Molecularly Engineer Triptolide with Aptamers for High Specifici-ty and Cytotoxicity for Triple-Negative Breast Cancer.

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.