Chemically activatable viral capsid functionalized for cancer targeting. (February 2016)

• Record Type: Journal Article
• Authors: Chen, Chun-Chieh; Xing, Li; Stark, Marie; Ou, Tingwei; Holla, Prasida; Xiao, Kai; Kamita, Shizuo G; Hammock, Bruce D; Lam, Kit; Cheng, R Holland
• Is Part Of: Nanomedicine. Volume 11:Number 4(2016)
• Page Start: 377
• Page End: 390
• Publication Date: 2016-02
• Subjects: cycloaddition of targeting ligand -- cysteine replacement -- hepatitis E -- multivalent ligand display -- virus-like particle; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.15.207
• Languages: English
• ISSNs: 1743-5889

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.