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用于增强局部癌症治疗的铂(IV)前药骨架胶束和载有二氯乙酸的纳米纤维

Pt(iv) prodrug-backboned micelle and DCA loaded nanofibers for enhanced local cancer treatment.

作者信息

Zhang Zhiyun, Wu Yanjuan, Kuang Gaizhen, Liu Shi, Zhou Dongfang, Chen Xuesi, Jing Xiabin, Huang Yubin

机构信息

State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.

出版信息

J Mater Chem B. 2017 Mar 21;5(11):2115-2125. doi: 10.1039/c7tb00178a. Epub 2017 Feb 27.

Abstract

Drug-loaded nanocarriers, especially polymeric micelles, have attracted much attention in recent years, but their application is still limited due to their systemic toxicity and unsatisfactory tumor delivery efficiency through intravenous administration. In this study, we demonstrated an implantable prodrug micelle/small drug molecule co-loaded nanofiber strategy for enhanced local cancer treatment. A reduction-responsive Pt(iv) prodrug-backboned micelle, as a prodrug of bioactive Pt(ii), and DCA were co-electrospun into poly(vinyl alcohol) (PVA) nanofibers. The prepared Pt(iv) prodrug-backboned micelle/DCA fibers exerted a synergistic effect on cancer cells. In contrast to systemic administration of chemotherapeutic agents, this implantable device exhibited enhanced anti-cancer efficacy with lower systemic toxicity against advanced cervical cancer in vivo. This work provides a facile, efficient and safe prospect of using a prodrug micelle and small molecular drug co-loaded electrospun device for localized and advanced cancer therapy.

摘要

载药纳米载体,尤其是聚合物胶束,近年来备受关注,但其应用仍受到限制,因为它们具有全身毒性,且通过静脉给药的肿瘤递送效率不尽人意。在本研究中,我们展示了一种用于增强局部癌症治疗的可植入前药胶束/小分子药物共负载纳米纤维策略。一种还原响应型以铂(IV)前药为主链的胶束,作为生物活性铂(II)的前药,与二氯乙酸(DCA)共电纺到聚乙烯醇(PVA)纳米纤维中。制备的以铂(IV)前药为主链的胶束/DCA纤维对癌细胞发挥了协同作用。与全身给药化疗药物相比,这种可植入装置在体内对晚期宫颈癌表现出增强的抗癌疗效,且全身毒性更低。这项工作为使用前药胶束和小分子药物共负载电纺装置进行局部和晚期癌症治疗提供了一种简便、高效且安全的前景。

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