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首页> 外文期刊>Biomacromolecules >Plasmonic, Targeted, and Dual Drugs-Loaded Polypeptide Composite Nanoparticles for Synergistic Cocktail Chemotherapy with Photothermal Therapy
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Plasmonic, Targeted, and Dual Drugs-Loaded Polypeptide Composite Nanoparticles for Synergistic Cocktail Chemotherapy with Photothermal Therapy

机译：血浆，靶向和双重药物的多肽复合纳米粒子用于光热疗法的协同鸡尾酒化学疗法。

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To integrate cocktail chemotherapy with photo thermal 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 degrees 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.
机译：为了将鸡尾酒疗法与光热疗法整合到一个生物相容且可生物降解的纳米载体中，首次在温和条件下制备了负载等离子体，乳糖靶向和双重抗癌药物的多肽复合纳米颗粒。由乳糖（LAC）和PEG接枝的多半胱氨酸三元共聚物自组装而成的糖聚乙二醇化多肽胶束被用作模板来生成等离子体复合纳米颗粒，其主要特征在于DLS，TEM，SEM和XPS。这些复合纳米颗粒在650-1100 nm处显示出宽而强的近红外（NIR）吸收，并且在连续波激光辐照（808 nm，5 min，2 W.cm）下使磷酸盐缓冲液的温度升高30.1摄氏度。 （-2）），尽管相同剂量的NIR介导的加热在体外完全杀死了HepG2癌细胞，但仍具有出色的光热特性。通过物理相互作用和Au-S键将两种抗癌药物阿霉素（DOX）和6-巯基嘌呤（6-MP）分别加载到复合纳米颗粒中。载有双重药物的复合纳米颗粒显示出还原敏感性和近红外触发的鸡尾酒药物释放曲线和增强的细胞毒性。如通过流式细胞术，荧光显微镜和MTT分析所证明的，与HeLa细胞系相比，HepG2将LAC包被的复合纳米颗粒内在化，表明LAC靶向针对HepG2的增强的细胞毒性。鸡尾酒化学-光热疗法的组合产生的最大抑制浓度低于单独的鸡尾酒化学疗法或光热疗法，显示出良好的协同抗肿瘤作用。

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