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In situ synthesis of core-shell carbon nanowires as a potent targeted anticoagulant

Mao, Ju-Yi, Lin, Fu-Yin, Chu, Han-Wei, Harroun, Scott G., Lai, Jui-Yang, Lin, Han-Jia, Huang, Chih-Ching
Journal of colloid and interface science 2019 v.552 pp. 583-596
ammonium sulfite, anticoagulants, binding capacity, biocompatibility, carbon, carbonization, catalysts, coagulation, cost effectiveness, dissociation, fucoidan, heat, hemolysis, hemorrhage, nanowires, sodium alginate, synthesis, temperature, thrombin, thrombosis, toxicity testing
We have developed a one-pot synthesis of bio-carbon nanowires from the natural product sodium alginate at low temperature, without using any catalyst, for anticoagulation applications. Sodium alginate is carbonized and sulfated/sulfonated in situ by solid state heating of a mixture of sodium alginate and ammonium sulfite. By regulating the heating temperature and the ratio of ammonium sulfite to sodium alginate, we modulated the degree of sulfation/sulfonation and carbonization, as well as the morphology of the carbon nanomaterials. The core-shell sulfated/sulfonated bio-carbon nanowires (CNWsAlg@SOx) made by the reaction of a mixture of ammonium sulfite and sodium alginate with a mass ratio of 5 (ammonium sulfite to sodium alginate) at 165 °C for 3 h, exhibit strong inhibition of thrombin activity due to their ultrahigh binding affinity towards it (dissociation constant (Kd) = 8.7 × 10−11 M). The possible formation mechanism of the carbon nanowires has been proposed. The thrombin-clotting time delay caused by CNWsAlg@SOx is ∼ 170 times longer than that caused by sodium alginate. Hemolysis and cytotoxicity assays demonstrated the high biocompatibility of CNWsAlg@SOx. Furthermore, the thromboelastography of whole-blood coagulation and rat-tail bleeding assays further reveal that CNWsAlg@SOx have a much stronger anticoagulation activity than sodium alginate and naturally sulfated polysaccharides (e.g., fucoidan). Our results suggest that the low-temperature prepared, cost-effective, and highly biocompatible CNWsAlg@SOx show great potential as an efficient anticoagulant for the prevention and treatment of diseases associated with thrombosis.