Virus-Based Nanoparticles as Versatile Nanomachines

Abstract

Nanoscale engineering is revolutionizing the way we prevent, detect, and treat diseases. Viruses have played a special role in these developments because they can function as prefabricated nanoscaffolds that have unique properties and are easily modified. The interiors of virus particles can encapsulate and protect sensitive compounds, while the exteriors can be altered to display large and small molecules in precisely defined arrays. These properties of viruses, along with their innate biocompatibility, have led to their development as actively targeted drug delivery systems that expand on and improve current pharmaceutical options. Viruses are naturally immunogenic, and antigens displayed on their surface have been used to create vaccines against pathogens and to break self-tolerance to initiate an immune response to dysfunctional proteins. Densely and specifically aligned imaging agents on viruses have allowed for high-resolution and noninvasive visualization tools to detect and treat diseases earlier than previously possible. These and future applications of viruses have created an exciting new field within the disciplines of both nanotechnology and medicine.

Keywords: drug delivery; imaging; nanotechnology; vaccines; viruses.

Figure 1

Structures of a selection of plant, bacteriophage, and animal viruses that have been used as virus-based nanoparticles. Structural data for icosahedral viruses were obtained from http://viperdb.scripps.edu/, and structural data for TMV were obtained from http://www.rcsb.org; images were produced using Chimera software (6). For PVX and M13, schematic representations of the virus particles are shown.

Figure 2

Generalized modification strategies to develop functionalized virus-based nanoparticles.

Figure 3

Frequently used virus-based nanoparticle amino acid bioconjugation schemes. Abbreviations: EDC, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; THPTA, tris(3-hydroxypropyltriazolylmethyl)amine.

Figure 3

Frequently used virus-based nanoparticle amino acid bioconjugation schemes. Abbreviations: EDC, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; THPTA, tris(3-hydroxypropyltriazolylmethyl)amine.

Figure 4

Fundamentals of tissue- or disease-targeted virus-based nanoparticles (VNPs). Targeting ligands are presented on the exterior of the VNP to facilitate active cell-specific surface binding and/or receptor-mediated endocytosis. Additional unique factors, such as the enhanced permeability and retention (EPR) effect in tumor masses or VNP shape, can further aid in passive localization.

Figure 5

Immune response activation by virus-based nanoparticles. Homogeneous or heterogeneous epitopes displayed on the surface of virus-based nanoparticles are taken up by antigen-presenting cell types and initiate activation of the humoral immune response, the cellular immune response, or both.