Targeting Vault Nanoparticles to Specific Cell Surface Receptors

Abstract

As a naturally occurring nanocapsule abundantly expressed in nearly all-eukaryotic cells, the barrel-shaped vault particle is perhaps an ideal structure to engineer for targeting to specific cell types. Recombinant vault particles self-assemble from 96 copies of the major vault protein (MVP), have dimensions of 72.5 × 41 nm, and have a hollow interior large enough to encapsulate hundreds of proteins. In this study, three different tags were engineered onto the C-terminus of MVP: an 11 amino acid epitope tag, a 33 amino acid IgG-binding peptide, and the 55 amino acid epidermal growth factor (EGF). These modified vaults were produced using a baculovirus expression system. Our studies demonstrate that recombinant vaults assembled from MVPs containing C-terminal peptide extensions, display these tags at the top and bottom of the vault on the outside of the particle, and can be used to specifically bind the modified vaults to epithelial cancer cells (A431) via the epidermal growth factor receptor (EGFR), either directly (EGF modified vaults) or as mediated by a monoclonal antibody (anti-EGFR) bound to recombinant vaults containing the IgG-binding peptide. The ability to target vaults to specific cells represents an essential advance towards using recombinant vaults as delivery vehicles.

Nanotechnology to augment immunotherapy for the treatment of glioblastoma multiforme

“…Therefore, they present as a potential delivery vehicle for various therapeutics. These nanoparticles can be functionalized to target specific markers on the surface of tumor cells [73]. They have already been shown to be a potential treatment for lung cancer when utilized synergistically with immunotherapeutics [74].…”

Smart-Drug Delivery and Target-Specific Therapy

“…Using this information, two different tumor cell-targeting approaches for vaults were developed (Kickhoefer et al, 2009). One approach was to fuse epidermal growth factor (EGF) to the C-terminus of MVP, generating vaults that were efficiently taken up by tumor cells lines overexpressing the EGF receptor.…”

Microscale methods to assemble mammalian cells into tissue-like structures

“…However, receptor-ligand interactions are transient in nature, determined by intrinsic binding and dissociation kinetics [86], which restricts their utility for stable coupling of material-cell surfaces [87]. However, multivalent binding of ligand-decorated materials with cell surface receptors can lead to stable cell surface binding [88,89] (Figure 3F).…”