Nanoparticle-core virus-like particles for intracellular probing

ANYL 386

Bogdan Dragnea, dragnea@indiana.edu, Department of Chemistry, Indiana University, 800 E. Kirkwood Ave, Bloomington, IN 47405-7102
There is increased interest in the use of engineered virus capsids and protein cage structures as therapeutic and diagnostic vectors and imaging agents. The interest stems from the regular structural motif displayed by virus capsids and from the innate functional attributes acquired by viruses during evolution such as targeting and non-intrusive delivery of cargo into the cell. For example, main current challenges for nanoparticle delivery are limited life-time in biological fluids, efficient delivery across the cellular membrane, avoidance of the exocytotic pathways, and target specificity. Viruses have already overcome these challenges, but we still have to learn how to harvest their benefits. For such applications, it is vitally important to be able to control the interaction between the artificial cargo and the protein carrier (capsid). Much of the rules governing the assembly and stability of capsids incorporating artificial cores, and controlled disassembly are not yet determined. We have recently demonstrated that viral proteins can be self-assembled to form hybrid virus-like particles (VLPs) composed of a functionalized nanoparticle core surrounded by a symmetric protein cage. Such VLPs exhibit optical properties imparted by the encased nanoparticle (quantum dots or gold nanocrystals) and structural and functional properties of the native virus such as a symmetric, icosahedral capsid and pH-induced swelling. Moreover, we have shown that, functionalized artificial cores composed of quantum dots or gold nanoparticles can efficiently direct in vitro virus assembly of nanoparticles. The functionalized cores can thus mimic and potentially improve upon the natural properties of biological macromolecules for assembly. Control of the assembly kinetics and of the VLP structures is thus achievable by adjusting the surface properties of the functionalized nanoparticle core. We discuss here studies that have set the stage to elucidate the basic rules for nanoparticle core VLP assembly, with potential applications.