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Novel HER2 Aptamer Selectively Delivers Cytotoxic Drug to HER2-positive Breast Cancer Cells in Vitro.
- Source :
- Journal of Translational Medicine; 2012, Vol. 10 Issue 1, p148-157, 10p, 6 Charts
- Publication Year :
- 2012
-
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 K&<subscript>d</subscript> of 18.9 nM. The aptamer also bound to the extracellular domain (ECD) of HER2 protein with a K&<subscript>d</subscript> 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- APTAMERS
ANTINEOPLASTIC agents
LUNG cancer
DOXORUBICIN
TRYPSIN
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 10
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 83372948
- Full Text :
- https://doi.org/10.1186/1479-5876-10-148