We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Magnetic nanoparticles and their applications in medicine

    Etienne Duguet

    † Author for correspondence

    Institut de Chimie de la Matière Condensée de Bordeaux, CNRS/University Bordeaux-1, 87 avenue du Dr Albert Schweitzer, F-33608 Pessac Cedex, France.

    ,
    Sébastien Vasseur

    Institut de Chimie de la Matière Condensée de Bordeaux, CNRS/University Bordeaux-1, 87 avenue du Dr Albert Schweitzer, F-33608 Pessac Cedex, France.

    ,
    Stéphane Mornet

    Institut de Chimie de la Matière Condensée de Bordeaux, CNRS/University Bordeaux-1, 87 avenue du Dr Albert Schweitzer, F-33608 Pessac Cedex, France.

    &
    Jean-Marie Devoisselle

    UMR CNRS/ENSCM/UM1 5618, Institut Charles Gerhardt, 8, rue de l'Ecole Normale, F-34296 Montpellier Cedex 5, France

    ,
    Published Online:https://doi.org/10.2217/17435889.1.2.157

    Magnetic nanoparticles have attracted attention in modern medicine and pharmacology owing to their potential usefulness as contrast agents for MRI, as colloidal mediators for cancer magnetic hyperthermia or as active constituents of drug-delivery platforms. This review examines these in vivo applications through an understanding of the involved problems and the current and future possibilities for resolving them. A special emphasis is placed upon magnetic nanoparticle requirements from a physical viewpoint (e.g., relaxivity for MRI, specific absorption rate for hyperthermia and magnetic guidance), the factors affecting their biodistribution after intravenous injection (e.g., size and surface hydrophobic/hydrophilic balance) and the solutions envisaged for enhancing their half-life in the blood compartment and in targeting tumor cells.

