Remote magnetic targeting of iron oxide nanoparticles for cardiovascular diagnosis and therapeutic drug delivery: where are we now?

Magnetic resonance imaging (MRI) allows for an accurate assessment of both functional and structural cardiac parameters, and thereby appropriate diagnosis and validation of cardiovascular diseases. The diagnostic yield of cardiovascular MRI examinations is often increased by the use of contrast agents that are almost exclusively based on gadolinium compounds. Another clinically approved contrast medium is composed of superparamagnetic iron oxide nanoparticles (IONs). These particles may expand the field of contrast-enhanced cardiovascular MRI as recently shown in clinical studies focusing on acute myocardial infarction (AMI) and atherosclerosis. Furthermore, IONs open up new research opportunities such as remote magnetic drug targeting (MDT). The approach of MDT relies on the coupling of bioactive molecules and magnetic nanoparticles to form an injectable complex. This complex, in turn, can be attracted to and retained at a desired target inside the body with the help of applied magnetic fields. In comparison to common systemic drug applications, MDT techniques promise both higher concentrations at the target site and lower concentrations elsewhere in the body. Moreover, concurrent or subsequent MRI can be used for noninvasive monitoring of drug distribution and successful delivery to the desired organ in vivo. This review does not only illustrate the basic conceptual and biophysical principles of IONs, but also focuses on new research activities and achievements in the cardiovascular field, mainly in the management of AMI. Based on the presentation of successful MDT applications in preclinical models of AMI, novel approaches and the translational potential of MDT are discussed.

[1]  Andreas Radbruch,et al.  High gradient magnetic cell separation with MACS. , 1990, Cytometry.

[2]  P Reichardt,et al.  Clinical experiences with magnetic drug targeting: a phase I study with 4'-epidoxorubicin in 14 patients with advanced solid tumors. , 1996, Cancer research.

[3]  P A Voltairas,et al.  Hydrodynamics of magnetic drug targeting. , 2002, Journal of biomechanics.

[4]  R. Judd,et al.  Assessment of Myocardial Viability by Cardiovascular Magnetic Resonance Imaging , 2022 .

[5]  P. Reimer,et al.  Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications , 2003, European Radiology.

[6]  Alan P Koretsky,et al.  Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells. , 2003, Blood.

[7]  Q. Pankhurst,et al.  Applications of magnetic nanoparticles in biomedicine , 2003 .

[8]  Ajay Kumar Gupta,et al.  Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. , 2005, Biomaterials.

[9]  C. Alexiou,et al.  A High Field Gradient Magnet for Magnetic Drug Targeting , 2006, IEEE Transactions on Applied Superconductivity.

[10]  Samir Mitragotri,et al.  Role of target geometry in phagocytosis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Frank J Rybicki,et al.  Biochemical safety profiles of gadolinium‐based extracellular contrast agents and nephrogenic systemic fibrosis , 2007, Journal of magnetic resonance imaging : JMRI.

[12]  Leelee Ong,et al.  Gene delivery to the heart by magnetic nanobeads , 2007 .

[13]  A. Lu,et al.  Magnetic nanoparticles: synthesis, protection, functionalization, and application. , 2007, Angewandte Chemie.

[14]  Gary Friedman,et al.  High field gradient targeting of magnetic nanoparticle-loaded endothelial cells to the surfaces of steel stents , 2008, Proceedings of the National Academy of Sciences.

[15]  R. Kim,et al.  Performance of Delayed-Enhancement Magnetic Resonance Imaging With Gadoversetamide Contrast for the Detection and Assessment of Myocardial Infarction: An International, Multicenter, Double-Blinded, Randomized Trial , 2008, Circulation.

[16]  A. Tsourkas,et al.  Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells. , 2008, Biomaterials.

[17]  C. Murry,et al.  Systems approaches to preventing transplanted cell death in cardiac repair. , 2008, Journal of molecular and cellular cardiology.

[18]  B. Pützer,et al.  Enhanced thoracic gene delivery by magnetic nanobead‐mediated vector , 2008, The journal of gene medicine.

[19]  Q. Pankhurst,et al.  Progress in applications of magnetic nanoparticles in biomedicine , 2009 .

[20]  J. W. Haverkort,et al.  Computational Simulations of Magnetic Particle Capture in Arterial Flows , 2009, Annals of Biomedical Engineering.

