Chemically activatable viral capsid functionalized for cancer targeting

Chun Chieh Chen, Li Xing, Marie Stark, Tingwei Ou, Prasida Holla, Kai Xiao, Shizuo G. Kamita, Bruce D. Hammock, Kit Lam, R. Holland Cheng

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Aim: To design a theranostic capsule using the virus-like nanoparticle of the hepatitis E virus modified to display breast cancer cell targeting functional group (LXY30). Methods: Five surface-exposed residues were mutated to cysteine to allow conjugation to maleimide-linked chemical groups via thiol-selective linkages. Engineered virus-like nanoparticles were then covalently conjugated to a breast cancer recognized ligand, LXY30 and an amine-coupled near-infrared fluorescence dye. Results: LXY30-HEV VLP was checked for its binding and entry to a breast cancer cell line and for tumor targeting in vivo to breast cancer tissue in mice. The engineered virus-like nanoparticle not only targeted cancer cells, but also appeared immune silent to native hepatitis E virus antibodies due to epitope disruption at the antibody-binding site. Conclusion: These results demonstrate the production of a theranostic capsule suitable for cancer diagnostics and therapeutics based on surface modification of a highly stable virus-like nanoparticle.

Original languageEnglish (US)
Pages (from-to)377-390
Number of pages14
JournalNanomedicine
Volume11
Issue number4
DOIs
StatePublished - Feb 1 2016

Keywords

  • cycloaddition of targeting ligand
  • cysteine replacement
  • hepatitis E
  • multivalent ligand display
  • virus-like particle

ASJC Scopus subject areas

  • Materials Science(all)
  • Bioengineering
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Development

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  • Cite this

    Chen, C. C., Xing, L., Stark, M., Ou, T., Holla, P., Xiao, K., Kamita, S. G., Hammock, B. D., Lam, K., & Cheng, R. H. (2016). Chemically activatable viral capsid functionalized for cancer targeting. Nanomedicine, 11(4), 377-390. https://doi.org/10.2217/nnm.15.207