Novel HER2 aptamer selectively delivers cytotoxic drug to HER2-positive breast cancer cells in vitro

• Published in: Journal of translational medicine 2012-07, Vol.10 (1), p.148-148, Article 148
• Main Authors: Liu, Zhe, Duan, Jin-Hong, Song, Yong-Mei, Ma, Jie, Wang, Feng-Dan, Lu, Xin, Yang, Xian-Da
• Format: Article
• Language: English
• Subjects: Albumin; Anthracyclines; Antigenic determinants; Antineoplastic Agents - administration & dosage; Aptamer; Aptamers, Nucleotide - administration & dosage; Base Sequence; Binding sites; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Cancer cells; Cancer therapies; Chemotherapy; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA Primers; Doxorubicin - administration & dosage; Drug delivery systems; Drug therapy; Drugs; Experiments; Female; Flow Cytometry; Genes, erbB-2; HER2; Humans; Ligands; Peptides; Proteins; SELEX Aptamer Technique; Studies; Tumor Cells, Cultured; Tumor targeted therapy; Vehicles
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-10-148

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