Chemical conjugation of cowpea mosaic viruses with reactive HPMA-based polymers

J Biomater Sci Polym Ed. 2010;21(12):1669-85. doi: 10.1163/092050609X12547435571131. Epub 2010 Jun 9.

Abstract

N-(2-Hydroxypropyl)methacrylamide (HPMA) co-polymers containing disulfide and carbonyl thiazolidine-2-thione (TT) reactive groups in their side-chains (pHPMA-TT) were used as reductively removable chemical modification of the surface of cowpea mosaic viruses (CPMV). CPMV was used in this study as a model particle for viral gene delivery. The co-polymer reaction with CPMV surfaces carried out in aqueous solution was evaluated by monitoring the changes in the weight-average molecular weight and hydrodynamic size of the viruses using light scattering methods. The reaction conditions were optimized. The surface modification of CPMV with pHPMA-TT under selected conditions (concentrations of a coating polymer (c(p)) and NaCl) has not influenced the size distribution of the viral particles. The uncharged polymers bound to the viral surface via biodegradable S-S bonds can be fully removed by the exchange reaction with reductive dithiothreitol. To achieve optimal covering of viral surfaces, the positively charged reactive polymers (with or without biodegradable S-S bonds) should be applied at low concentrations (c(p)=0.1-0.5 mg/ml) and in presence of NaCl (0.15 M).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry
  • Biomimetics
  • Comovirus / chemistry*
  • Disulfides / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Intracellular Space / metabolism
  • Methacrylates / chemistry*
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Surface Properties
  • Thiazolidines / chemistry

Substances

  • Biocompatible Materials
  • Disulfides
  • Methacrylates
  • Polymers
  • Thiazolidines
  • 2-mercaptothiazoline
  • hydroxypropyl methacrylate