Biostable Aptamer Rings Conjugated for Targeting Two Biomarkers on Circulating Tumor Cells in Vivo with Great Precision

• DOI: 10.1021/acs.chemmater.7b03044
• Publication Date: 2017-12-07T16:54:50Z
• Authors: Haiyan Dong; Longyu Han; Zai-Sheng Wu; Ting Zhang; Jingjing Xie; Ji Ma; Jie Wang; Tao Li; Yu Gao; Jingwei Shao; Patrick J. Sinko; Lee Jia
• Keywords: 0301 basic medicine; 03 medical and health sciences

Cancer metastatic spread is life-threatening and caused by circulating tumor cells (CTCs) that are very difficult to precisely capture in vivo. Here we show that two aptamer rings targeting different CTC biomarker epitopes conjugated on dendrimers capture CTCs with enhanced precision even in the presence of 108 interfering cells, or blood cells, and in mice or patient samples when compared with their single aptamer counterparts. The aptamer-conjugate inhibited in vivo metastasis and demonstrated enhanced biostability by resisting biodegradation caused by the endogenous nucleases. The capture arms of the aptamer conjugates could simultaneously and specifically seize two biomarkers (EpCAM and Her2). The double seizure resulted in significant cell-cycle arrest, apoptosis, and growth inhibition of the captured CTCs. The aptamer-conjugate highly penetrated and accumulated in mouse tumors. This study provides the first conceptual evidence that two aptamer rings, inexpensive but bioequivalent to their antibodies...