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Metal Nanomagnets for Medicine - Towards Single Cell Surgery

English title Metal Nanomagnets for Medicine - Towards Single Cell Surgery
Applicant Beck Schimmer Beatrice
Number 131268
Funding scheme NRP 64 Opportunities and Risks of Nanomaterials
Research institution Institut für Anästhesiologie Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Immunology, Immunopathology
Start/End 01.01.2011 - 30.11.2015
Approved amount 724'976.00
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Keywords (9)

carbon coated nanomagnets; life cycle; endothelial and hepatic inflammation; blood purification; Nanomagnets; Interaction with vascular compartment; Kupfer cells; hepatocytes; blood coagulation

Lay Summary (English)

Lead
Lay summary
Laysummary

Lead
Therapeutic applications and potential health risks of carbon protected magnetic metal nanoparticles (NPs) will be elucidated, focusing on efficiency of magnetically guiding NPs as well as elimination of toxic substances from the body. Compatibility in the vascular compartment will be tested as well as interaction of NPs with hepatic cells.???

Background
Carbon coated nanomagnets benefit from their uniquely high mobility, the exceptionally high specific surface area and the corresponding large capacity for reliable linking of functional groups, making them extremely effective drug carriers. The magneto-responsive properties allow control and targeting through magnetic gradient fields. Current problems associated with the use of magnetic microparticles are their low binding capacity, or a bad response to magnetic fields, particularly for oxide-based materials. Carbon coated metal NPs contribute to overcoming these drawbacks as their highly magnetic metal core allows rapid movement, yet their high specific surface area (10 - 10'000 times larger then microparticles) allows sufficient capacity to ligand binding.

Aim
Potentials and possible harms within the life cycle of carbon coated magnetic NPs will be assessed in this grant application. Regarding chances, magnetic NPs will be evaluated focusing on the possibility of magnetically guiding drugs to a desired region in the human body (e.g. bringing chemotherapeutics to a tumor). In a second scenario, using magnetic metal NPs, target molecule isolation in a detoxification procedure in situations such as drug overdose or misbalance in inflammatory mediators will be evaluated. As the knowledge on human exposure of engineered metal NPs is still very limited - in contrast, microparticles are under extended investigation - a detailed risk assessment is a prerequisite for a future therapeutic application. Therefore, key points of the life cycle of magnetic metal NPs will be evaluated (exposure of vascular compartment) and the liver (possible accumulation). The character of the interaction of magnetic metal NPs with endothelial, blood and hepatic cells will be assessed and possible inflammation reactions and/or toxicity will be determined. Additionally, bio-interaction during therapeutic application in the blood stream will be investigated regarding blood coagulation.

