Construction of Bispecific Aptamer–Drug Conjugate by a Hybrid Chemical and Biological Approach
Yang Sun, Fei Gao, Yang Cai, Yingying Li, Cheng Jin, Sitao Xie, Cheng Lv, Ding Ding, Da Han, Juan Li, Ruowen Wang, Weihong Tan
Abstract
Bispecific aptamer–drug conjugates (BsApDC) may improve the efficacy of drugs by enhancing cellular internalization and targeted delivery. Nevertheless, the synthesis of single-molecular BsApDC has not yet been reported, and it could be thwarted by synthetic challenges. Herein we report a general approach to synthesize a BsApDC hybridized chemical and biological method. Primers incorporated with 5-Fluorouracil (5-FU), 10-Hydroxycamptothecin, and Maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl auristatin E(vcMMAE) were prepared by chemical synthesis, which were converted to corresponding ApDCs efficiently by enzymatic reaction. Biological studies revealed that BsApDC binds with target cells with enhanced internalization and better inhibitory activity, demonstrating the potential of BsApDCs for targeted tumor therapy.