Surface Functionalization of Rod-Shaped Viral Particles for Biomedical Applications

Abstract

While synthetic nanoparticles play a very important role in modern medicine, concerns regarding toxicity, sustainability, stability, and dispersity are drawing increasing attention to naturally derived alternatives. Rod-shaped plant viruses and virus-like particles (VLPs) are biological nanoparticles with powerful advantages such as biocompatibility, tunable size and aspect ratio, monodispersity, and multivalency. These properties facilitate controlled biodistribution and tissue targeting for powerful applications in medicine. Ongoing research efforts focus on functionalizing or otherwise engineering these structures for a myriad of applications, including vaccines, imaging, and drug delivery. These include chemical and biological strategies for conjugation to small molecule chemical dyes, drugs, metals, polymers, peptides, proteins, carbohydrates, and nucleic acids. Many strategies are available and vary greatly in efficiency, modularity, selectivity, and simplicity. This review provides a comprehensive summary of VLP functionalization approaches while highlighting biomedically relevant examples. Limitations of current strategies and opportunities for further advancement will also be discussed.

Isopeptide Bonding In Planta Allows Functionalization of Elongated Flexuous Proteinaceous Viral Nanoparticles, including Non-Viable Constructs by Other Means

“…Direct fusion of peptides or proteins via genetic fusion has long been used because it is a simple, effective, and selective method for functionalizing VLPs [ 4 ]. As in the case of GFP and VIP, the protein of interest is fused to a CP domain projected towards the exterior of the VLP.…”

“…Since its creation, the SpyTag/SpyCatcher approach has been used in several nanotechnological applications based on protein covalent coupling [ 18 , 31 , 32 ]. One of these applications is VNP functionalization, a field where this technology has been recently implemented with promising results [ 4 ]. In this study, we show how the SpyTag/SpyCatcher approach is a successful technique for TuMV VLPs’ functionalization as it allowed us to coat the VLPs with VIP after several unsuccessful attempts via genetic fusion and chemical conjugation [ 28 ].…”

“…In comparison with spherical viruses, elongated ones with a helical symmetry can represent a better choice in some instances, as their number of subunits per particle is much larger. Among these, tobacco mosaic virus (TMV) and potato virus X (PVX) have been widely used [ 4 ]. In our own work, we have a long track record in the development of VNPs from turnip mosaic virus (TuMV) for multiple nanobiotechnological applications [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

“…One solution to get round this problem is the partial functionalization of the VNPs, where their self-assembly is possible because there is a certain percentage of non-functionalized CPs [ 17 ]. Other options to avoid this problem are the addition of linkers between the capsid protein and the protein of interest or the deletion of some amino acids of the capsid protein to allow the fusion of larger peptides [ 4 ].…”

Multifunctional plant virus nanoparticles: An emerging strategy for therapy of cancer

“…The genome fuses desirable surface ligands to the coat protein and alters the surface components of PVNPs (Wen & Steinmetz, 2016). These unique properties of PVNPs, along with nanoengineering, can be used for various applications, including vaccines, imaging, and drug delivery (Vaidya & Solomon, 2022). Different nanoengineering strategies have been approved for the fabrication of multifunctional PVNP formulations, including encapsulation techniques (self‐assembly, infusion), bioconjugation chemistries, mineralization, and combination strategies.…”