Low molecular weight heparin (LMWH) is the guideline-based drug for antithrombotic treatment of cancer patients, but further direct antitumor effects beyond are a matter of ongoing debate. Although therapeutically established for decades, LMWH has several drawbacks mainly associated with its structural heterogeneity and origin from animal sources. Aiming to overcome these limitations, a library of synthetic heparin mimetic polymers consisting of homo- and copolymers of sulfonated and carboxylated non-carbohydrate monomers has recently been synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. These heparin mimetics were investigated for their capacities to interfere with simulated steps of tumor cell metastasis. Among them, homo- and copolymers from sodium 4-styrenesulfonate (poly(SSS)) with acrylic acid (poly(SSS-<i>co</i>-AA)) with a MW between 5 and 50 kDa efficiently attenuated cancer cell-induced coagulation, and thus platelet activation and degranulation similar to, or even better than LMWH. Furthermore, independent of anticoagulant activities, these polymers affected other metastasis-relevant targets with impressive affinities, without possessing cell toxicities. Hence, they blocked heparanase enzymatic activity outmatching commercial heparins or a glycosidic drug candidate. Furthermore, these polymers bind P-selectin and the integrin VLA-4 similar to, or even better than heparin, indicated by a biosensor approach and thus blocked efficiently melanoma cell binding.<br/>Consequently, this approach highlights the prospects of synthetic heparin mimetics as promising non-toxic compounds in oncology to potentially substitute heparin as anticoagulant and to better understand the mode of action of heparin as an antimetastatic drug.

Use of synthetic heparin mimetics as a promising approach to inhibit tumor - Host cell interactions in terms of metastasis

ACS Fall 2021

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