Immunological Properties of Protein-Polymer Nanoparticles

Stephen N. Crooke, Jukuan Zheng, Mitra S. Ganewatta, Sophia M. Guldberg, Theresa M. Reineke, M.g. Finn

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The covalent attachment of polymers to the surface of proteins and nanoparticles has been widely employed in the development of biomedical platforms capable of delaying or diminishing immune surveillance. The most widely employed polymer for these applications has been poly(ethylene glycol) (PEG), yet recent evidence has suggested that other polymer architectures and compositions provide significantly better in vitro and in vivo properties of protein-polymer hybrid materials. Moreover, few direct comparisons of PEG to these polymers have been reported. Here we describe the assembly and characterization of a series of polymer conjugates of a representative immunogenic viruslike particle (VLP) using (poly(oligo(ethylene glycol) methacrylate), poly(methacrylamido glucopyranose), and PEG, and an investigation of their ability to shield the protein from antibody recognition as a function of polymer loading density, chain length, architecture, and conjugation site. Increasing chain length and loading density were both found to significantly diminish antibody recognition of the VLP conjugates; the conformation adopted by different polymer architectures was also found to greatly influence antibody recognition. A direct comparison of these conjugates to PEGylated VLPs in vivo showed that all formulations gave rise to similar antibody titers that were significantly diminished relative to unmodified particles. Interestingly, the quality of the antibody response was impacted by the properties of the conjugate, with differences in observed affinity and avidity suggesting a complex dependence on loading density, chain length, and architecture.

Original languageEnglish (US)
Pages (from-to)93-103
Number of pages11
JournalACS Applied Bio Materials
Volume2
Issue number1
DOIs
StatePublished - Jan 22 2019

Keywords

  • immune shielding
  • PEG
  • PMAG
  • POEGMA
  • protein-polymer conjugates
  • viruslike particles

How much support was provided by MRSEC?

  • Partial

Reporting period for MRSEC

  • Period 5

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