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多功能 PEG-b-多肽修饰的金纳米棒用于乳腺癌的靶向联合化疗-光热治疗。

Multifunctional PEG-b-polypeptide-decorated gold nanorod for targeted combined chemo-photothermal therapy of breast cancer.

机构信息

State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China.

State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China.

出版信息

Colloids Surf B Biointerfaces. 2019 Sep 1;181:602-611. doi: 10.1016/j.colsurfb.2019.05.025. Epub 2019 May 12.

Abstract

The combination of chemotherapy and photothermal therapy is acknowledged as one of the most promising approaches in cancer treatment. Targeted delivery and controlled drug release are two important factors for combined chemo-photothermal therapy. In this study, a multifunctional nanoplatform based on gold nanorod (GNR) decorated with folate-conjugated poly(ethylene glycol)-b-poly(L-γ-glutamylhydrazine) (FEGGH) containing disulfide linker and dihydroxyphenyl groups was developed for targeted combined chemo-photothermal therapy of breast cancer. FEGGH was synthesized by ring-opening polymerization of γ-benzyl-l-glutamate-N-carboxyanhydride using folate/cystamine-heterobifunctionalized poly(ethylene glycol) as an initiator, following by hydrazinolysis and carbodiimide reactions. FEGGH was decorated onto GNR through Au-catechol bonds. Chemotherapeutic drug doxorubicin (DOX) was loaded onto the nanoplatform through pH-sensitive hydrazone linkage, obtaining final product FEGGH-GNR. The DOX-loaded nanoplatform displayed excellent photostability and reduction/pH dual-responsive drug release behavior. Cytological studies demonstrated the effective internalization of FEGGH-GNR into MCF-7 cells via folate-mediated endocytosis and additive therapeutic effect of combined photothermal-chemotherapy. These results indicate that our nanoplatform may be a promising strategy for targeted combined chemo-photothermal therapy of breast cancer.

摘要

化疗和光热疗法的联合被认为是癌症治疗中最有前途的方法之一。靶向递送和控制药物释放是联合化疗-光热治疗的两个重要因素。在这项研究中,开发了一种基于金纳米棒(GNR)的多功能纳米平台,该纳米平台用叶酸偶联的聚(乙二醇)-b-聚(L-γ-谷氨酰基肼)(FEGGH)进行修饰,其中包含二硫键连接物和二羟基苯基,用于乳腺癌的靶向联合化疗-光热治疗。FEGGH 通过使用叶酸/胱胺-杂双功能化聚(乙二醇)作为引发剂的γ-苄基-l-谷氨酸-N-羧酸酐开环聚合合成,随后进行肼解和碳二亚胺反应。FEGGH 通过 Au-儿茶酚键修饰到 GNR 上。通过 pH 敏感的腙键将化疗药物阿霉素(DOX)装载到纳米平台上,得到最终产物 FEGGH-GNR。负载 DOX 的纳米平台表现出优异的光稳定性和还原/pH 双重响应药物释放行为。细胞水平研究表明,FEGGH-GNR 通过叶酸介导的内吞作用有效内化进入 MCF-7 细胞,并具有联合光热化疗的附加治疗效果。这些结果表明,我们的纳米平台可能是用于乳腺癌靶向联合化疗-光热治疗的有前途的策略。

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