title: Novel HER2 aptamer selectively delivers cytotoxic drug to HER2-positive breast cancer cells in vitro.
abstract: 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 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.
  
  
  CONCLUSIONS
  The results suggest that the selected HER2 aptamer may have application potentials in targeted therapy against HER2-positive breast cancer cells.
authors: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors: Zhe
authors: Z
authors: Liu
authors: Jin-Hong
authors: JH
authors: Duan
authors: Yong-Mei
authors: YM
authors: Song
authors: Jie
authors: J
authors: Ma
authors: Feng-Dan
authors: FD
authors: Wang
authors: Xin
authors: X
authors: Lu
authors: Xian-Da
authors: XD
authors: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D052157:Aptamers, Nucleotide / Q000008:administration & dosage*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017931:DNA Primers; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D018734:Genes, erbB-2; D006801:Humans; D052156:SELEX Aptamer Technique; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D017931:DNA Primers; D004317:Doxorubicin