    Bibliography

    • Häfeli U: The history of magnetism in medicine. In: Magnetism in Medicine. Andrä W, Nowak H (Eds). Wiley-VCH, Berlin, Germany, 15–34 (1998).
    • Bailey RE, Smith AM, Nie S: Quantum dots in biology and medicine. Physica E25,1–12 (2004).
    • West JL, Halas NJ: Engineered nanomaterials for biophotonics applications: improving sensing, imaging, and therapeutics. Annu. Rev. Biomed. Eng.5,285–292 (2003).
    • Moghimi SM, Szebeni J: Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog. Lipid Res.42(6),463–478 (2003).
    • Monfardini C, Veroneses FM: Stabilization of substances in circulation. Bioconjug. Chem.9(4),418–450 (1998).
    • Mornet S, Vasseur S, Grasset F et al.: Magnetic nanoparticle design for medical diagnosis and therapy. J. Mater. Chem.14,2161–2175 (2004).
    • Sonvico F, Dubernet C, Colombo P et al.: Metallic colloid nanotechnology, applications in diagnosis and therapeutics. Curr. Pharm. Des.11,2091–2105 (2005).
    • Berry CC, Curtis ASG: Functionalisation of magnetic nanoparticles for applications in biomedicine. J. Phys. D Appl. Phys.36,R198–R206 (2003).
    • Bahadur D, Giri J: Biomaterials and magnetism. Sadhana28(3–4),639–656 (2003).
    • 10  Ito A, Shinkai M, Honda H et al.: Medical application of functionalized magnetic nanoparticles. J. Biosci. Bioeng.100(1),1–11 (2005).
    • 11  Tartaj P, del Puerto Morales M, Veintemillas-Verdaguer S et al.: The preparation of magnetic nanoparticles for applications in biomedicine. J. Phys. D Appl. Phys.36(13),R182–R197 (2003).
    • 12  Gupta AK, Gupta MP: Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials26,3995–4021 (2005).
    • 13  Pankhurst QA, Connolly J, Jones SK et al.: Applications of magnetic nanoparticles in biomedicine. J. Phys. D Appl. Phys.36,R167–R181 (2003).
    • 14  Berkov D: Basic physical principles. In: Magnetism in Medicine. Andrä W, Nowak H (Eds). Wiley-VCH, Berlin, Germany, 35–73 (1998).
    • 15  Moghimi SM, Hunter AC, Murray JC: Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol. Rev.53(2),283–318 (2001).
    • 16  Hume DA, Ross IL, Himes SR et al.: The mononuclear phagocyte system revisited. J. Leukoc. Biol.72,621–627 (2002).
    • 17  Chiannilkulchai N, Driouich Z, Benoit JP et al.: Doxorubucin loaded nanoparticles: increased efficiency in murine hepatic metastases. Sel. Cancer Ther.5,1–11 (1990).
    • 18  Pinto-Alphandary H, Andremont A, Couvreur P: Targeted delivery of antibiotics using liposomes and nanoparticles: research and applications. Int. J. Anitmicrob. Agents13,155–168 (2000).
    • 19  Choi SW, Kim WS, Kim JH: Surface modification of functional nanoparticles for controlled drug delivery. J. Dispersion Sci. Technol.24(3–4),475–487 (2003).
    • 20  Zalipsky S: Functionalized poly(ethylene glycol) for preparation of biologically relevant conjugates. Bioconjug. Chem.6(2),150–165 (1995).
    • 21  Peracchia MT: Stealth nanoparticles for intravenous administration. STP Pharma. Sci.13(3),155–161 (2003).
    • 22  Weissleder R, Bogdanov A, Neuwelt EA et al.: Long-circulating iron oxides for MR imaging. Adv. Drug Deliv. Rev.16(2–3),321–334 (1995).
    • 23  Sudimack J, Lee RJ: Targeted drug delivery via the folate receptor. Adv. Drug Deliv. Rev.41,147–162 (2000).
    • 24  Bonnemain B: Superparamagnetic agents in magnetic resonance imaging: physicochemical characteristics and clinical applications a review. J. Drug Target.6(3),167–174 (1998).
    • 25  Bjornerud A, Johansson L: The utility of superparamagnetic contrast agents in MRI: theoretical consideration and applications in the cardiovascular system. NMR Biomed.17,465–477 (2004).
    • 26  Okuhata Y: Delivery of diagnostic agents for magnetic resonance imaging. Adv. Drug Deliv. Rev.37,121–137 (1999).
    • 27  Jung CW: Surface properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn. Reson. Imaging13(5),675–691 (1995).
