(804g) Engineering Virus-Based Nanoparticles As Adjustable Platforms for High-Density Site-Directed Decoration

Nanoparticle technologies become increasingly valuable as demand for their applicable technologies escalates in fields such as nanosensing, imaging, drug and therapeutic delivery, biocatalysis, and electronics. A fundamental difficulty of nanotechnology is controlling the traits of synthetic nanoparticles, such as monodispersity, assembly, stability, size, and morphology. One compelling group of candidates that may address these fundamental challenges is that of viruses. Viruses derive portions of their structures from peptide-based complexes. These complexes form nanoparticles that are often monodispere, self-assembling, symmetric and stable under general physiological conditions. Virus-based nanoparticles (VNPs) may be engineered to be noninfectious and innocuous while maintaining desirable traits. Engineering VNPs for useful applications typically requires chemical modifications and ligations. Standard conjugation techniques target residue side-chains and peptide termini, but remain limited by native-residue availability and lack of site-directed control of conjugation. Fortuitously, recent expansion of the peptide code has allowed for the site-directed addition of noncanonical amino acids that contain bioorthogonal reactive moieties as side chains. By marrying the VNPs with noncanonical amino acid incorporation, we have been able to circumspectly engineer VNPs as tunable platforms for ligand conjugation. Specifically, we have demonstrated the site-directed high-density decoration of Qβ bacteriophage-based VNPs with fluorescent probes and polyethylene glycols. Conjugation sites were designed for both external and internal decoration and the characteristics of each type were observed. Imminent applications of these particles will be in areas of bioimaging and single-particle tracking with promising future applications such as targeted drug delivery, biocatalysis, and nanometric biosensing.