[21]  P. Libby,et al.  Molecular Imaging of Innate Immune Cell Function in Transplant Rejection , 2009, Circulation.

[22]  Samir Mitragotri,et al.  Designer Biomaterials for Nanomedicine , 2009 .

[23]  Martin J Graves,et al.  The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. , 2009, Journal of the American College of Cardiology.

[24]  Samir Mitragotri,et al.  Physical approaches to biomaterial design. , 2009, Nature materials.

[25]  P. Couvreur,et al.  Nanocarriers’ entry into the cell: relevance to drug delivery , 2009, Cellular and Molecular Life Sciences.

[26]  Thomas J. Webster,et al.  Safety of nanoparticles : from manufacturing to medical applications , 2009 .

[27]  T. Pellegrino,et al.  From iron oxide nanoparticles towards advanced iron-based inorganic materials designed for biomedical applications. , 2010, Pharmacological research.

[28]  R. Pazdur,et al.  FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease , 2010, American journal of hematology.

[29]  K. Krishnan Biomedical Nanomagnetics: A Spin Through Possibilities in Imaging, Diagnostics, and Therapy , 2010, IEEE Transactions on Magnetics.

[30]  Yong Eun Koo Lee,et al.  Nanoparticles for cancer diagnosis and therapy , 2010 .

[31]  Richard D. White,et al.  ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. , 2010, Circulation.

[32]  V. Bulmus,et al.  The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications , 2010 .

[33]  E. Marbán,et al.  Magnetic Targeting Enhances Engraftment and Functional Benefit of Iron-Labeled Cardiosphere-Derived Cells in Myocardial Infarction , 2010, Circulation research.

[34]  Miqin Zhang,et al.  Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. , 2010, Advanced drug delivery reviews.

[35]  R. Morin,et al.  ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT 2010 expert consensus document on coronary computed tomographic angiography: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. , 2010, Journal of the American College of Cardiology.

[36]  Anthony N Price,et al.  Targeted magnetic delivery and tracking of cells using a magnetic resonance imaging system. , 2010, Biomaterials.

[37]  K. Nicolay,et al.  Relaxivity of Nanoparticles for Magnetic Resonance Imaging , 2010 .

[38]  Manesh R. Patel,et al.  ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. , 2010, Circulation.

[39]  Morteza Mahmoudi,et al.  Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles. , 2011, Advances in colloid and interface science.

[40]  W. Wilson,et al.  Targeting hypoxia in cancer therapy , 2011, Nature Reviews Cancer.

[41]  Calum Gray,et al.  Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide: A Pilot Study , 2011, Circulation. Cardiovascular imaging.

[42]  B. Shapiro,et al.  The Behaviors of Ferro-Magnetic Nano-Particles In and Around Blood Vessels under Applied Magnetic Fields. , 2011, Journal of magnetism and magnetic materials.

[43]  D. Nishimura,et al.  A molecular MRI probe to detect treatment of cardiac apoptosis in vivo , 2011, Magnetic resonance in medicine.

[44]  Tom MacGillivray,et al.  Ultrasmall Superparamagnetic Particles of Iron Oxide in Patients With Acute Myocardial Infarction: Early Clinical Experience , 2012, Circulation. Cardiovascular imaging.

[45]  A. Nemirovski,et al.  Optimal Halbach Permanent Magnet Designs for Maximally Pulling and Pushing Nanoparticles. , 2012, Journal of magnetism and magnetic materials.

[46]  C. A. Shaw,et al.  In Vivo Mononuclear Cell Tracking Using Superparamagnetic Particles of Iron Oxide: Feasibility and Safety in Humans , 2012, Circulation Cardiovascular Imaging.

[47]  Arash Komaee,et al.  Towards Control of Magnetic Fluids in Patients: Directing Therapeutic Nanoparticles to Disease Locations , 2012, IEEE Control Systems.

[48]  Eduardo Marbán,et al.  Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit after Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/Reperfusion , 2012, Cell transplantation.

[49]  K. Dassler,et al.  Studying the effect of particle size and coating type on the blood kinetics of superparamagnetic iron oxide nanoparticles , 2012, International journal of nanomedicine.

[50]  H. Sorg,et al.  Targeted Delivery of Human VEGF Gene via Complexes of Magnetic Nanoparticle-Adenoviral Vectors Enhanced Cardiac Regeneration , 2012, PloS one.

