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Nucleic acid delivery using magnetic nanoparticles: the Magnetofection™ technology

    ,
    Cédric Sapet

    OZ Biosciences, Parc Scientifique de Luminy – Zone Entreprises, 163 Avenue de Luminy, Case 922, 13 288 Marseille cedex 9, France

    ,
    Loic Le Gourrierec

    OZ Biosciences, Parc Scientifique de Luminy – Zone Entreprises, 163 Avenue de Luminy, Case 922, 13 288 Marseille cedex 9, France

    ,
    Elodie Bertosio

    OZ Biosciences, Parc Scientifique de Luminy – Zone Entreprises, 163 Avenue de Luminy, Case 922, 13 288 Marseille cedex 9, France

    &
    Olivier Zelphati

    OZ Biosciences, Parc Scientifique de Luminy – Zone Entreprises, 163 Avenue de Luminy, Case 922, 13 288 Marseille cedex 9, France

    Published Online:https://doi.org/10.4155/tde.11.12

    In recent years, gene therapy has received considerable interest as a potential method for the treatment of numerous inherited and acquired diseases. However, successes have so far been hampered by several limitations, including safety issues of viral-based nucleic acid vectors and poor in vivo efficiency of nonviral vectors. Magnetofection™ has been introduced as a novel and powerful tool to deliver genetic material into cells. This technology is defined as the delivery of nucleic acids, either ‘naked’ or packaged (as complexes with lipids or polymers, and viruses) using magnetic nanoparticles under the guidance of an external magnetic field. This article first discusses the principles of the Magnetofection technology and its benefits as compared with standard transfection methods. A number of relevant examples of its use, both in vitro and in vivo, will then be highlighted. Future trends in the development of new magnetic nanoparticle formulations will also be outlined.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

