Multivalent display of active ingredients on proteinaceous, virus-based nanoparticles (VNPs) offer advantages in medicine and agriculture. However, the degree of modification remains constrained by the solubility of the resulting VNP-ligand fusion. In particular, chemical fusions combining hydrophobic ligands and hydrophilic nanoparticles are challenging and prone to aggregation due to significant differences in solubility. Given the benefits of hydrophilic nanoparticle platforms for multivalent ligand display and targeted delivery, combined with the utility of hydrophobic drugs, peptides and contrast agents, this is an issue that must be addressed to realize the full potential of nanoparticles. We report two polymer preincubation strategies that employ a Pluronic F127 polymer scaffold to prevent aggregation of VNPs conjugated to a library of 11 hydrophobic ligands: (1) a VNP-polymer precoat (COAT) and (2) a combination of ligand formulation and VNP-polymer precoat (FORMCOAT). The broad applicability of these modified fusion strategies was highlighted by testing compatibility with several types of bioconjugation chemistry: NHS ester-amine coupling, copper(I)-catalyzed azide-alkyne cycloaddition (click chemistry), and maleimide-thiol coupling. Both COAT and FORMCOAT strategies yielded VNP conjugates with enhanced stability and monodispersity compared to that of conventional approaches. Formulation with F127 offers an avenue to improve the translational potential of VNP-conjugates whose applications in bioimaging, drug delivery, and vaccination can positively impact human and agricultural health.

Pluronic F127 preincubation approach to enhance bioconjugation of active ingredients to virus nanoparticles

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.