Molecularly Engineering Triptolide with Aptamers for High Specificity and Cytotoxicity for Triple-Negative Breast Cancer

• Published in: Journal of the American Chemical Society 2020-02, Vol.142 (6), p.2699-2703
• Main Authors: He, Jiaxuan, Peng, Tianhuan, Peng, Yongbo, Ai, Lili, Deng, Zhengyu, Wang, Xue-Qiang, Tan, Weihong
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Aptamers, Nucleotide - chemistry; Cell Line, Tumor; Cell Proliferation - drug effects; Diterpenes - chemistry; Diterpenes - pharmacology; Diterpenes - therapeutic use; Epoxy Compounds - chemistry; Epoxy Compounds - pharmacology; Epoxy Compounds - therapeutic use; Female; Humans; Mice; Phenanthrenes - chemistry; Phenanthrenes - pharmacology; Phenanthrenes - therapeutic use; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; Xenograft Model Antitumor Assays
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.9b10510

Triple-negative breast cancer (TNBC) lacks three important receptors, ER, PR, and HER2. It is more aggressive and more likely to relapse after treatment, thus has been identified as one of the most malignant breast cancer types. The development of efficient targeted TNBC therapy is an important research topic in TNBC treatment. We report the development of a new aptamer–drug conjugate (ApDC), AS1411–triptolide conjugate (ATC), as targeted therapy for the treatment of TNBC with high efficacy. The conjugate possesses excellent specificity and high cytotoxicity against the MDA-MB-231 cell line. The advantages of our newly invented ATC are further highlighted by its excellent in vivo anti-TNBC efficacy and negligible side effects toward healthy organs.