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

Journal of Translational Medicine

Xian-Da Yang³  Xin Lu¹  Feng-Dan Wang¹  Jie Ma²  Yong-Mei Song²  Jin-Hong Duan³  Zhe Liu³ 

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

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

Others  :  1205933
DOI  :  10.1186/1479-5876-10-148

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

【 摘 要 】

Background

Aptamer-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.

Methods

In 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.

Results

The selected

aptamer

was an 86-nucleotide DNA molecule that bound to an epitope peptide of HER2 with a K_d of 18.9 nM. The aptamer also bound to the extracellular domain (ECD) of HER2 protein

with a K

d

of 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.

Conclusions

The results suggest that the selected HER2 aptamer may have application potentials in targeted therapy against HER2-positive

breast cancer cells

.

【 授权许可】

   
2012 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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