Significance
This project thereby lays the groundwork to bringing this promising new technology from bench to bedside involving basic researchers, clinicians and industrial partners.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
In vivo risk evaluation of carbon-coated iron carbide nanoparticles based on short- and long-term exposure scenarios
Herrmann Inge K, Beck-Schimmer B, Schumacher Christoph M, Gschwind Sabrina, Kaech Andres, Ziegler Urs, Clavien Pierre-Alain, Günther Detlef, Stark Wendelin J, Graf Rolf, Schlegel Andrea A (2016), In vivo risk evaluation of carbon-coated iron carbide nanoparticles based on short- and long-term exposure scenarios, in Nanomedicine, 11, 783-796.
Uptake of ferromagnetic carbon-encapsulated metal nanoparticles in endothelial cells: influence of shear stress and endothelial activation
Salamin (Jacobson) Melanie (2016), Uptake of ferromagnetic carbon-encapsulated metal nanoparticles in endothelial cells: influence of shear stress and endothelial activation, Doctoral thesis (MD, Faculty of Medicine) see original publication, University of Zurich.
Magnetic separation-based blood purification: a promising new approach for the removal of disease-causing compounds?
Herrmann Ing, Schlegel Andrea, Graf Rolf, Stark Wendelin, Beck-Schimmer Beatrice (2015), Magnetic separation-based blood purification: a promising new approach for the removal of disease-causing compounds?, in J Nanobiotechnology, 13, 49.
Uptake of ferromagnetic carbon-encapsulated metal nanoparticles in endothelial cells: influence of shear stress and endothelial activation
Jacobson Melanie, Roth Z'graggen Birgit, Graber Sereina, Schumacher Christoph M, Stark Wendelin, Dumrese Claudia, Mateos Jose, Aemisegger Caroline, Ziegler Urs, Urner Martin, Herrmann Inge, Beck-Schimmer Beatrice (2015), Uptake of ferromagnetic carbon-encapsulated metal nanoparticles in endothelial cells: influence of shear stress and endothelial activation, in Nanomedicine, 10, 3537-3546.
Visualizing the surface functionalization-dependent uptake of magnetic nanoparticles into phagocytic cells using confocal laser scanning reflectance microscopy
Peters Judith (2015), Visualizing the surface functionalization-dependent uptake of magnetic nanoparticles into phagocytic cells using confocal laser scanning reflectance microscopy, Doctoral thesis (MD; Faculty of Medicine), University of Zurich.
Carbon-coated magnetic nanoparticles: Interaction with the human blood coagulation system
Locher Silvan (2014), Carbon-coated magnetic nanoparticles: Interaction with the human blood coagulation system, Master thesis (Faculty of Medicine), University of Zurich.
Characterization of carbon-coated magnetic nanoparticles using clinical blood coagulation assays: Effect of PEG-functionalization and comparison to silica nanoparticles
Bircher Lukas, Theusinger Oliver, Locher Silvan, Eugster Philipp, Roth-Z'graggen Birgit, Schumacher Christoph, Studt Jan-Dirk, Stark Wendelin, Beck-Schimmer Beatrice, Herrmann Inge (2014), Characterization of carbon-coated magnetic nanoparticles using clinical blood coagulation assays: Effect of PEG-functionalization and comparison to silica nanoparticles, in J Mater Chem B, 2, 3753-3758.
Nanomagnet-based removal of lead and digoxin from living rats
Herrmann Inge K., Schlegel Andrea A, Graf Rolf, Schumacher Christoph M, Senn Nico, Hasler Melanie, Gschwind Sabrina, Hirt Ann-Marie, Günther Detleff, Clavien Pierre-Alain, Stark Wendelin J, Beck-Schimmer Beatrice (2013), Nanomagnet-based removal of lead and digoxin from living rats, in Nanoscale, 5(18), 8718-8723.
Quantitative Recovery of Magnetic Nanoparticles from Flowing Blood: Trace Analysis and the Role of Magnetization
Schumacher Ch, Herrmann IK, Bubenhofer SB, Gschwind S, Hirt AM, Beck-Schimmer B, Günther D, Stark W (2013), Quantitative Recovery of Magnetic Nanoparticles from Flowing Blood: Trace Analysis and the Role of Magnetization, in Advanced Functional Materials, 23, 4888.
Endotoxin removal by magnetic separation-based blood purification
Herrmann Inge K, Urner Martin, Graf Samuel, Schumacher Christoph M, Roth Z'graggen Birgit, Hasler Melanie, Stark Wendelin J, Beck-Schimmer Beatrice (2012), Endotoxin removal by magnetic separation-based blood purification, in Adv Health Mater, 2(6), 829-835.
Device for continuous extracorporeal blood purification using target-specific metal nanomagnets
Herrmann Inge K, Bernabei Riccardo E, Urner Martin, Grass Robert N, Beck-Schimmer Beatrice, Stark Wendelin J (2011), Device for continuous extracorporeal blood purification using target-specific metal nanomagnets, in Nephrol Dial Transplant., 26(9), 2948-2954.
Iron core/shell nanoparticles as magnetic drug carriers: possible interactions with the vascular compartment.
Herrmann Inge K, Urner Martin, Hasler Melanie, Roth-Z'Graggen Birgit, Aemisegger Caroline, Baulig Werner, Athanassiou Evagelos K, Regenass Stephan, Stark Wendelin J, Beck-Schimmer Beatrice (2011), Iron core/shell nanoparticles as magnetic drug carriers: possible interactions with the vascular compartment., in Nanomedicine (London, England), 6(7), 1199-213.
Therapeutic Blood Purification using Functionalized Core/Shell Nanomagnets
Herrmann IK, Urner Martin, Koehler FM, Hasler M, Roth-Z'graggen B, Grass R, Ziegler U, Beck-Schimmer B, Stark W (2011), Therapeutic Blood Purification using Functionalized Core/Shell Nanomagnets, in Small, 6(6), 1388.

