Journal
ACS NANO
Volume 9, Issue 1, Pages 733-745Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn5061964
Keywords
sialic acids; glycomimetic; PLGA nanoparticles; cancer; metastasis
Categories
Funding
- Radboud University Medical Center
- Scientific Research (NWO) Rubicon program
- Dutch Cancer Society [2009-4402]
- ERC [PATHFINDER-269019]
- NWO
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Sialic acid sugars are overexpressed by cancer cells and contribute to the metastatic cascade at multiple levels. Therapeutic interference of sialic acids, however, has been difficult to pursue because of the absence of dedicated tools. Here we show that a rationally designed sialic acid-blocking glycomimetic (P-3F(ax)-Neu5Ac) successfully prevents cancer metastasis. Formulation of P-3F(ax)-Neu5Ac into poly(lactic-co-glycolic acid nanoparticles coated with antityrosinase-related protein-1 antibodies allowed targeted delivery of P-3F(ax)-Neu5Ac into melanoma cells, slow release, and long-term sialic acid blockade. Most importantly, intravenous injections of melanoma-targeting P-3F(ax)-Neu5Ac nanoparticles prevented metastasis formation in a murine lung metastasis model. These findings stress the importance of sialoglycans in cancer metastasis and advocate that sialic acid blockade using rationally designed glycomimetics targeted to cancer cells can effectively prevent cancer metastases. This targeting strategy to interfere with sialic acid-dependent processes is broadly applicable not only for different types of cancer but also in infection and inflammation.
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