Department of Polymer Science & Engineering, School of Chemistry & Chemical Engineering, Shanghai Jiao Tong University , Shanghai 200240, P. R. China.
Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University , Shanghai 200240, P. R. China.
Biomacromolecules. 2016 Jul 11;17(7):2489-501. doi: 10.1021/acs.biomac.6b00721. Epub 2016 Jun 24.
To integrate cocktail chemotherapy with photothermal therapy into one biocompatible and biodegradable nanocarrier, the plasmonic, lactose-targeted, and dual anticancer drugs-loaded polypeptide composite nanoparticles were for the first time fabricated under mild conditions. The glyco-PEGylated polypeptide micelles that self-assembled from the lactose (LAC) and PEG grafted polycysteine terpolymer were used as templates to generate the plasmonic composite nanoparticles, as mainly characterized by DLS, TEM, SEM, and XPS. These composite nanoparticles showed a broad and strong near-infrared (NIR) absorption at 650-1100 nm and increased the temperature of phosphate buffer solution by 30.1 °C upon a continuous-wave laser irradiation (808 nm, 5 min, 2 W·cm(-2)), while the same dose of NIR-mediated heating completely killed HepG2 cancer cells in vitro, presenting excellent photothermal properties. Two anticancer drugs, doxorubicin (DOX) and 6-mercaptopurine (6-MP), were loaded into the composite nanoparticles through physical interactions and Au-S bond, respectively. The dual drugs-loaded composite nanoparticles exhibited reduction-sensitive and NIR-triggered cocktail drugs release profiles and trigger-enhanced cytotoxicity. As evidenced by flow cytometry, fluorescence microscopy, and MTT assay, the LAC-coated composite nanoparticles were more internalized by the HepG2 than the HeLa cell line, demonstrating a LAC-targeting enhanced cytotoxicity toward HepG2. The combination cocktail chemo-photothermal therapy produced a lower half maximal inhibitory concentration than cocktail chemotherapy or photothermal therapy alone, displaying a good synergistic antitumor effect.
为了将鸡尾酒化疗与光热疗法整合到一个生物相容和可生物降解的纳米载体中，首次在温和条件下制备了等离子体、乳糖靶向和双重抗癌药物负载的多肽复合纳米粒子。由乳糖（LAC）和 PEG 接枝聚半胱氨酸三嵌段共聚物自组装而成的糖基-PEG 化多肽胶束被用作模板来生成等离子体复合纳米粒子，主要通过 DLS、TEM、SEM 和 XPS 进行表征。这些复合纳米粒子在 650-1100nm 处表现出宽而强的近红外（NIR）吸收，并在连续波激光照射（808nm，5min，2W·cm(-2)）下将磷酸盐缓冲溶液的温度升高 30.1°C，而相同剂量的 NIR 介导加热可完全杀死体外 HepG2 癌细胞，表现出优异的光热性能。两种抗癌药物阿霉素（DOX）和 6-巯基嘌呤（6-MP）通过物理相互作用和 Au-S 键分别装载到复合纳米粒子中。负载双重药物的复合纳米粒子表现出还原敏感和 NIR 触发的鸡尾酒药物释放谱和触发增强的细胞毒性。如流式细胞术、荧光显微镜和 MTT 测定所示，LAC 涂层的复合纳米粒子比 HeLa 细胞系更容易被 HepG2 内化，表明 LAC 靶向增强了对 HepG2 的细胞毒性。组合鸡尾酒化疗-光热疗法产生的半最大抑制浓度低于鸡尾酒化疗或光热疗法单独治疗，显示出良好的协同抗肿瘤作用。
