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一种用于靶向递送达铂药物的纳米抗体偶联 DNA 纳米平台。

A Nanobody-Conjugated DNA Nanoplatform for Targeted Platinum-Drug Delivery.

机构信息

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 11 BeiYiTiao, ZhongGuanCun, Beijing, 100190, China.

University of Chinese Academy of Sciences, Beijing, 100049, China.

出版信息

Angew Chem Int Ed Engl. 2019 Oct 1;58(40):14224-14228. doi: 10.1002/anie.201909345. Epub 2019 Aug 27.


DOI:10.1002/anie.201909345
PMID:31389144
Abstract

The targeted delivery of chemotherapeutic drugs is a major challenge in the clinical treatment of cancer. Herein, we constructed a multifunctional DNA nanoplatform as a versatile carrier of the highly potent platinum-based DNA intercalator, 56MESS. In our rational design, 56MESS was efficiently loaded into the double-bundle DNA tetrahedron through intercalation with the DNA duplex. With the integration of a nanobody that both targets and blocks epidermal growth factor receptor (EGFR), the DNA nanocarriers exhibit excellent selectivity for cells with elevated EGFR expression (a common biomarker related to tumor formation) and combined tumor therapy without obvious systemic toxicity. This DNA-based platinum-drug delivery system provides a promising strategy for the treatment of tumors.

摘要

化疗药物的靶向递送是癌症临床治疗的一大挑战。在此,我们构建了一种多功能 DNA 纳米平台,作为高效能基于铂的 DNA 嵌入剂 56MESS 的通用载体。在我们的合理设计中,56MESS 通过与 DNA 双链体的嵌入被有效地装载到双链 DNA 四面体中。通过整合既靶向又阻断表皮生长因子受体(EGFR)的纳米抗体,DNA 纳米载体对 EGFR 表达升高的细胞(与肿瘤形成相关的常见生物标志物)表现出优异的选择性,并具有联合肿瘤治疗作用,而没有明显的全身毒性。这种基于 DNA 的铂类药物递送系统为肿瘤治疗提供了一种很有前途的策略。

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