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三阴性乳腺癌治疗用类特洛伊木马肽药物偶联物的设计与构建。

Trojan-Like Peptide Drug Conjugate Design and Construction for Application in Treatment of Triple-Negative Breast Cancer.

机构信息

Department of Breast and Thyroid Surgery, Zibo Central Hospital, Zibo, Shandong, 255036, P. R. China.

Departments of the Golden Chamber, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, P. R. China.

出版信息

J Biomed Nanotechnol. 2021 Aug 1;17(8):1554-1563. doi: 10.1166/jbn.2021.3104.

Abstract

Clinical treatment of triple negative breast cancer (TNBC) is very poor for lack of effective treatment combination selection. Protein C receptor (PROCR) is a novel cancer stem marker in TNBC patients tumor tissues. Developed based on peptide BP10 with affinity to PROCR as a targeting element, constructing a peptide drug conjugate of BP10 covalently coupling doxorubicin with disulfide bonds. This study demonstrated that the constructed BP10-DOX can selectively target Triplenegative breast cancer cells expressing PROCR and controlled release of DOX in response to the GSH environment. Moreover, BP10-DOX improves the therapeutic efficiency on MDA-MB-231 cells . Further evidence obtained from xenograft experiments revealed that administration of BP10-DOX enhanced the antitumor efficacy. This study developed a promising chemotherapy strategy for TNBC.

摘要

三阴性乳腺癌(TNBC)的临床治疗效果很差,因为缺乏有效的治疗组合选择。蛋白 C 受体(PROCR)是 TNBC 患者肿瘤组织中的一种新型癌症干细胞标志物。本研究以与 PROCR 具有亲和力的肽 BP10 为靶向元件,构建了一种将 DOX 通过二硫键共价偶联到 BP10 上的肽药物偶联物。该研究表明,构建的 BP10-DOX 可以选择性地靶向表达 PROCR 的三阴性乳腺癌细胞,并响应 GSH 环境实现 DOX 的控制释放。此外,BP10-DOX 提高了对 MDA-MB-231 细胞的治疗效率。进一步的异种移植实验结果表明,BP10-DOX 的给药增强了抗肿瘤疗效。本研究为 TNBC 开发了一种有前途的化疗策略。

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