    • 28  Högemann D, Josephson L, Weissleder R et al.: Improvement of MRI probes to allow efficient detection of gene expression. Bioconjug. Chem.11(6),941–946 (2000).
    • 29  Lesniak C, Schiestel T, Nass R et al.: Synthesis and surface modification of deagglomerated superparamagnetic nanoparticles. Mater. Res. Soc. Symp. Proc.432,169–174 (1997).
    • 30  Mornet S, Portier J, Duguet E: A method for synthesis and functionalization of ultrasmall superparamagnetic covalent carriers based on maghemite and dextran. J. Magn. Magn. Mater.293,127–134 (2005).
    • 31  Weissleder R, Stark DD, Engelstad BL et al.: Superparamagnetic iron oxide: pharmacokinetics and toxicity. AJR Am. J. Roentgenol.152,167–173 (1989).
    • 32  Papisov MI, Bogdanov A, Schaffer B et al.: Colloidal magnetic resonance contrast agents: effect of particule surface on biodistribution. J. Magn. Magn. Mater.122,383–386 (1993).
    • 33  Weissleder R, Elizondo G, Wittenberg J et al.: Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology175,489–493 (1990).
    • 34  Brusentsov NA, Gogosov VV, Brusentsova TN et al.: Evaluation of ferromagnetic fluids and suspensions for the site-specific radiofrequency-induced hyperthermia of MX11 sarcoma cells in vitro. J. Magn. Magn. Mater.225,113–117 (2001).
    • 35  Wada S, Yue L, Tazawa K et al.: New local hyperthermia using dextran magnetite complex (DM) for oral cavity: experimental study in normal hamster tongue. Oral Dis.7,192–195 (2001).
    • 36  Weinmann HJ, Ebert W, Misselwitz B et al.: Tissue-specific MR contrast agents. Eur. J. Radiol.46,33–44 (2003).
    • 37  Reimer P, Balzer T: Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development and applications. Eur. Radiol.13,1266–1276 (2003).
    • 38  Jung CW, Jacobs P: Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn. Reson. Imaging13(5),661–674 (1995).
    • 39  Weissleder R, Heautot JF, Schaffer BK et al.: MR lymphography: study of high-efficiency lymphotropic agent. Radiology191,225–230 (1994).
    • 40  Guimaraes R, Clement O, Bittoun J et al.: MR lymphography with superparamagnetic iron nanoparticles in rats: pathologic basis for contrast enhancement. AJR Am. J. Roentgenol.162,201–207 (1994).
    • 41  Bellin MF, Lebleu L, Meric JB: Evaluation of retroperitoneal and pelvic lymph node metastases with MRI and MR lymphangiography. Abdom. Imaging28(2),155–163 (2003).
    • 42  Kellar KE, Fujii DK, Gunther WHH et al.: “NC 100150”, a preparation of iron oxide nanoparticles ideal for positive-contrast MR angiography. Magn. Reson. Mater. Phys. Biol. Med.8(3),207–213 (1999).
    • 43  Bulte JWM, Kraitchman DL: Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed.17,484–499 (2004).
    • 44  Weissleder R, Lee AS, Fischman AJ et al.: Polyclonal human immunoglobin G labeled with polymeric iron oxide: antibody MR imaging. Radiology181(1),245–249 (1991).
    • 45  Tiefenauer LX, Kühne G, Andres RY: Antibody-magnetite nanoparticles: in vitro characterization of a potential tumor-specific contrast agent for magnetic resonance imaging. Bioconjug. Chem.4,347–352 (1993).
    • 46  Suzuki M, Honda H, Kobayashi T et al.: Development of a target-directed magnetic resonance contrast agent using monoclonal antibody-conjugated magnetic particles. Brain Tumor Pathol.13,127–132 (1996).
    • 47  Remsen LG, McCormick CI, Roman-Goldstein S et al.: MR of carcinoma-spectific monoclonal antibody conjugated to monocrystalline iron oxide nanoparticles : the potential for non invasive diagnostic. Am. J. Neuroradiol.17(3),411–418 (1996).
    • 48  Suwa T, Ozawa S, Ueda M et al.: Magnetic resonance imaging of oesophageal squamous cell carcinoma using magnetite particles coated with anti-epidermal growth factor receptor antibody. Int. J. Cancer75,626–634 (1998).
    • 49  Zhang Y, Kohler N, Zhang M: Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials23,1553–1561 (2002).
