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Molecularly Engineer Triptolide with Aptamers for High Specifici-ty and Cytotoxicity for Triple-Negative Breast Cancer
Journal of the American Chemical Society ( IF 15.0 ) Pub Date : 2020-01-07 , DOI: 10.1021/jacs.9b10510
Jiaxuan He 1 , Tianhuan Peng 1 , Yongbo Peng 1 , Lili Ai 1 , Zhengyu Deng 1 , Xue-Qiang Wang 1 , Weihong Tan 1, 2, 3, 4
Affiliation  

Triple-negative breast cancer (TNBC) lacks three important recep-tors (ER, PR, and HER2), and thus has been identified as one of the most malignant cancer types. The development of efficient tar-geted TNBC therapy has been considered as an important research topic in TNBC treatment. We report the development of a new ap-tamer-drug conjugate (ApDC), AS1411-triptolide conjugate (ATC), as targeted therapy for the treatment of TNBC with high efficacy. The coupling of triptolide with aptamer conferred it with excellent specificity and significantly increased cytotoxicity against the MDA-MB-231 cell line. The advantages of our newly invented ApDC were further highlighted by its excellent in vivo anti-TNBC efficacy, and negligible side effects towards healthy organs. Breast cancer is the most frequently diagnosed cancer among women in global. Immunohistochemical (IHC) indicates that breast cancer can be divided into three distinct groups based on the expression of three important receptors, estrogen receptor (ER), progesterone receptor (PR), and Erb-B2 Receptor Tyrosine Kinase 2 (HER2). Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express ER, PR, and HER2.1 Studies have shown it accounts for about 15-20% of all breast cancer cases.2 TNBC is much easier to spread to other healthy organs and more likely to relapse after treatment than the other breast cancer types, it thus has been considered to be the most malignant subtype of breast cancer.3 Currently, the treatment of TNBC usually relies on a combination of surgery, radiation therapy, and chemotherapy. It is of interest that TNBC tumors respond well to chemotherapy compared with other subtypes, however, the lack of ER, PR, and HER2 makes it more difficult to apply commonly used targeted cancer therapy approach-es such as endocrine therapy. It is thus particularly complicated to find the optimal chemotherapy for TBNC patients.4, 5 The develop-ment of novel yet practical chemotherapies thus become an urgent task to do, and would be greatly appreciated.

中文翻译:

分子工程雷公藤内酯与适体对三阴性乳腺癌具有高特异性和细胞毒性

三阴性乳腺癌(TNBC)缺乏三种重要的受体(ER、PR和HER2),因此被确定为恶性程度最高的癌症类型之一。开发有效的靶向 TNBC 疗法已被认为是 TNBC 治疗的重要研究课题。我们报告了一种新的适体-调和药物偶联物 (ApDC)、AS1411-雷公藤内酯偶联物 (ATC) 的开发,作为治疗 TNBC 的高效靶向疗法。雷公藤内酯与适体的偶联赋予其优异的特异性并显着增加对 MDA-MB-231 细胞系的细胞毒性。我们新发明的 ApDC 的优势进一步体现在其出色的体内抗 TNBC 功效和对健康器官可忽略不计的副作用。乳腺癌是全球女性中最常被诊断出的癌症。免疫组织化学 (IHC) 表明,根据三种重要受体、雌激素受体 (ER)、孕激素受体 (PR) 和 Erb-B2 受体酪氨酸激酶 2 (HER2) 的表达,乳腺癌可分为三个不同的组。三阴性乳腺癌 (TNBC) 是指任何不表达 ER、PR 和 HER2.1 的乳腺癌。研究表明,它约占所有乳腺癌病例的 15-20%。2 TNBC 更容易传播到其他健康器官,治疗后比其他乳腺癌类型更容易复发,因此被认为是乳腺癌最恶性的亚型。 3 目前,TNBC 的治疗通常依赖于手术、放射治疗、和化疗。有趣的是,与其他亚型相比,TNBC 肿瘤对化疗反应良好,然而,ER、PR 和 HER2 的缺乏使得应用常用的靶向癌症治疗方法(例如内分泌治疗)变得更加困难。因此,为 TBNC 患者寻找最佳化疗方案特别复杂。4, 5 因此,开发新颖而实用的化疗方案成为一项紧迫的任务,将不胜感激。
更新日期:2020-01-07
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