Novel Aptamer-Drug Conjugate for Targeted Therapy in Triple-Negative Breast Cancer.

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-07-20 DOI:10.1021/acs.jmedchem.5c00492

Feng Xu,Jingtong Xu,Feng Han,Ke Wang,Fulong Wang,Hanyang Yu,Xiaoxiang Guan

引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy lacking targeted therapeutic modalities. Aptamers are promising targeting agents with high specificity and affinity. In this study, we identified a chemically modified nucleic acid aptamer (AptT1) that specifically recognized and internalized into TNBC cells. Mechanistic studies revealed that ANXA2 was an essential protein in facilitating AptT1 internalization via clathrin-mediated endocytosis. Furthermore, we constructed an aptamer-drug conjugate (ApDC) to selectively deliver a cytotoxic agent (SN38) to TNBC cells and demonstrated significant efficacy and safety in a TNBC xenograft model. These findings suggest that AptT1-based ApDC holds great potential as an innovative targeted strategy for TNBC.

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新型适配体-药物偶联物靶向治疗三阴性乳腺癌。

三阴性乳腺癌（TNBC）是一种高度侵袭性的恶性肿瘤，缺乏靶向治疗方式。适体是一种具有高特异性和高亲和力的靶向药物。在这项研究中，我们鉴定了一种化学修饰的核酸适体（AptT1），可以特异性识别并内化到TNBC细胞中。机制研究表明，ANXA2是通过网格蛋白介导的内吞作用促进AptT1内化的必需蛋白。此外，我们构建了一个适体-药物偶联物（ApDC），选择性地将细胞毒性药物（SN38）递送到TNBC细胞，并在TNBC异种移植模型中证明了显著的有效性和安全性。这些发现表明，基于aptt1的ApDC作为TNBC的创新靶向策略具有巨大的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.