Nearly half a century ago it was discovered that the overexpression of sialic acid sugars on the surface of cancer cells aided their ability to metastasize, and thus, sialic acid sugars became a potential therapeutic target. Recent advances in glycobiology and cancer research have helped to elucidate the exact roles sialic acid sugars play in the metastatic cascade. There is increasing evidence that sialic acids on the surface of cells are involved in and drive numerous distinct processes during cancer metastasis including escape from apoptosis, enhanced migration and tissue invasion, metastasis and resistance to chemotherapies. Interference with sialic acids on cancer cells could thus be of crucial importance in preventing cancer metastasis as multiple steps of the metastatic cascade could be targeted at the same time.
Building on these recent advances, a team of researchers led by Christian Büll at the Radboud Institute for Molecular Life Sciences, tested the efficacy of the global sialyltransferase inhibitor developed by Rillahan et al., P-3Fax-Neu5Ac. Their results, published in ACS Nano, show that P-3Fax-Neu5Ac successfully prevents cancer metastasis both in vitro and in vivo. Furthermore, by encasing P-3Fax-Neu5Ac in polylactic-co-glycolic acid nanoparticles the researchers were able to achieve targeted delivery of the inhibitor into meleanoma cells, slow relsease, 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.
The researchers believe this combined glycobiological and nanotechnological strategy to block sialic acid sugar expression in specific target cells will be broadly applicable to interfere with sialic acid-dependent processes in cancer as well as infection and inflammation. Moving forward, the team hopes to continue to unravel exactly how sialic acid blockade prevents metastasis and which of the steps in the metastasis process are most dependent on sialic acids.