Christian Büll (photo), PhD student in the research group of Prof. Gosse Adema, Dept. of Tumor Immunology, in close collaboration with the research teams of Dr. Thomas Boltje, Dept. of Molecular Chemistry, Prof. Carl Figdor, Dept. of Tumor Immunology and Dr. Jeanette Leusen, UMC Utrecht, published an article in the prestigious journal ACS Nano entitled: Targeted delivery of a sialic acid-blocking glycomimetic to cancer cells inhibits metastatic spread.
Cancer metastases, rather than primary tumors, are responsible for the largest percentage of cancer deaths. 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 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 nanoparticles coated with tumor-specific antibodies allowed targeted delivery of P-3Fax-Neu5Ac into melanoma cells, slow release, and long-term sialic acid blockade. Most importantly, 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. Targeting strategies to interfere with sialic acid-dependent processes are broadly applicable not only for different types of cancer but also in infection and inflammation.
C. Büll, T.J. Boltje, E.A.W. van Dinther, T. Peters, A.M. de Graaf, J.H.W. Leusen, M. Kreutz, C.G. Figdor, M.H. den Brok G.J. Adema. Targeted delivery of a sialic acid-blocking glycomimetic to cancer cells inhibits metastatic spread. 2015. DOI: 10.1021/nn5061964. ACS Nano
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