubs.acs.org/doi/abs/10.1021/bm400530d