Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering, and Materials Science, Soochow University, Suzhou, 215123, People's Republic of China.
Biomacromolecules. 2013 Jul 8;14(7):2411-9. doi: 10.1021/bm400530d. Epub 2013 Jun 4.
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.
金纳米棒核可生物降解胶束通过在金纳米棒（AuNRs）表面包覆脂化聚乙二醇-b-聚（ε-己内酯）（PEG-PCL-LA）嵌段共聚物来制备，并研究了其对阿霉素（DOX）的远程触发释放和对敏感和多药耐药（MDR）癌细胞的有效抑制作用。胶束具有均匀的尺寸和优异的胶体稳定性。体外释放研究表明，载 DOX 的 AuNR 核胶束（AuNR-M-DOX）在生理条件下的药物释放最小，但在低功率密度 0.2 W/cm2 的近红外辐射下显著增强，这很可能是由于 PCL 相的光热诱导相变。共聚焦显微镜和流式细胞术表明，近红外光也可以触发敏感和耐药 MCF-7 细胞中有效释放 DOX。MTT 分析表明，温和的近红外辐射显著增强了 AuNR-M-DOX 对敏感 MCF-7 细胞的抗肿瘤活性，达到了与游离 DOX 相当的水平。最显著的是，AuNR-M-DOX 联合近红外辐射还可以有效杀死耐药 MCF-7 细胞，在 DOX 剂量为 10 μg equiv/mL 时观察到细胞存活率为 38%，而在相同条件下用游离 DOX 处理的细胞保持 100%的细胞存活率。这些具有高稳定性、光触发药物释放和有效逆转癌细胞多药耐药性的金纳米棒核可生物降解胶束已成为一种新的靶向癌症治疗平台。
