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Macromolecular Research

, Volume 21, Issue 11, pp 1201–1209 | Cite as

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

  • Hwa Jeong Lee
  • Ran Namgung
  • Won Jong Kim
  • Jae Il Kim
  • In-Kyu ParkEmail author
Article

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.

Keywords

cell-penetrating peptides tissue targeting gene delivery metastatic breast cancer microRNA-145 

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References

  1. (1).
    G. Romano, C. Pacilio, and A. Giordano, Stem Cells, 17, 191 (1999).CrossRefGoogle Scholar
  2. (2).
    C. T. Leong, C. K. Ong, S. K. Tay, and H. Huynh, Oncogene, 26, 870 (2007).CrossRefGoogle Scholar
  3. (3).
    L. Huang, Q. Ao, Q. Zhang, X. Yang, H. Xing, F. Li, G. Chen, J. Zhou, S. Wang, G. Xu, L. Meng, Y. Lu, and D. Ma, J. Cancer Res. Clin. Oncol., 136, 447 (2010).CrossRefGoogle Scholar
  4. (4).
    J. Soutschek, A. Akinc, B. Bramlage, K. Charisse, R. Constien, M. Donoghue, S. Elbashir, A. Geick, P. Hadwiger, J. Harborth, M. John, V. Kesavan, G. Lavine, R. K. Pandey, T. Racie, K. G. Rajeev, I. Rohl, I. Toudjarska, G. Wang, S. Wuschko, D. Bumcrot, V. Koteliansky, S. Limmer, M. Manoharan, and H. P. Vornlocher, Nature, 432, 173 (2004).CrossRefGoogle Scholar
  5. (5).
    A. L. Kasinski and F. J. Slack, Cancer Res., 72, 5576 (2012).CrossRefGoogle Scholar
  6. (6).
    J. B. Weidhaas, I. Babar, S. M. Nallur, P. Trang, S. Roush, M. Boehm, E. Gillespie, and F. J. Slack, Cancer Res., 67, 11111 (2007).CrossRefGoogle Scholar
  7. (7).
    X. Ye, Z. Liu, M. G. Hemida, and D. Yang, PLoS One, 6, e21215 (2011).CrossRefGoogle Scholar
  8. (8).
    E. Ylösmäki, S. Lavilla-Alonso, S. Jäämaa, M. Vähä-Koskela, T. af Hällström, A. Hemminki, J. Arola, H. Mäkisalo, and K. Saksela, PLoS One, 8, e54506 (2013).CrossRefGoogle Scholar
  9. (9).
    H. Zhang, J. Pu, T. Qi, M. Qi, C. Yang, S. Li, K. Huang, L. Zheng, and Q. Tong, Oncogene, doi:10.1038/onc.2012.574 (2012).Google Scholar
  10. (10).
    M. Sachdeva and Y. Y. Mo, Cancer Res., 70, 378 (2010).CrossRefGoogle Scholar
  11. (11).
    P. Dynoodt, R. Speeckaert, O. De Wever, I. Chevolet, L. Brochez, J. Lambert, and M. Van Gele, Int. J. Oncol., 42, 1443 (2013).Google Scholar
  12. (12).
    X. Wu, Z. Li, M. Yao, H. Wang, S. Qu, X. Chen, J. Li, Y. Sun, Y. Xu, and J. Gu, Acta Biochim. Biophys. Sin., 40, 217 (2008).CrossRefGoogle Scholar
  13. (13).
    C. F. LeMaistre, C. Meneghetti, L. Howes, and C. K. Osborne, Breast Cancer Res. Treat., 32, 97 (1994).CrossRefGoogle Scholar
  14. (14).
    D. G. Gilyazova, A. A. Rosenkranz, P. V. Gulak, V. G. Lunin, O. V. Sergienko, Y. V. Khramtsov, K. N. Timofeyev, M. A. Grin, A. F. Mironov, A. B. Rubin, G. P. Georgiev, and A. S. Sobolev, Cancer Res., 66, 10534 (2006).CrossRefGoogle Scholar
  15. (15).
    S. Gerbal-Chaloin, C. Gondeau, G. Aldrian-Herrada, F. Heitz, C. Gauthier-Rouviere, and G. Divita, Biol. Cell, 99, 223 (2007).CrossRefGoogle Scholar
  16. (16).
    C. Buerger and B. Groner, J. Cancer Res. Clin. Oncol., 129, 669 (2003).CrossRefGoogle Scholar
  17. (17).
