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Vaults Engineered for Hydrophobic Drug Delivery

  1. Daniel C. Buehler1,
  2. Daniel B. Toso2,
  3. Valerie A. Kickhoefer1,
  4. Z. Hong Zhou2,3,
  5. Leonard H. Rome1,3,*

Article first published online: 20 APR 2011

DOI: 10.1002/smll.201002274

Issue

Small

Small

Special Issue: Nanotechnology with Soft Matter

Volume 7, Issue 10, pages 1432–1439, May 23, 2011

Additional Information

How to Cite

Buehler, D. C., Toso, D. B., Kickhoefer, V. A., Zhou, Z. H. and Rome, L. H. (2011), Vaults Engineered for Hydrophobic Drug Delivery. Small, 7: 1432–1439. doi: 10.1002/smll.201002274

Author Information

  1. 1

    Department of Biological Chemistry, David Geffen School of Medicine, 615 Charles E. Young Dr. South, University of California, Los Angeles, CA 90095, USA

  2. 2

    Department of Microbiology, Immunology & Molecular Genetics, and Biomedical Engineering Program, 609 Charles E. Young Dr. South, University of California, Los Angeles, California 90095, USA

  3. 3

    California Nanosystems Institute, University of California, Los Angeles, California 90095, USA

*Department of Biological Chemistry, David Geffen School of Medicine, 615 Charles E. Young Dr. South, University of California, Los Angeles, CA 90095, USA.

Publication History

  1. Issue published online: 19 MAY 2011
  2. Article first published online: 20 APR 2011
  3. Manuscript Received: 16 DEC 2010

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Keywords:

  • vaults;
  • nanoparticles;
  • nanodisk;
  • all-trans retinoic acid;
  • drug delivery

Abstract

The vault nanoparticle is one of the largest known ribonucleoprotein complexes in the sub-100 nm range. Highly conserved and almost ubiquitously expressed in eukaryotes, vaults form a large nanocapsule with a barrel-shaped morphology surrounding a large hollow interior. These properties make vaults an ideal candidate for development into a drug delivery vehicle. In this study, the first example of using vaults towards this goal is reported. Recombinant vaults are engineered to encapsulate the highly insoluble and toxic hydrophobic compound all-trans retinoic acid (ATRA) using a vault-binding lipoprotein complex that forms a lipid bilayer nanodisk. These recombinant vaults offer protection to the encapsulated ATRA from external elements. Furthermore, a cryo-electron tomography (cryo-ET) reconstruction shows the vault-binding lipoprotein complex sequestered within the vault lumen. Finally, these ATRA-loaded vaults show enhanced cytotoxicity against the hepatocellular carcinoma cell line HepG2. The ability to package therapeutic compounds into the vault is an important achievement toward their development into a viable and versatile platform for drug delivery.

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