[51]  Shan X. Wang,et al.  Fluorescent magnetic nanoparticles for magnetically enhanced cancer imaging and targeting in living subjects. , 2012, ACS nano.

[52]  K. Seung,et al.  Noninvasive Assessment of Myocardial Inflammation by Cardiovascular Magnetic Resonance in a Rat Model of Experimental Autoimmune Myocarditis , 2012, Circulation.

[53]  C. Faber,et al.  Early detection of lung inflammation: Exploiting T1‐effects of iron oxide particles using UTE MRI , 2012, Magnetic resonance in medicine.

[54]  J. Gillard,et al.  Sequential imaging of asymptomatic carotid atheroma using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging: a feasibility study. , 2013, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[55]  J. Ge,et al.  The effect of nonuniform magnetic targeting of intracoronary-delivering mesenchymal stem cells on coronary embolisation. , 2013, Biomaterials.

[56]  Patrick Couvreur,et al.  Stimuli-responsive nanocarriers for drug delivery. , 2013, Nature materials.

[57]  S. Majetich,et al.  Magnetic nanoparticles , 2013, Handbook of Magnetism and Magnetic Materials.

[58]  J. Ge,et al.  Magnetic targeting enhances retrograde cell retention in a rat model of myocardial infarction , 2013, Stem Cell Research & Therapy.

[59]  Julien Cohen-Adad,et al.  Pushing the limits of in vivo diffusion MRI for the Human Connectome Project , 2013, NeuroImage.

[60]  Ali Yilmaz,et al.  Imaging of myocardial infarction using ultrasmall superparamagnetic iron oxide nanoparticles: a human study using a multi-parametric cardiovascular magnetic resonance imaging approach. , 2013, European heart journal.

[61]  R. Jain,et al.  Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. , 2013, Cancer research.

[62]  Richard C. Willson,et al.  Tuning the Magnetic Properties of Nanoparticles , 2013, International journal of molecular sciences.

[63]  U. Karst,et al.  Bacteria tracking by in vivo magnetic resonance imaging , 2013, BMC Biology.

[64]  M. Mahmoudi,et al.  Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges , 2014, Expert opinion on drug delivery.

[65]  Erica M. Cherry,et al.  A comprehensive model of magnetic particle motion during magnetic drug targeting , 2014 .

[66]  K. Cheng,et al.  Magnetic targeting of cardiosphere-derived stem cells with ferumoxytol nanoparticles for treating rats with myocardial infarction. , 2014, Biomaterials.

[67]  E. Marbán,et al.  Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting , 2014, Nature Communications.

[68]  R. Weissleder,et al.  Imaging macrophages with nanoparticles. , 2014, Nature materials.

[69]  J. Ge,et al.  Comparison of Magnetic Intensities for Mesenchymal Stem Cell Targeting Therapy on Ischemic Myocardial Repair: High Magnetic Intensity Improves Cell Retention but Has no Additional Functional Benefit , 2015, Cell transplantation.

[70]  A. Bianco,et al.  Multifunctional carbon nanomaterial hybrids for magnetic manipulation and targeting. , 2015, Biochemical and biophysical research communications.

[71]  Zhaohui Wu,et al.  Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications , 2015, Science and technology of advanced materials.

[72]  Benjamin Shapiro,et al.  Open challenges in magnetic drug targeting. , 2015, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[73]  Mark F. Lythgoe,et al.  Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting , 2015, Nature Communications.

[74]  S. Eberhardt,et al.  Iron-based superparamagnetic nanoparticle contrast agents for MRI of infection and inflammation. , 2015, AJR. American journal of roentgenology.

[75]  Radek Zboril,et al.  Tailored functionalization of iron oxide nanoparticles for MRI, drug delivery, magnetic separation and immobilization of biosubstances. , 2015, Biotechnology advances.

[76]  M. Lythgoe,et al.  Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles. , 2015, Regenerative medicine.

[77]  V. Préat,et al.  Iron oxide-loaded nanotheranostics: major obstacles to in vivo studies and clinical translation. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[78]  S. Mitragotri,et al.  Elasticity of nanoparticles influences their blood circulation, phagocytosis, endocytosis, and targeting. , 2015, ACS nano.