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MC8 Peptide-Mediated Her-2 Receptor Targeting Based on PEI-β-CyD as Gene Delivery Vector

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Abstract

A novel vector with high gene delivery efficiency and special cell targeting ability was developed using a good strategy that utilized low molecular weight polyethylenimine (PEI; molecular weight, 600 KDa [PEI600]) cross-linked to β-cyclodextrin (β-CyD) via a facile synthetic route. Human epidermal growth factor receptor 2 (Her-2) are highly expressed in a variety of human cancer cells and are potential targets for cancer therapy. MC8 peptides, which have been proven to combine especially with Her-2 on cell membranes were coupled to PEI-β-CyD using N-succinimidyl-3-(2-pyridyldithio) propionate as a linker. The ratios of PEI600, β-CyD, and peptide were calculated based on proton integral values obtained from the 1H-NMR spectra of the resulting products. Electron microscope observations showed that MC8-PEI-β-CyD can efficiently condense plasmid DNA (pDNA) into nanoparticles of about 200 nm, and MTT assays suggested the decreased toxicity of the polymer. Experiments on gene delivery efficiency in vitro showed that MC8-PEI-β-CyD/pDNA polyplexes had significantly greater transgene activities than PEI-β-CyD/pDNA in the Skov3 and A549 cells, which positively expressed Her-2, whereas, no such effect was observed in the MCF-7 cells, which negatively expressed Her-2. Our current research indicated that the synthesized nonviral vector shows improved gene delivery efficiency and targeting specificity in Her-2 positive cells.

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References

  1. Li, D., Yu, H., Huang, H., Shen, F., Wu, X., Li, J., et al. (2007). FGF receptor-mediated gene delivery using ligands coupled to polyethylenimine. Journal of Biomaterials Applications, 22, 163–180.

    Article  CAS  Google Scholar 

  2. Morille, M., Passirani, C., Vonarbourg, A., Clavreul, A., & Benoit, J. P. (2008). Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials, 29, 3477–3496.

    Article  CAS  Google Scholar 

  3. Pack, D. W., Hoffman, A. S., Pun, S., & Stayton, P. S. (2005). Design and development of polymers for gene delivery. Nature Reviews, 4, 581–593.

    CAS  Google Scholar 

  4. Lee, M., & Kim, S. W. (2005). Polyethylene glycol-conjugated copolymers for plasmid DNA delivery. Pharmaceutical Research, 22, 1–10.

    Article  CAS  Google Scholar 

  5. Demeneix, B., Behr, J., Boussif, O., Zanta, M. A., Abdallah, B., & Remy, J. (1998). Gene transfer with lipospermines and polyethylenimines. Advanced Drug Delivery Reviews, 30, 85–95.

    Article  Google Scholar 

  6. Goyal, R., Tripathi, S. K., Tyagi, S., Ravi, R. K., Ansari, K. M., Shukla, Y., et al. (2011). Gellan gum blended PEI nanocomposites as gene delivery agents: evidences from in vitro and in vivo studies. European Journal of Pharmaleutics and Biopharmaceutics, 79, 3–14.

    Article  CAS  Google Scholar 

  7. Swami, A., Kurupati, R. K., Pathak, A., Singh, Y., Kumar, P., & Gupta, K. C. (2007). A unique and highly efficient non-viral DNA/siRNA delivery system based on PEI-bisepoxide nanoparticles. Biochemical and Biophysical Research Communications, 362, 835–841.

    Article  CAS  Google Scholar 

  8. Remant Bahadur, K. C., & Uludağ, H. (2011). A comparative evaluation of disulfide-linked and hydrophobically-modified PEI for plasmid delivery. Journal of Biomaterials Science, 22, 873–892.

    Article  CAS  Google Scholar 

  9. Chumakova, O. V., Liopo, A. V., Andreev, V. G., Cicenaite, I., Evers, B. M., Chakrabarty, S., et al. (2008). Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo. Cancer Letters, 261, 215–225.

    Article  CAS  Google Scholar 

  10. Wada, K., Arima, H., Tsutsumi, T., Chihara, Y., Hattori, K., Hirayama, F., et al. (2005). Improvement of gene delivery mediated by mannosylated dendrimer/alpha-cyclodextrin conjugates. Journal Control Release, 104, 397–413.

    Article  CAS  Google Scholar 

  11. Tang, G. P., Guo, H. Y., Alexis, F., Wang, X., Zeng, S., Lim, T. M., et al. (2006). Low molecular weight polyethylenimines linked by beta-cyclodextrin for gene transfer into the nervous system. The Journal of Gene Medicine, 8, 736–744.

    Article  CAS  Google Scholar 

  12. Chertok, B., David, A. E., & Yang, V. C. (2011). Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration. Biomaterias, 31, 6317–6324.

