Evaluation of doxorubicin-loaded 3-helix micelles as nanocarriers

Nikhil Dube, Jessica Y. Shu, He Dong, Jai Seo, Elizabeth Ingham, Azadeh Kheirolomoom, Pin Yuan Chen, John Forsayeth, Krystof Bankiewicz, Katherine W. Ferrara, Ting Xu

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Designing stable drug nanocarriers, 10-30 nm in size, would have significant impact on their transport in circulation, tumor penetration, and therapeutic efficacy. In the present study, biological properties of 3-helix micelles loaded with 8 wt % doxorubicin (DOX), ∼15 nm in size, were characterized to validate their potential as a nanocarrier platform. DOX-loaded micelles exhibited high stability in terms of size and drug retention in concentrated protein environments similar to conditions after intravenous injections. DOX-loaded micelles were cytotoxic to PPC-1 and 4T1 cancer cells at levels comparable to free DOX. 3-Helix micelles can be disassembled by proteolytic degradation of peptide shell to enable drug release and clearance to minimize long-term accumulation. Local administration to normal rat striatum by convection enhanced delivery (CED) showed greater extent of drug distribution and reduced toxicity relative to free drug. Intravenous administration of DOX-loaded 3-helix micelles demonstrated improved tumor half-life and reduced toxicity to healthy tissues in comparison to free DOX. In vivo delivery of DOX-loaded 3-helix micelles through two different routes clearly indicates the potential of 3-helix micelles as safe and effective nanocarriers for cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)3697-3705
Number of pages9
JournalBiomacromolecules
Volume14
Issue number10
DOIs
StatePublished - Oct 14 2013

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Materials Chemistry
  • Polymers and Plastics
  • Medicine(all)

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    Dube, N., Shu, J. Y., Dong, H., Seo, J., Ingham, E., Kheirolomoom, A., Chen, P. Y., Forsayeth, J., Bankiewicz, K., Ferrara, K. W., & Xu, T. (2013). Evaluation of doxorubicin-loaded 3-helix micelles as nanocarriers. Biomacromolecules, 14(10), 3697-3705. https://doi.org/10.1021/bm4010518