Long-circulating 15 nm micelles based on amphiphilic 3-helix peptide-peg conjugates

He Dong, Nikhil Dube, Jessica Y. Shu, Jai Seo, Lisa M. Mahakian, Katherine W. Ferrara, Ting Xu

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Figure Persented: Generating stable, multifunctional organic nanocarriers will have a significant impact on drug formulation. However, it remains a significant challenge to generate organic nanocarriers with a long circulation half-life, effective tumor penetration, and efficient clearance of metabolites. We have advanced this goal by designing a new family of amphiphiles based on coiled-coil 3-helix bundle forming peptide-poly(ethylene glycol) conjugates. The amphiphiles self-assemble into monodisperse micellar nanoparticles, 15 nm in diameter. Using the 3-helix micelles, a drug loading of ∼8 wt % was obtained using doxorubicin and the micelles showed minimal cargo leakage after 12 h of incubation with serum proteins at 37 °C. In vivo pharmacokinetics studies using positron emission tomography showed a circulation half-life of 29.5 h and minimal accumulation in the liver and spleen. The demonstrated strategy, by incorporating unique protein tertiary structure in the headgroup of an amphiphile, opens new avenues to generate organic nanoparticles with tunable stability, ligand clustering, and controlled disassembly to meet current demands in nanomedicine.

Original languageEnglish (US)
Pages (from-to)5320-5329
Number of pages10
JournalACS Nano
Volume6
Issue number6
DOIs
StatePublished - Jun 26 2012

Keywords

  • 3-helix micelle
  • helix bundle
  • nanocarriers
  • peptide-polymer conjugate
  • stability

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Long-circulating 15 nm micelles based on amphiphilic 3-helix peptide-peg conjugates'. Together they form a unique fingerprint.

  • Cite this

    Dong, H., Dube, N., Shu, J. Y., Seo, J., Mahakian, L. M., Ferrara, K. W., & Xu, T. (2012). Long-circulating 15 nm micelles based on amphiphilic 3-helix peptide-peg conjugates. ACS Nano, 6(6), 5320-5329. https://doi.org/10.1021/nn301142r