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.
Keywords: bioconjugation; rod-shaped plant virus; virus-like particle, surface functionalization, click chemistry, protein engineering.