Collaboration

Group / person Country
Types of collaboration
Klinik für Hämatologie, UniversitätsSpital Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Department of Anesthesiology University of Illinois Chicago United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
CLINAM Talk given at a conference Megaopportunities with a nano risk? Intravascular application of magnetic metal nano particles 23.06.2014 Basel, Switzerland Herrmann Inge; Stark Wendelin Jan; Beck Schimmer Beatrice;
Nanoconvention Talk given at a conference Magnetic nanoparticles: one step closer to the bedside? 21.05.2014 Brugg, Switzerland Beck Schimmer Beatrice; Stark Wendelin Jan;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Scientifica UZH/ETH Performances, exhibitions (e.g. for education institutions) 31.08.2013 ETH Zurich, Switzerland Schläpfer Martin; Beck Schimmer Beatrice; Herrmann Inge; Urner Martin Andreas; Schumacher Christoph;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Gesund sterben. Was uns die Medizin von morgen bringt German-speaking Switzerland 2013
Media relations: print media, online media Polyvalente Zwerge UZH News German-speaking Switzerland 2013
Media relations: print media, online media Magnetische Nanopartikel für die Blutreinigung UZH News German-speaking Switzerland 2012

Awards

Title Year
Master thesis award for Silvan Locher 'Carbon-coated magnetic nanoparticles: Interaction with the human blood coagulation system' (exceptional master thesis to the semester at the Faculty of Medicine, University of Zurich) 2014

Associated projects

Number Title Start Funding scheme
160283 Does anesthetic management have an impact on circulating tumor cells? 01.04.2015 Project funding

Abstract

This grant proposal aims at the elucidation of therapeutic applications and potential health risks of carbon protected magnetic metal nanoparticles (NPs). Carbon/metal nanomagnets benefit from their uniquely high mobility, the exceptionally specific surface area and the corresponding high capacity for reliable linking of functional molecules (high surface concentration of active substance), making them extremely effective drug carriers. The magneto-responsive properties allow control and targeting through non-destructive magnetic gradient fields. Current problems associated with the use of magnetic (micro)-particles are either their low binding capacity, or a bad response to magnetic fields, particularly for oxide-based materials. Carbon coated metal NPs contribute to overcoming these drawbacks as their high strength metal core allows rapid movement, yet their high specific surface area (10 - 10’000 times larger then microparticles) allows sufficient capacity to ligand binding. High saturation magnetization and low coercivity enable rapid distribution of nano-sized ferromagnetic metal particles in a liquid sample. They efficiently scan the whole liquid by Brownian diffusion and capture the targeted substance with their surface functionalities. Potentials and possible harms within the life cycle of carbon coated magnetic NPs will be assessed in this grant application. Regarding chances of this type of NPs, magnetic NPs will be evaluated focusing on the possibility of magnetically guiding drugs to a desired region in the human body (bringing chemotherapeutics to a tumor). In a second scenario, using magnetic metal NPs, target molecule isolation in a detoxification procedure in situations such as drug overdose or misbalance in inflammatory mediators will be evaluated. As the knowledge on human exposure of engineered metal NPs is still very limited - in contrast, oxide NP are under extended investigation - a detailed risk assessment is a prerequisite for a future therapeutic application. Therefore, key points of the life cycle of magnetic metal NPs will be evaluated (exposure of vascular compartment) and the liver (possible accumulation). The character of the interaction of magnetic metal NPs with endothelial, blood and hepatic cells will be assessed and possible inflammation reactions and/or toxicity will be determined. Additionally, bio-interaction during therapeutic application in the blood stream will be investigated regarding hemocompatibility, influence on blood coagulation, interaction with vascular endothelium and liver metabolism. This project thereby lays the groundwork to bringing this promising new technology from bench to bedside.
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