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Integrin-Targeted Nanoparticles for siRNA Delivery

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Integrin and Cell Adhesion Molecules

Part of the book series: Methods in Molecular Biology ((MIMB,volume 757))

Abstract

Integrins are heterodimeric membrane glycoproteins composed of noncovalently associated α and β subunits. Integrins support cell attachment and migration on the surrounding extracellular matrix as well as mediate cell–cell interaction in physiological and pathological settings. Constant recycling of integrins from the plasma membrane to the endosome makes integrins ideal receptors for the delivery of drugs to the cell cytoplasm. RNA interference (RNAi) has evolved not only as a powerful tool for studying gene expression and validating new drug targets, but also as a potential therapeutic intervention. However, the major challenge facing the translation of RNAi into clinical practice is the lack of efficient systemic delivery to specific cell types. Utilizing integrins as delivery target, we have recently devised a strategy to target leukocytes termed Integrin-targeted and stabilized NanoParticles (I-tsNPs) that entrap high RNAi payloads and deliver them in a leukocyte-specific manner to induce robust gene silencing.

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References

  1. de Fougerolles, A., Vornlocher, H. P., Maraganore, J., and Lieberman, J. (2007) Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug Discov. 6, 443–453.

    Article  PubMed  Google Scholar 

  2. Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., and Tuschl, T. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498.

    Article  PubMed  CAS  Google Scholar 

  3. Dykxhoorn, D. M., and Lieberman, J. (2005) The silent revolution: RNA interference as basic biology, research tool, and therapeutic. Annu. Rev. Med. 56, 401–423.

    Article  PubMed  CAS  Google Scholar 

  4. Dykxhoorn, D. M., and Lieberman, J. (2006) Running interference: prospects and obstacles to using small interfering RNAs as small molecule drugs. Annu. Rev. Biomed. Eng. 8, 377–402.

    Article  PubMed  CAS  Google Scholar 

  5. Peer, D., and Shimaoka, M. (2009) Systemic siRNA delivery to leukocyte-implicated ­diseases. Cell Cycle 8, 853–859.

    Article  PubMed  CAS  Google Scholar 

  6. Peer, D., Zhu, P., Carman, C. V., Lieberman, J., and Shimaoka, M. (2007) Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1. Proc. Natl. Acad. Sci. USA. 104, 4095–4100.

    Article  PubMed  CAS  Google Scholar 

  7. Peer, D., Park, E. J., Morishita, Y., Carman, C. V., and Shimaoka, M. (2008) Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science 319, 627–630.

    Article  PubMed  CAS  Google Scholar 

  8. Goffinet, C., and Keppler, O. T. (2006) Efficient nonviral gene delivery into primary lymphocytes from rats and mice. FASEB J. 20, 500–502.

    PubMed  CAS  Google Scholar 

  9. Bartlett, G. R. (1959) Colorimetric assay methods for free and phosphorylated glyceric acids. J. Biol. Chem. 234, 466–468.

    PubMed  CAS  Google Scholar 

  10. Peer, D., and Margalit, R. (2000) Physicochemical evaluation of a stability-driven approach to drug entrapment in regular and in surface-modified liposomes. Arch. Biochem. Biophys. 383, 185–190.

    Article  PubMed  CAS  Google Scholar 

  11. Olson, F., Hunt, C. A., Szoka, F. C., Vail, W. J., and Papahadjopoulos, D. (1979) Preparation of liposomes of defined size ­distribution by extrusion through polycarbonate membranes. Biochim. Biophys. Acta. 557, 9–23.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Prof. Motomu Shimaoka for his advice and encouragement and Dr. Yoshiyuki Morishita, and Dr. Charudharshini Srinivasan, for technical assistance. This work was supported by the European union – IRG (D.P.), the Alon Foundation (D.P.), and the Lewis Trust for Cancer Research (D.P.).

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Correspondence to Dan Peer .

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Ben-Arie, N., Kedmi, R., Peer, D. (2011). Integrin-Targeted Nanoparticles for siRNA Delivery. In: Shimaoka, M. (eds) Integrin and Cell Adhesion Molecules. Methods in Molecular Biology, vol 757. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-166-6_29

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  • DOI: https://doi.org/10.1007/978-1-61779-166-6_29

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-165-9

  • Online ISBN: 978-1-61779-166-6

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