鈥楳ulticopy Multivalent鈥?Glycopolymer-Stabilized Gold Nanoparticles as Potential Synthetic Cancer Vaccines

详细信息    查看全文

• 作者：Alison L. Parry ; Natasha A. Clemson ; James Ellis ; Stefan S. R. Bernhard ; Benjamin G. Davis ; Neil R. Cameron
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：June 26, 2013
• 年：2013
• 卷：135
• 期：25
• 页码：9362-9365
• 全文大小：229K
• 年卷期：v.135,no.25(June 26, 2013)
• ISSN：1520-5126

文摘

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鈥揊ragmentation chain Transfer (RAFT) polymerization. The polymers were then conjugated to gold nanoparticles, yielding 鈥榤ulticopy-multivalent鈥?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.