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Targeted delivery of microRNA-145 to metastatic breast cancer by peptide conjugated branched PEI gene carrier

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Abstract

Development of a targeted polymeric gene delivery system is essential for reducing the non-specific uptake and toxicity of the gene carriers. In this study, we have tested the specificity of the cell penetrating peptide (DS 4-3), screened by phage display technique, towards metastatic breast cancer cells. This peptide has shown specificity towards metastatic breast cancer cells, which was confirmed through endocytosis inhibition study. Furthermore, the DS 4-3 peptide was conjugated to bPEI, to deliver the therapeutic miR-145. Tumor suppressor miR-145 inhibited tumor cell growth, and significantly suppressed cell invasion. The DS 4-3 peptide conjugated branched PEI (DSbPEI)/pLuc nanoparticles showed increased transfection in malignant murine breast cancer cells at the neutral surface charge (N/P molar ratio of 3), compared to scramble peptide conjugated bPEI/pLuc nanoparticles, without causing any cytotoxicity. This specific increase in transfection with DS-bPEI/pLuc nanoparticles was not found in the cancer cells that originated from different tissue, such as HeLa cervical cancer cells, or in the normal cells, such as NIH-3T3 murine fibroblast cells. Thus, the specific transfection of miR-145 in metastatic breast cancer cells mediated by DS-bPEI resulted in enhanced reduction in proliferation.

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Authors and Affiliations

  1. Department of Biomedical Sciences and Center for Biomedical Human Resources (BK-21 Project), Chonnam National University Medical School, Gwangju, 501-746, Korea

    Hwa Jeong Lee & In-Kyu Park

  2. Department of Chemistry, BK21 Program, Polymer Research Institute, Pohang University of Science and Technology, Gyeongbuk, 790-784, Korea

    Ran Namgung & Won Jong Kim

  3. Department of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea

    Jae Il Kim

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  1. Hwa Jeong Lee
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  2. Ran Namgung
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  3. Won Jong Kim
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  4. Jae Il Kim
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  5. In-Kyu Park
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Correspondence to In-Kyu Park.

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Lee, H.J., Namgung, R., Kim, W.J. et al. Targeted delivery of microRNA-145 to metastatic breast cancer by peptide conjugated branched PEI gene carrier. Macromol. Res. 21, 1201–1209 (2013). https://doi.org/10.1007/s13233-013-1161-z

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  • DOI: https://doi.org/10.1007/s13233-013-1161-z

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