'Multicopy multivalent' glycopolymer-stabilized gold nanoparticles as potential synthetic cancer vaccines

Alison L. Parry, Natasha A. Clemson, James Ellis, Stefan S. R. Bernhard, Benjamin G. Davis, Neil R. Cameron

Research output: Contribution to journalArticleResearchpeer-review

130 Citations (Scopus)

Abstract

Mucin-related carbohydrates are overexpressed on the surface of cancer cells, providing a disease-specific target for cancer immunotherapy. Here, we describe the design and construction of peptide-free multivalent glycosylated nanoscale constructs as potential synthetic cancer vaccines that generate significant titers of antibodies selective for aberrant mucin glycans. A polymerizable version of the Tn-antigen glycan was prepared and converted into well-defined glycopolymers by Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. The polymers were then conjugated to gold nanoparticles, yielding 'multicopy-multivalent' nanoscale glycoconjugates. Immunological studies indicated that these nanomaterials generated strong and long-lasting production of antibodies that are selective to the Tn-antigen glycan and cross-reactive toward mucin proteins displaying Tn. The results demonstrate proof-of-concept of a simple and modular approach toward synthetic anticancer vaccines based on multivalent glycosylated nanomaterials without the need for a typical vaccine protein component. 

Original languageEnglish
Pages (from-to)9362-9365
Number of pages4
JournalJournal of the American Chemical Society
Volume135
Issue number25
DOIs
Publication statusPublished - 13 Jun 2013
Externally publishedYes

Cite this

Parry, Alison L. ; Clemson, Natasha A. ; Ellis, James ; Bernhard, Stefan S. R. ; Davis, Benjamin G. ; Cameron, Neil R. / 'Multicopy multivalent' glycopolymer-stabilized gold nanoparticles as potential synthetic cancer vaccines. In: Journal of the American Chemical Society. 2013 ; Vol. 135, No. 25. pp. 9362-9365.
@article{f5ec066cbd3449bbaafbac1756366f49,
title = "'Multicopy multivalent' glycopolymer-stabilized gold nanoparticles as potential synthetic cancer vaccines",
abstract = "Mucin-related carbohydrates are overexpressed on the surface of cancer cells, providing a disease-specific target for cancer immunotherapy. Here, we describe the design and construction of peptide-free multivalent glycosylated nanoscale constructs as potential synthetic cancer vaccines that generate significant titers of antibodies selective for aberrant mucin glycans. A polymerizable version of the Tn-antigen glycan was prepared and converted into well-defined glycopolymers by Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. The polymers were then conjugated to gold nanoparticles, yielding 'multicopy-multivalent' nanoscale glycoconjugates. Immunological studies indicated that these nanomaterials generated strong and long-lasting production of antibodies that are selective to the Tn-antigen glycan and cross-reactive toward mucin proteins displaying Tn. The results demonstrate proof-of-concept of a simple and modular approach toward synthetic anticancer vaccines based on multivalent glycosylated nanomaterials without the need for a typical vaccine protein component. ",
author = "Parry, {Alison L.} and Clemson, {Natasha A.} and James Ellis and Bernhard, {Stefan S. R.} and Davis, {Benjamin G.} and Cameron, {Neil R.}",
year = "2013",
month = "6",
day = "13",
doi = "10.1021/ja4046857",
language = "English",
volume = "135",
pages = "9362--9365",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "ACS Publications",
number = "25",

}

'Multicopy multivalent' glycopolymer-stabilized gold nanoparticles as potential synthetic cancer vaccines. / Parry, Alison L.; Clemson, Natasha A.; Ellis, James; Bernhard, Stefan S. R.; Davis, Benjamin G.; Cameron, Neil R.

In: Journal of the American Chemical Society, Vol. 135, No. 25, 13.06.2013, p. 9362-9365.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 'Multicopy multivalent' glycopolymer-stabilized gold nanoparticles as potential synthetic cancer vaccines

AU - Parry, Alison L.

AU - Clemson, Natasha A.

AU - Ellis, James

AU - Bernhard, Stefan S. R.

AU - Davis, Benjamin G.

AU - Cameron, Neil R.

PY - 2013/6/13

Y1 - 2013/6/13

N2 - Mucin-related carbohydrates are overexpressed on the surface of cancer cells, providing a disease-specific target for cancer immunotherapy. Here, we describe the design and construction of peptide-free multivalent glycosylated nanoscale constructs as potential synthetic cancer vaccines that generate significant titers of antibodies selective for aberrant mucin glycans. A polymerizable version of the Tn-antigen glycan was prepared and converted into well-defined glycopolymers by Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. The polymers were then conjugated to gold nanoparticles, yielding 'multicopy-multivalent' nanoscale glycoconjugates. Immunological studies indicated that these nanomaterials generated strong and long-lasting production of antibodies that are selective to the Tn-antigen glycan and cross-reactive toward mucin proteins displaying Tn. The results demonstrate proof-of-concept of a simple and modular approach toward synthetic anticancer vaccines based on multivalent glycosylated nanomaterials without the need for a typical vaccine protein component. 

AB - Mucin-related carbohydrates are overexpressed on the surface of cancer cells, providing a disease-specific target for cancer immunotherapy. Here, we describe the design and construction of peptide-free multivalent glycosylated nanoscale constructs as potential synthetic cancer vaccines that generate significant titers of antibodies selective for aberrant mucin glycans. A polymerizable version of the Tn-antigen glycan was prepared and converted into well-defined glycopolymers by Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. The polymers were then conjugated to gold nanoparticles, yielding 'multicopy-multivalent' nanoscale glycoconjugates. Immunological studies indicated that these nanomaterials generated strong and long-lasting production of antibodies that are selective to the Tn-antigen glycan and cross-reactive toward mucin proteins displaying Tn. The results demonstrate proof-of-concept of a simple and modular approach toward synthetic anticancer vaccines based on multivalent glycosylated nanomaterials without the need for a typical vaccine protein component. 

UR - http://www.scopus.com/inward/record.url?scp=84879513677&partnerID=8YFLogxK

U2 - 10.1021/ja4046857

DO - 10.1021/ja4046857

M3 - Article

VL - 135

SP - 9362

EP - 9365

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 25

ER -