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Surface Functionalization of Hepatitis E Virus Nanoparticles Using Chemical Conjugation Methods

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Targeting vault nanoparticles to specific cell surface receptors.

Valerie A Kickhoefer¹, Muri Han, Sujna Raval-Fernandes

¹Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1737, USA.

|February 12, 2009

Summary

Engineered vault nanoparticles can be modified to target specific cancer cells. These recombinant particles offer a promising new platform for targeted drug delivery systems.

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Area of Science:

Biotechnology
Nanotechnology
Cell Biology

Background:

Vault particles are naturally occurring nanostructures found in eukaryotic cells.
Recombinant vault particles self-assemble from major vault protein (MVP) and can be engineered for specific functions.

Purpose of the Study:

To engineer recombinant vault particles for targeted delivery to specific cell types.
To investigate the display and function of C-terminal peptide tags on engineered vault particles.

Main Methods:

Engineered three different tags (epitope, IgG-binding peptide, EGF) onto the C-terminus of MVP.
Produced modified vault particles using a baculovirus expression system.
Assessed the binding of modified vaults to A431 epithelial cancer cells expressing EGFR.

Main Results:

C-terminal peptide extensions were successfully displayed on the exterior of recombinant vault particles.
EGF-modified vaults directly bound to EGFR on cancer cells.
IgG-binding peptide-modified vaults facilitated binding via an anti-EGFR antibody.

Conclusions:

Engineered vault particles can be specifically targeted to cancer cells expressing EGFR.
This targeted binding capability is a crucial step towards utilizing vault particles as drug delivery vehicles.