Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 126, Issue -, Pages 612-619Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2018.11.255
Keywords
Glycopolymer; Heparin mimic; Anti-metastasis; Tumor cell adhesion
Funding
- National Natural Science Foundation of China [21574059, 31700708, 21506112]
- Natural Science Foundation of Jiangsu Province [BK20170181]
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Numerous studies have proved that heparin, a sub-group of glycosaminoglycan, possesses great potential as anti metastasis agent. However, the native strong anti-coagulant activity which causes serious side effects, such as bleeding, has limited its clinical applications for safety concern. To overcome this problem, we synthesized a panel of novel glycopolymers that mimic heparin structure with substantially reduced anti-coagulant activity by a simple grafted-on strategy. The influence of molecular weight & distribution, substituting degree and sulfonic density on cytotoxicity were determined by systematic MU analysis to select the candidates with highly bio-compatibility. Among these glycopolymers, a sulfated poly-2-aminoethyl methacrylate grafted with heparin disaccharide (abbreviated as SGPHD) has shown potent efficacy in inhibition of heparanase activity and micro vascular endothelial cell proliferation in vitro. Further experiments demonstrated that SGPHD inhibited B16 murine melanoma cell migration, invasion and adhesion to platelets or microvascular endothelial cells, thus, presented as a possible anti-metastatic agent by providing a whole course protection during tumor metastasis. The results will have significant impacts for the further rational design of glycopolymer medicine. (C) 2018 Published by Elsevier B.V.
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