Novel HER2 Aptamer Selectively Delivers Cytotoxic Drug to HER2-positive Breast Cancer Cells in Vitro

Journal of Translational Medicine

Research

Jie Ma¹  Yong-Mei Song¹  Xian-Da Yang²  Zhe Liu²  Jin-Hong Duan²  Feng-Dan Wang³  Xin Lu³ 

[1] Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100021, Beijing, China;Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 100005, Beijing, China;Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100073, Beijing, China;

关键词: Aptamer;    HER2;    Breast cancer;    Tumor targeted therapy;   

DOI  :  10.1186/1479-5876-10-148

 received in 2012-02-27, accepted in 2012-07-20,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAptamer-based tumor targeted drug delivery system is a promising approach that may increase the efficacy of chemotherapy and reduce the related toxicity. HER2 protein is an attractive target for tumor-specific drug delivery because of its overexpression in multiple malignancies, including breast, gastric, ovarian, and lung cancers.MethodsIn this paper, we developed a new HER2 aptamer (HB5) by using systematic evolution of ligands by exponential enrichment technology (SELEX) and exploited its role as a targeting ligand for delivering doxorubicin (Dox) to breast cancer cells in vitro.ResultsThe selected aptamer was an 86-nucleotide DNA molecule that bound to an epitope peptide of HER2 with a Kd of 18.9 nM. The aptamer also bound to the extracellular domain (ECD) of HER2 protein with a Kdof 316 nM , and had minimal cross reactivity to albumin or trypsin. In addition, the aptamer was found to preferentially bind to HER2-positive but not HER2-negative breast cancer cells. An aptamer-doxorubicin complex (Apt-Dox) was formulated by intercalating Dox into the DNA structure of HB5. The Apt-Dox complex could selectively deliver Dox to HER2-positive breast cancer cells while reducing the drug intake by HER2-negative cells in vitro. Moreover, Apt-Dox retained the cytotoxicity of Dox against HER2-positive breast cancer cells, but reduced the cytotoxicity to HER2-negative cells.ConclusionsThe results suggest that the selected HER2 aptamer may have application potentials in targeted therapy against HER2-positive breast cancer cells .

【 授权许可】

Unknown   
© Liu et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.