    L. E. Yandek, A. Pokorny, A. Floren, K. Knoelke, U. Langel, and P. F. Almeida, Biophys. J., 92, 2434 (2007).CrossRefGoogle Scholar
  18. (18).
    J. Nguyen, X. Xie, M. Neu, R. Dumitrascu, R. Reul, J. Sitterberg, U. Bakowsky, R. Schermuly, L. Fink, T. Schmehl, T. Gessler, W. Seeger, and T. Kissel, J. Gene Med., 10, 1236 (2008).CrossRefGoogle Scholar
  19. (19).
    F. Salomone, F. Cardarelli, M. Di Luca, C. Boccardi, R. Nifosi, G. Bardi, L. Di Bari, M. Serresi, and F. Beltram, J. Control. Release, 163, 293 (2012).CrossRefGoogle Scholar
  20. (20).
    S. L. Fang, T. C. Fan, H. W. Fu, C. J. Chen, C. S. Hwang, T. J. Hung, L. Y. Lin, and M. D. Chang, PLoS One, 8, e57318 (2013).CrossRefGoogle Scholar
  21. (21).
    G. Ter-Avetisyan, G. Tunnemann, D. Nowak, M. Nitschke, A. Herrmann, M. Drab, and M. C. Cardoso, J. Biol. Chem., 284, 3370 (2009).CrossRefGoogle Scholar
  22. (22).
    P. Saalik, A. Niinep, J. Pae, M. Hansen, D. Lubenets, U. Langel, and M. Pooga, J. Control. Release, 153, 117 (2011).CrossRefGoogle Scholar
  23. (23).
    T. Takeuchi, M. Kosuge, A. Tadokoro, Y. Sugiura, M. Nishi, M. Kawata, N. Sakai, S. Matile, and S. Futaki, ACS Chem. Biol., 1, 299 (2006).CrossRefGoogle Scholar
  24. (24).
    M. Fotin-Mleczek, S. Welte, O. Mader, F. Duchardt, R. Fischer, H. Hufnagel, P. Scheurich, and R. Brock, J. Cell Sci., 118, 3339 (2005).CrossRefGoogle Scholar
  25. (25).
    M. Whitney, J. L. Crisp, E. S. Olson, T. A. Aguilera, L. A. Gross, L. G. Ellies, and R. Y. Tsien, J. Biol. Chem., 285, 22532 (2010).CrossRefGoogle Scholar
  26. (26).
    A. Chauhan, A. Tikoo, A. K. Kapur, and M. Singh, J. Control. Release, 117, 148 (2007).CrossRefGoogle Scholar
  27. (27).
    Y. Lee, H. Y. Nam, J. Kim, M. Lee, J. W Yockman, S. K. Shin, and S. W. Kim, Mol. Ther., 20, 1360 (2012).CrossRefGoogle Scholar
  28. (28).
    H. Bachtarzi, M. Stevenson, V. Subr, K. Ulbrich, L. W. Seymour, and K. D. Fisher, J. Control. Release, 150, 196 (2011).CrossRefGoogle Scholar
  29. (29).
    K. Anwer, B. G. Rhee, and S. K. Mendiratta, Crit. Rev. Ther. Drug Carrier Syst., 20, 249 (2003).CrossRefGoogle Scholar
  30. (30).
    R. Namgung, K. Singha, M. K. Yu, S. Jon, Y. S. Kim, Y. Ahn, I. K. Park, and W. J. Kim, Biomaterials, 31, 4204 (2010).CrossRefGoogle Scholar
  31. (31).
    S. M. Kwon, H. Y. Nam, T. Nam, K. Park, S. Lee, K. Kim, I. C. Kwon, J. Kim, D. Kang, J. H. Park, and S. Y. Jeong, J. Control. Release, 128, 89 (2008).CrossRefGoogle Scholar

Copyright information

© The Polymer Society of Korea and Springer Sciene+Business Media Dordrecht 2013

Authors and Affiliations

  • Hwa Jeong Lee
    • 1
  • Ran Namgung
    • 2
  • Won Jong Kim
    • 2
  • Jae Il Kim
    • 3
  • In-Kyu Park
    • 1
    Email author
  1. 1.Department of Biomedical Sciences and Center for Biomedical Human Resources (BK-21 Project)Chonnam National University Medical SchoolGwangjuKorea
  2. 2.Department of Chemistry, BK21 Program, Polymer Research InstitutePohang University of Science and TechnologyGyeongbukKorea
  3. 3.Department of Life SciencesGwangju Institute of Science and TechnologyGwangjuKorea

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