Many clinical conditions such as intoxications, systemic infections or autoimmune diseases are caused by substances that are distributed in the blood circulation. The specific removal of these disease-causing factors from a patient’s blood would be in many cases the most direct way of cure. But current blood purification methods are not applicable to specifically and efficiently remove larger biomolecules such as bacterial toxins or antibodies directly from a patient’s blood. After years of research we have found a solution to that problem: Magnetic blood purification.
Our first development candidate focuses on Sepsis, a blood spread infection with so far only very limited treatment options.
HOW IT WORKS
With our breakthrough approach called Magnetic Blood Purification we can selectively remove harmful substances from blood of a patient based on highly magnetic nanoparticles. These tiny non-toxic nanomagnets are chemically equipped with specific binding agents against harmful disease-causing substances. The nanomagnets are administered to an extracorporeal blood circuit which is connected to the patient’s blood stream. There they selectively bind to the harmful compounds. Before the blood flows back to the patient the magnets are removed along with the target substances by a highly efficient separator. The nanomagnets themselves stay always outside of the body.
The scientific background of the project has been published in numerous academic journals. A prototype device has been built and tested in animal experiments whereby feasibility and efficacy of the removal of specific substances (endotoxin, cytokines, drugs, heavy metals) were proven (Ref. 1-4). In addition, the biocompatibility (e.g., blood compatibility, inflammatory response, cytotoxicity) and the long-term effects of injected nanomagnets over one year in mice were evaluated (Ref. 5-9). All preclinical tests indicated good biocompatibility and therapy tolerability.
(1) Herrmann, I. K.; Grass, R. N.; Mazunin, D.; Stark, W. J. Synthesis and Covalent Surface Functionalization of Nonoxidic Iron Core−Shell Nanomagnets. Chem. Mater. 2009, 21 (14), 3275–3281. http://pubs.acs.org/doi/abs/10.1021/cm900785u
(2) Herrmann, I. K.; Bernabei, R. E.; Urner, M.; Grass, R. N.; Beck-Schimmer, B.; Stark, W. J. Device for Continuous Extracorporeal Blood Purification Using Target-Specific Metal Nanomagnets. Nephrol. Dial. Transplant. 2011, 26 (9), 2948–2954.
(3) Herrmann, I. K.; Schlegel, A.; Graf, R.; Schumacher, C. M.; Senn, N.; Hasler, M.; Gschwind, S.; Hirt, A.-M.; Günther, D.; Clavien, P.-A.; et al. Nanomagnet-Based Removal of Lead and Digoxin from Living Rats. Nanoscale 2013, 5 (18), 8718–8723.
(4) Herrmann, I. K.; Urner, M.; Graf, S.; Schumacher, C. M.; Roth-Z’graggen, B.; Hasler, M.; Stark, W. J.; Beck-Schimmer, B. Endotoxin Removal by Magnetic Separation-Based Blood Purification. Adv. Healthc. Mater. 2013, 2 (6), 829–835.
(5) Herrmann, I. K.; Urner, M.; Koehler, F. M.; Hasler, M.; Roth-Z’Graggen, B.; Grass, R. N.; Ziegler, U.; Beck-Schimmer, B.; Stark, W. J. Blood Purification Using Functionalized Core/Shell Nanomagnets. Small 2010, 6 (13), 1388–1392.
(6) Herrmann, I. K.; Urner, M.; Hasler, M.; Roth-Z’Graggen, B.; Aemisegger, C.; Baulig, W.; Athanassiou, E. K.; Regenass, S.; Stark, W. J.; Beck-Schimmer, B. Iron Core/shell Nanoparticles as Magnetic Drug Carriers: Possible Interactions with the Vascular Compartment. Nanomed. 2011, 6 (7), 1199–1213.
(7) Bircher, L.; Theusinger, O. M.; Locher, S.; Eugster, P.; Roth-Z’graggen, B.; Schumacher, C. M.; Studt, J.-D.; Stark, W. J.; Beck-Schimmer, B.; Herrmann, I. K. Characterization of Carbon-Coated Magnetic Nanoparticles Using Clinical Blood Coagulation Assays: Effect of PEG-Functionalization and Comparison to Silica Nanoparticles. J. Mater. Chem. B 2014, 2 (24), 3753–3758.
(8) Jacobson, M.; Roth Z’graggen, B.; Graber, S. M.; Schumacher, C. M.; Stark, W. J.; Dumrese, C.; Mateos, J. M.; Aemisegger, C.; Ziegler, U.; Urner, M.; et al. Uptake of Ferromagnetic Carbon-Encapsulated Metal Nanoparticles in Endothelial Cells: Influence of Shear Stress and Endothelial Activation. Nanomed. 2015.
(9) Herrmann, I. K.; Beck-Schimmer, B.; Schumacher, C. M.; Gschwind, S.; Kaech, A.; Ziegler, U.; Clavien, P.-A.; Günther, D.; Stark, W. J.; Graf, R.; et al. In Vivo Risk Evaluation of Carbon-Coated Iron Carbide Nanoparticles Based on Short- and Long-Term Exposure Scenarios. Nanomed. 2016, 11 (7), 783–796.
(10) Bougas, L.; Langenegger, L. D.; Mora, C. A.; Zeltner, M.; Stark, W. J.; Wickenbrock, A.; Blanchard, J. W.; Budker, D. Nondestructive In-Line Sub-Picomolar Detection of Magnetic Nanoparticles in Flowing Complex Fluids. Sci. Rep. 2018, 8 (1), 3491.