The covalent attachment of water-soluble polymers to proteins and nanoparticles has become a well-established method for increasing circulation half-life and dampening antigenicity. Poly(ethylene glycol) (PEG) is the current standard for the development of protein-polymer therapeutics, but there have been relatively few advancements in the field. Furthermore, there have been reports of anti-PEG immune responses developing after repeat administrations. Glycopolymers represent interesting alternatives in this area that warrant exploration due to their mimicry of nature. Viruses and pathogenic organisms often evade the immune system through the display of carbohydrates that block protein-protein interactions and/or resemble naturally occurring sugars. Here, we describe the synthesis, characterization, and testing of two distinct protein-polymer architectures prepared by atom-transfer radical polymerization (ATRP) and conjugation to a virus-like particle (VLP) platform. The VLP-polymer conjugates were extensively characterized and their circulation half-lives and immunogenicity were evaluated. Both of the protein-polymer constructs displayed lower antigenicity and prolonged circulation half-lives relative to unmodified particles. These findings represent promising steps toward the development of VLPs as passive drug delivery platforms.

Trafficking and immunological studies of polymer-labeled virus-like particles

254th National Meeting (2017)

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