    • 50  Kohler N, Fryxell GE, Zhang M: A bifunctional poly(ethylene glycol) silane immobilized on metallic oxide-based nanoparticles for conjugation with cell targeting agents. J. Am. Chem. Soc.126(23),7206–7211 (2004).
    • 51  Choi HC, Choi SR, Zhou R et al.: Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-target delivery. Acad. Radiol.11,996–1004 (2004).
    • 52  Sonvico F, Mornet S, Vasseur S et al.: Folate-conjugated iron oxide nanoparticles for solid tumor targeting as potential specific magnetic hyperthermia mediators: synthesis, physico-chemical characterisation and in vitro experiments. Bioconjug. Chem.16,1181–1188 (2005).
    • 53  Högemann-Savellano D, Bos E, Blondet C et al.: The transferrin receptor: a potential molecular imaging marker for human cancer. Neoplasia5(6),495–506 (2003).
    • 54  Högemann D, Ntziachristos V, Josephson L et al.: High throughput magnetic resonance imaging for evaluating targeted nanoparticle probes. Bioconjug. Chem.13,116–121 (2002).
    • 55  Nielsen OS, Horsman M, Overgaard J: A future for hyperthermia in cancer treatment? Eur. J. Cancer37,1587–1589 (2001).
    • 56  Overgaard K, Overgaard J: Investigations on the possibility of a thermic tumour therapy – I. Eur. J. Cancer8,65–78 (1972).
    • 57  Moroz P, Jones SK, Gray BN: Status of hyperthermia in the treatment of advanced liver cancer. J. Surg. Oncol.77,259–269 (2001).
    • 58  Jordan A, Scholz R, Wust P et al.: Magnetic fluid hyperthermia (MFH): cancer treatment with AC magnetic induced excitation of biocompatible superparamagnetic nanoparticles. J. Magn. Magn. Mater.201,413–419 (1999).
    • 59  Overgaard J: The current and potential role of hyperthermia in radiotherapy. Int. J. Radiat. Oncol. Biol. Phys.16(3),535–549 (1989).
    • 60  Dubois JB: Hyperthermie: principes, techniques. Place actuelle dans le traitement des cancers. Bull. Cancer Radiother.82,207–224 (1995).
    • 61  Owens SD, Gasper PW: Hyperthermic therapy for HIV infection. Med. Hypotheses44,235–242 (1995).
    • 62  Gel'vich EA, Mazokhin VN: Technical aspects of electromagnetic hyperthermia in medicine. Crit. Rev. Biomed. Eng.29(1),77–97 (2001).
    • 63  Moroz P, Jones SK, Gray BN: Magnetically mediated hyperthermia: current status and future directions. Int. J. Hyperthermia18(4),267–284 (2002).
    • 64  Andrä W: Magnetic hyperthermia. In: Magnetism in Medicine. Andrä W, Nowak H (Eds). Wiley-VCH, Berlin, Germany, 455–470 (1998).
    • 65  Hill DA: Further studies of human whole-body radiofrequency absorption rates. Bioelectromagnetics6(1),33–40 (1985).
    • 66  Le B, Shinkai M, Kitade T et al.: Preparation of tumor-specific magnetoliposomes and their application for hyperthermia. J. Chem. Eng. Jpn34(1),66–72 (2001).
    • 67  Gneveckow U, Jordan A, Scholz R et al.: Description and characterization of the novel hyperthermia- and thermoablation-system MFH (R) 300F for clinical magnetic fluid hyperthermia. Med. Phys.31(6),1444–1451 (2004).
    • 68  Jordan A, Wust P, Scholz R et al.: Cellular uptake of magnetic fluid particles and their effects on human adenocarcinoma cells exposed to AC magnetic fields in vitro. Int. J. Hyperthermia12(6),705–722 (1996).
    • 69  Jordan A, Scholz R, Wust P et al.: Endocytosis of dextran and silan-coated magnetite nanoparticles and the effect of intracellular hyperthermia on human mammary carcinoma cells in vitro. J. Magn. Magn. Mater.194,185–196 (1999).
    • 70  Jordan A, Scholz R, Wust P et al.: Effects of magnetic fluid hyperthermia (MFH) on C3H mammary carcinoma in vivo. Int. J. Hyperthermia13(6),587–605 (1997).
    • 71  Johannsen M, Jordan A, Scholz R et al.: Evaluation of magnetic fluid hyperthermia in a standard rat model of prostate cancer. J. Endurolog.18(5),495–500 (2004).
    • 72  Johannsen M, Gneveckow U, Eckelt L et al.: Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique. Int. J. Hyperthermia21(7),637–647 (2005).
