Targeted Delivery of a Sialic Acid-Blocking Glycomimetic to Cancer Cells Inhibits Metastatic Spread

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 gl...

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Bibliographic Details
Published in:ACS nano 2015-01, Vol.9 (1), p.733-745
Main Authors: Büll, Christian, Boltje, Thomas Jan, van Dinther, Eric A. W, Peters, Timo, de Graaf, Annemarie M. A, Leusen, Jeanette H. W, Kreutz, Martin, Figdor, Carl G, den Brok, Martijn H, Adema, Gosse J
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antibodies - chemistry
Antibodies - immunology
Biomimetic Materials - chemistry
Biomimetic Materials - pharmacology
Blocking
Cancer
Cascades
Drug Carriers - chemistry
Female
Formations
Lactic Acid - chemistry
Lung Neoplasms - secondary
Melanoma, Experimental - pathology
Membrane Glycoproteins - immunology
Mice
N-Acetylneuraminic Acid - antagonists & inhibitors
Nanoparticles
Nanoparticles - chemistry
Nanostructure
Neoplasm Metastasis
Polyglycolic Acid - chemistry
Sialic Acids - chemistry
Sialic Acids - pharmacology
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Summary: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-3Fax-Neu5Ac) successfully prevents cancer metastasis. Formulation of P-3Fax-Neu5Ac into poly(lactic-co-glycolic acid nanoparticles coated with antityrosinase-related protein-1 antibodies allowed targeted delivery of P-3Fax-Neu5Ac into melanoma cells, slow release, and long-term sialic acid blockade. Most importantly, intravenous injections of melanoma-targeting P-3Fax-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.
ISSN:1936-0851
1936-086X
DOI:10.1021/nn5061964