Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery

• Published in: Journal of the American Chemical Society Vol. 136; no. 7; pp. 2731 - 2734
• Main Authors: Wang, RuoWen, Zhu, Guizhi, Mei, Lei, Xie, Yan, Ma, Haibin, Ye, Mao, Qing, Feng-Ling, Tan, Weihong
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19-02-2014
• Subjects: Amides - chemistry; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Aptamers, Nucleotide - chemistry; Automation; Communication; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; HCT116 Cells; Humans; Phosphoric Acids - chemistry; Photochemical Processes; Solid-Phase Synthesis Techniques
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja4117395

Aptamer–drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy.