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Structural plasticity of a transmembrane peptide allows self-assembly into biologically active nanoparticles

  1. Author:
    Tarasov, S. G.
    Gaponenko, V.
    Howard, O. M. Z.
    Chen, Y. H.
    Oppenheim, J. J.
    Dyba, M. A.
    Subramaniam, S.
    Lee, Y.
    Michejda, C.
    Tarasova, N. I.

  2. Author Address

    [Howard, OMZ; Chen, YH; Oppenheim, JJ; Tarasova, NI] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA [Tarasov, SG; Dyba, MA; Michejda, C] NCI, Struct Biophys Lab, Frederick, MD 21702 USA [Gaponenko, V; Lee, Y] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA [Dyba, MA] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA [Subramaniam, S] NCI, Cell Biol Lab, Bethesda, MD 20892 USA;Tarasova, NI (reprint author), NCI, Canc & Inflammat Program, POB B, Frederick, MD 21702 USA;Nadya.Tarasova@nih.gov
    1. Year: 2011
    2. Date: Jun
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 108
    2. 24
    3. Pages: 9798-9803
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. Abstract:

    Significant efforts have been devoted to the development of nanoparticular delivering systems targeting tumors. However, clinical application of nanoparticles is hampered by insufficient size homogeneity, difficulties in reproducible synthesis and manufacturing, frequent high uptake in the liver, systemic toxicity of the carriers (particularly for inorganic nanoparticles), and insufficient selectivity for tumor cells. We have found that properly modified synthetic analogs of transmembrane domains of membrane proteins can self-assemble into remarkably uniform spherical nanoparticles with innate biological activity. Self-assembly is driven by a structural transition of the peptide that adopts predominantly a beta-hairpin conformation in aqueous solutions, but folds into an alpha-helix upon spontaneous fusion of the nanoparticles with cell membrane. A 24-amino acid peptide corresponding to the second transmembrane helix of the CXCR4 forms self-assembled particles that inhibit CXCR4 function in vitro and hamper CXCR4-dependent tumor metastasis in vivo. Furthermore, such nanoparticles can encapsulate hydrophobic drugs, thus providing a delivery system with the potential for dual biological activity.

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External Sources

  1. View Full Text
  2. DOI: 10.1073/pnas.1014598108
  3. View record in Web of Science®
  4. WOS: 000291594000019

Library Notes

  1. Fiscal Year: FY2010-2011
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