期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 135, 期 25, 页码 9362-9365出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja4046857
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资金
- EPSRC [G0700080]
- MRC [G0700080]
- Royal Society Wolfson Merit Award
- Biotechnology and Biological Sciences Research Council [EGA17763, BB/E004350/1, BB/C510824/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/E000614/1, EP/D023335/1, GR/T26542/01, EP/G026688/1, EP/I500200/1, EP/D023343/1] Funding Source: researchfish
- Medical Research Council [G0700080] Funding Source: researchfish
- BBSRC [BB/E004350/1] Funding Source: UKRI
- EPSRC [EP/E000614/1, EP/G026688/1, EP/I500200/1] Funding Source: UKRI
- MRC [G0700080] Funding Source: UKRI
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.
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