| Autor: |
Nestele JA; Department of Cardiology and Angiology, University of Tübingen, 72076 Tubingen, Germany., Rohlfing AK; Department of Cardiology and Angiology, University of Tübingen, 72076 Tubingen, Germany., Dicenta V; Department of Cardiology and Angiology, University of Tübingen, 72076 Tubingen, Germany., Bild A; Department of Cardiology and Angiology, University of Tübingen, 72076 Tubingen, Germany., Eißler D; Department of Cardiology and Angiology, University of Tübingen, 72076 Tubingen, Germany.; DFG Heisenberg Group Thrombocardiology, University of Tübingen, 72076 Tubingen, Germany., Emschermann F; Department of Cardiology and Angiology, University of Tübingen, 72076 Tubingen, Germany., Kremser M; Department of Cardiology and Angiology, University of Tübingen, 72076 Tubingen, Germany., Krutzke K; Institute for Applied Physics, University of Tübingen, 72076 Tubingen, Germany., Schäffer TE; Institute for Applied Physics, University of Tübingen, 72076 Tubingen, Germany., Borst O; Department of Cardiology and Angiology, University of Tübingen, 72076 Tubingen, Germany.; DFG Heisenberg Group Thrombocardiology, University of Tübingen, 72076 Tubingen, Germany., Levi M; Department of Biomedical Engineering, Technion, Israel Institute of Technology, Haifa 3200003, Israel., Korin N; Department of Biomedical Engineering, Technion, Israel Institute of Technology, Haifa 3200003, Israel., Gawaz MP; Department of Cardiology and Angiology, University of Tübingen, 72076 Tubingen, Germany. |
| Abstrakt: |
Traditional antithrombotic agents commonly share a therapy-limiting side effect, as they increase the overall systemic bleeding risk. A novel approach for targeted antithrombotic therapy is nanoparticles. In other therapeutic fields, nanoparticles have enabled site-specific delivery with low levels of toxicity and side effects. Here, we paired nanotechnology with an established dimeric glycoprotein VI-Fc (GPVI-Fc) and a GPVI-CD39 fusion protein, thereby combining site-specific delivery and new antithrombotic drugs. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles, NP-BSA, NP-GPVI and NP-GPVI-CD39 were characterized through electron microscopy, atomic force measurements and flow cytometry. Light transmission aggregometry enabled analysis of platelet aggregation. Thrombus formation was observed through flow chamber experiments. NP-GPVI and NP-GPVI-CD39 displayed a characteristic surface coating pattern. Fluorescence properties were identical amongst all samples. NP-GPVI and NP-GPVI-CD39 significantly impaired platelet aggregation. Thrombus formation was significantly impaired by NP-GPVI and was particularly impaired by NP-GPVI-CD39. The receptor-coated nanoparticles NP-GPVI and the bifunctional molecule NP-GPVI-CD39 demonstrated significant inhibition of in vitro thrombus formation. Consequently, the nanoparticle-mediated antithrombotic effect of GPVI-Fc, as well as GPVI-CD39, and an additive impact of CD39 was confirmed. In conclusion, NP-GPVI and NP-GPVI-CD39 may serve as a promising foundation for a novel therapeutic approach regarding targeted antithrombotic therapy. |
