Inhibition of cancer-associated thrombosis with redox-sensitive paclitaxel/heparin-deoxycholic acid nanoparticles

Although heparin-based nanoparticles are widely used to treat cancer, the knowledge on the effect of heparin derivative and heparin-based nanoparticles on cancer-associated thrombosis is still lacking. To address this issue, the heparin derivatives including amphiphilic heparin-deoxycholic acid (DOCA) polymer with non-sensitive (Hep-DOCA) and redox-sensitive properties (Hep-ss-DOCA) are synthesized, and paclitaxel (PTX) is encapsulated in heparin-based micelles to fabricate nanoparticles. The chemical structure of synthesized polymer, the size, morphology and stability of nanoparticles and redox-sensitivity of nanoparticles are analyzed. And the effect of heparin-deoxycholic acid polymer and PTX loaded nanoparticles on cancer-associated thrombosis are investigated both in vitro and in vivo. It is found that redox-sensitive PTX/nanoparticles is effectively in reducing thrombosis for cancer mice. This result is mainly attributed to down-regulation for coagulation after apoptosis of cancer cell. This work not only clarifies the effect of heparin-based nanoparticles on blood hypercoagulation but provides basic principles to inhibit cancer-associated thrombosis.