    Article  Google Scholar 

  13. Youn, J. I., Park, S. H., Jin, H. T., Lee, C. G., Seo, S. H., Song, M. Y., et al. (2008). Enhanced delivery efficiency of recombinant adenovirus into tumor and mesenchymal stem cells by a novel PTD. Cancer Gene Therapy, 15, 703–712.

    Article  CAS  Google Scholar 

  14. Rao, K. S., Reddy, M. K., Horning, J. L., & Labhasetwar, V. (2008). TAT-conjugated nanoparticles for the CNS delivery of anti-HIV drugs. Biomaterials, 29, 4429–4438.

    Article  CAS  Google Scholar 

  15. Schmidt, N., Mishra, A., Lai, G. H., & Wong, G. C. (2010). Arginine-rich cell-penetrating peptides. FEBS Letters, 584, 1806–183.

    Article  CAS  Google Scholar 

  16. Li, Z., Zhao, R., Wu, X., Sun, Y., Yao, M., Li, J., et al. (2005). Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics. The FASEB Journal, 19, 1978–1985.

    Article  CAS  Google Scholar 

  17. Mendonça, L. S., Firmino, F., Moreira, J. N., Pedrosode Lima, M. C., & Simões, S. (2010). Transferrin receptor-targeted liposomes encapsulating anti-BCR-ABL siRNA or as ODN for chronic myeloid leukemia treatment. Bioconjug Chemistry, 21, 157–168.

    Article  Google Scholar 

  18. Neu, M., Fischer, D., & Kissel, T. (2005). Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives. The Journal of Gene Medicine, 7, 992–1009.

    Article  CAS  Google Scholar 

  19. Fortune, J. A., Novobrantseva, T. I., & Klibanov, A. M. (2011). Highly effective gene transfection in vivo by alkylated polyethylenimine. Journal of Drug Delivery, 20, 40–58.

    Google Scholar 

  20. Houimel, M., Schneider, P., Terskikh, A., & Mach, J. P. (2001). Selection of peptides and synthesis of pentameric peptabody molecules reacting specifically with ErbB-2 receptor. International Journal of Cancer, 92, 748–755.

    Article  CAS  Google Scholar 

  21. Boussif, O., Lezoualc'h, F., Zanta, M. A., Mergny, M. D., Scherman, D., Demeneix, B., et al. (1995). A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proceedings of the National Academy of Sciences of the United States of America, 92, 7297–7301.

    Article  CAS  Google Scholar 

  22. Liu, G., Xie, J., Zhang, F., Wang, Z., Luo, K., Zhu, L., et al. (2011). N-Alkyl-PEI-functionalized iron oxide nanoclusters for efficient siRNA delivery. Small (Weinheim an der Bergstrasse, Germany), 7, 2742–2749.

    Article  CAS  Google Scholar 

  23. Bai, X., Miao, D., Li, J., Goltzman, D., & Karaplis, A. C. (2004). Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders. Endocrinology, 145, 5269–5279.

    Article  CAS  Google Scholar 

  24. Cai, L., Qiu, N., Li, X., Luo, K., Chen, X., Yang, L., et al. (2011). A novel truncated basic fibroblast growth factor fragment-conjugated poly (ethylene glycol)-cholesterol amphiphilic polymeric drug delivery system for targeting to the FGFR-overexpressing tumor cells. International Journal of Pharmaceutics, 408, 173–182.

    Article  CAS  Google Scholar 

  25. Slamon, D. J., Godolphin, W., Jones, L. A., Holt, J. A., Wong, S. G., Keith, D. E., et al. (1989). Studies of the HER-2/Neu proto-oncogene in human breast and ovarian cancer. Science, 244, 707–712.

    Article  CAS  Google Scholar 

  26. Liang, B., He, M. L., Xiao, Z. P., Li, Y., Chan, C. Y., Kung, H. F., et al. (2008). Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery. Biochemical and Biophysical Research Communications, 367, 874–880.

    Article  CAS  Google Scholar 

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We declare that there is no conflict of interest in this paper.

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi, 341000, China

    Wei Deng, Hefang Xiao & Xiangfu Zeng

  2. Center for Translational Medicine Research and Development, Shen Zhen Institute of Advanced Technology, Chinese Academy of Science, Shen Zhen, Guangdong, 518055, China

    Yiping Hu

  3. Shenzhen University Town, 1068 Xueyuan Avenue, Shenzhen, China

    Yiping Hu

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  1. Wei Deng
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  2. Hefang Xiao
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  3. Xiangfu Zeng
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  4. Yiping Hu
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Correspondence to Yiping Hu.

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Wei Deng and Hefang Xiao contributed equally as first authors.

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Deng, W., Xiao, H., Zeng, X. et al. MC8 Peptide-Mediated Her-2 Receptor Targeting Based on PEI-β-CyD as Gene Delivery Vector. Appl Biochem Biotechnol 169, 450–461 (2013). https://doi.org/10.1007/s12010-012-9959-2

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  • DOI: https://doi.org/10.1007/s12010-012-9959-2

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