    • 73  Kawai N, Ito A, Nakahara Y et al.: Anticancer effect of hyperthermia on prostate cancer mediated by magnetite cationic liposomes and immune-response induction in transplanted syngeneic rats. Prostate64,373–381 (2005)
    • 74  Tanaka K, Ito A, Kobayashi T et al.: Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles. Int. J. Cancer116,624–633 (2005).
    • 75  Kawai N, Ito A, Nakahara Y et al.: Complete regression of esperimental prostate cancer in nude mice by repeated hyperthermia using magnetite cationic liposomes and a newly developed solenoid containing a ferrite core. Prostate66,718–727 (2006).
    • 76  Suzuki M, Shinkai M, Kamihira M et al.: Preparation and characteristics of magnetite-labelled antibody with the use of poly(ethylene glycol) derivatives. Biotechnol. Appl. Biochem.21,335–345 (1995).
    • 77  DeNardo SJ, DeNardo GL, Miers LA et al.: Development of tumor targeting bioprobes (111In-chimeric L6 monoclonal antibody nanoparticles) for alternating magnetic field cancer therapy. Clin. Cancer Res.11,7087s–7092s (2005).
    • 78  Quesson B, Vimeux F, Salomir R et al.: Automatic control of hyperthermic therapy based on real-time fourier analysis of MR temperature maps. Magn. Reson. Med.47(6),1065–1072 (2002).
    • 79  Deger S, Taymoorian K, Boehmer D et al.: Thermoradiotherapy using interstitial self-regulating thermoseeds: an intermediate analysis of a phase II trial. Eur. Urol.45(5),574–579 (2004).
    • 80  Kuznetsov AA, Shlyakhtin OA, Brusentsov NA et al.: “Smart” mediators for self-controlled inductive heating. Eur. Cell. Mater.3(Suppl. 2),75–77 (2002).
    • 81  Vasseur S, Duguet E, Portier J et al.: Lanthanum manganese perovskite nanoparticles as possible in vivo mediators for magnetic hyperthermia. J. Magn. Magn. Mater.302,315–320 (2006).
    • 82  Rabin Y: Is intracellular hyperthermia superior to extracellular hyperthermia in the thermal sense? Int. J. Hyperthermia18(3),194–202 (2002).
    • 83  Lübbe AS, Alexiou C, Bergemann C: Clinical applications of magnetic drug targeting. J. Surg. Res.95,200–206 (2001).
    • 84  Edelman ER, Kost J, Bobeck T et al.: Regulation of drug release from polymer matrices by oscillating magnetic fields. J. Biomed. Mater. Res.19,67–83 (1985).
    • 85  Sershen SR, Westcott SL, Halas NJ et al.: Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery. J. Biomed. Mater. Res.51,293–298 (2000).
    • 86  Kreuter J: Nanoparticutate systems for brain delivery drugs. Adv. Drug Deliv. Rev.47,65–81 (2001).
    • 87  Lockman PR, Mumper RJ, Khan MA et al.: Nanoparticle technology for drug delivery across the blood–brain barrier. Drug Dev. Ind. Pharm.28(1),1–12 (2002).
    • 88  Couvreur P, Brigger I, Dubernet C: Nanoparticles in cancer therapy and diagnosis. Adv. Drug Deliv. Rev.54(5),631–651 (2002).
    • 89  Kumar MNV: Nano and microparticles as controlled drug delivery devices. J. Pharm. Pharm. Sci.3(2),234–258 (2000).
    • 90  Ghosh PK: Hydrophilic polymeric nanoparticles as drug carriers. Indian J. Biochem. Biophys.37,273–282 (2000).
    • 91  Mordon S, Desmettre T, Devoisselle JM et al.: Selective laser photocoagulation of blood vessels in a hamster skin flap model using a specific ICG formulation. Laser Surg. Med.21(4),365–373 (1997).
    • 92  Wallis F, Gilbert FJ: Magnetic resonance imaging in oncology: an overview. JR Coll. Surg. Edinb.44,117–125 (1999).
    • 93  Harisinghani MG, Barentsz J, Hahn PF et al.: Non invasive detection of clinically occult lymph-node metastases in prostate cancer. N. Engl. J. Med.348,2491–2499 (2003).
    • 101  MagForce Nanotechnologies AG www.magforce.de/en/
    • 201  CANADIAN PATENTS AND DEVELOPMENT LIMITED.: US4452773 (1984).
    • 202  ADVANCED MAGNETICS, INC.: US5248492 (1993).
    • 203  INSTITUT FUR NEUE MATERIALIEN GEM. GmbH: US6541039 (2003).