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 language | English (US) |
|---|---|
| Pages (from-to) | 377-390 |
| Number of pages | 14 |
| Journal | Nanomedicine |
| Volume | 11 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 1 2016 |
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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
Cite this
Chemically activatable viral capsid functionalized for cancer targeting. / Chen, Chun Chieh; Xing, Li; Stark, Marie; Ou, Tingwei; Holla, Prasida; Xiao, Kai; Kamita, Shizuo G.; Hammock, Bruce D.; Lam, Kit; Cheng, R. Holland.
In: Nanomedicine, Vol. 11, No. 4, 01.02.2016, p. 377-390.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chemically activatable viral capsid functionalized for cancer targeting
AU - Chen, Chun Chieh
AU - Xing, Li
AU - Stark, Marie
AU - Ou, Tingwei
AU - Holla, Prasida
AU - Xiao, Kai
AU - Kamita, Shizuo G.
AU - Hammock, Bruce D.
AU - Lam, Kit
AU - Cheng, R. Holland
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - cycloaddition of targeting ligand
KW - cysteine replacement
KW - hepatitis E
KW - multivalent ligand display
KW - virus-like particle
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UR - http://www.scopus.com/inward/citedby.url?scp=84956927664&partnerID=8YFLogxK
U2 - 10.2217/nnm.15.207
DO - 10.2217/nnm.15.207
M3 - Article
C2 - 26786134
AN - SCOPUS:84956927664
VL - 11
SP - 377
EP - 390
JO - Nanomedicine
JF - Nanomedicine
SN - 1743-5889
IS - 4
ER -