    Bibliography

    • Kohn DB, Candotti F. Gene therapy fulfilling its promise. N. Engl. J. Med.360(5),518–521 (2009).Crossref, Medline, CASGoogle Scholar
    • Trollet C, Athanasopoulos T, Popplewell L, Malerba A, Dickson G. Gene therapy for muscular dystrophy: current progress and future prospects. Expert Opin. Biol. Therapeut.9(7),849–866 (2009).Crossref, Medline, CASGoogle Scholar
    • Williams DA. Gene therapy continues to mature and face challenges. Mol. Ther.17(8),1305–1306 (2009).Crossref, Medline, CASGoogle Scholar
    • Aiuti A, Roncarolo MG. Ten years of gene therapy for primary immune deficiencies. Hematology2009,682–689 (2009).CrossrefGoogle Scholar
    • Zallen DT. US gene therapy in crisis. Trends Genet.16,272–275 (2000).Crossref, MedlineGoogle Scholar
    • Pike-Overzet K, van der Burg M, Wagemaker G, van Dongen JJM, Staal FJT. New insights and unresolved issues regarding insertional mutagenesis in X-linked SCID gene therapy. Mol. Ther.15,1910–1916 (2007).Crossref, Medline, CASGoogle Scholar
    • Kostarelos K, Miller AD. What role can chemistry play in cationic liposome-based gene therapy research today? Adv. Genet.53,69–118 (2005).CrossrefGoogle Scholar
    • Li W, Szoka Jr FC. Lipid-based nanoparticles for nucleic acid delivery. Pharm. Res.24,438–449 (2007).Crossref, MedlineGoogle Scholar
    • Mintzer MA, Simanek EE. Nonviral vectors for gene delivery. Chem. Rev.109,259–302 (2009).▪ Comprehensive review on lipid-based gene delivery.Crossref, Medline, CASGoogle Scholar
    • 10  Tros de Ilarduya C, Sun Y, Duzgunes N. Gene delivery by lipoplexes and polyplexes. Eur. J. Pharm. Sci.40(3),159–170 (2010).Crossref, Medline, CASGoogle Scholar
    • 11  Bally MB, Harvie P, Wong FMP, Kong S, Wasan EK, Reimer DL. Biological barriers to cellular delivery of lipid-based DNA carriers. Adv. Drug. Deliv. Rev.38,291–315 (1999).Crossref, Medline, CASGoogle Scholar
    • 12  Mehier-Humbert S, Guy RH. Physical methods for gene transfer: improving the kinetics of gene delivery into cells. Adv. Drug. Deliv. Rev.57,733–753 (2005).Crossref, Medline, CASGoogle Scholar
    • 13  Woodle MC, Lasic DD. Sterically stabilized liposomes. Biochim. Biophys. Acta1113,171–199 (1992).Crossref, Medline, CASGoogle Scholar
    • 14  Deonarain MP. Ligand-targeted receptor-mediated vectors for gene delivery. Exp. Opin. Ther. Patents8(1),53–69 (1998).Crossref, CASGoogle Scholar
    • 15  Sapet C, Le Gourrierec L, Schillinger U et al. Magnetofection: magnetically assisted and targeted nucleic acids delivery. Drug Deliv. Technol.10(1),24–29 (2010).CASGoogle Scholar
    • 16  Sapet C, Laurent N, Le Gourrierec L, Augier S, Zelphati O. In vitro and in vivo Magnetofection: a move towards gene therapy. Ann. Biol. Clin.68(2),1–10 (2010).Google Scholar
    • 17  Corchero JL, Villaverde A. Biomedical applications of distally controlled magnetic nanoparticles. Trends Biotechnol.27,468–476 (2009).Crossref, Medline, CASGoogle Scholar
    • 18  Sun C, Lee JSH, Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Adv. Drug Deliv. Rev.60,1252–1265 (2008).Crossref, Medline, CASGoogle Scholar
    • 19  Arruebo M, Fernandez-Pacheco R, Ibarra MR, Santamaria J. Magnetic nanoparticles for drug delivery. Nano Today2,22–32 (2007).CrossrefGoogle Scholar
    • 20  Pankhust QA, Connolly J, Jones SK, Dobson J. Applications of magnetic nanoparticles in biomedicine. J. Phys. D. Appl. Phys.36,R167–R181 (2003).CrossrefGoogle Scholar
    • 21  Scherer F, Anton M, Schillinger U et al. Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Ther.9,102–109 (2002).Crossref, Medline, CASGoogle Scholar
    • 22  Schillinger U, Brill T, Rudolph C et al. Advances in Magnetofection – magnetically guided nucleic acid delivery. J. Magn. Magn. Mater.293,501–508 (2005).Crossref, CASGoogle Scholar
    • 23  Mykhalylyk O, Sanchez-Antequera Y, Vlaskou D, Plank C. Generation of nonviral gene transfer agents and Magnetofection in vitro. Nat. Protocols2,2391–2411 (2007).▪▪ Detailed protocol for the synthesis of magnetic nanoparticles (MNPs) suitable for nucleic acid delivery.Crossref, MedlineGoogle Scholar
    • 24  Mykhalylyk O, Sanchez-Antequera Y, Vlaskou D et al. Liposomal Magnetofection. Meth. Mol. Biol.605,487–525 (2010).▪▪ Step-by-step preparation of MNP-based gene-delivery vectors.Crossref, MedlineGoogle Scholar
    • 25  Massart R. Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Trans. Magn.17(2),1247–1248 (1981).CrossrefGoogle Scholar
    • 26  Chin AB, Yaacob II. Synthesis and characterization of magnetic iron oxide nanoparticles via w/o microemulsion and Massart’s procedure. J. Mater. Process Technol.191(1–3),235–237 (2007).Crossref, CASGoogle Scholar
    • 27  Albornoz C, Jacobo SE. Preparation of biocompatible magnetic film from aqueous ferrofluid. J. Magn. Magn. Mater.305(1),12–15 (2006).Crossref, CASGoogle Scholar
    • 28  Salazar-Alvarez G, Muhammed M, Zagorodni AA. Novel flow injection synthesis of iron oxide nanoparticles with narrow size distribution. Chem. Eng. Sci.61(14),4625–4633 (2006).Crossref, CASGoogle Scholar
    • 29  Dunin-Borkowski RE, McCartney MR, Frankel RB, Bazylinski DA, Posfai M, Buseck PR. Magnetic microstructure of magnetotactic bacteria by electron holography. Science282,1868–1870 (1998).Crossref, Medline, CASGoogle Scholar
    • 30  Plank C, Schillinger U, Scherer F et al. The Magnetofection method: using magnetic force to enhance gene delivery. Biol. Chem.384,737–747 (2003).Crossref, Medline, CASGoogle Scholar
    • 31  Khalil IA, Kogure K, Akita H, Harashima H. Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery. Pharmacol. Rev.58,32–45 (2006).Crossref, Medline, CASGoogle Scholar
    • 32  Pichon C, Billet L, Midoux P. Chemical vectors for gene delivery: uptake and intracellular trafficking. Curr. Opin. Chem. Biol.21,640–645 (2010).CASGoogle Scholar
    • 33  Sauer AM, de Bruin KG, Ruthardt N, Mykhaylyk O, Plank C, Brauchle C. Dynamics of magnetic lipoplexes studied by single particle tracking in living cells. J. Control. Release137,136–145 (2009).Crossref, Medline, CASGoogle Scholar
    • 34  Huth S, Lausier J, Gersting SW et al. Insights into the mechanism of Magnetofection using PEI-based magnetofectins for gene transfer. J. Gene Med.6(8),923–936 (2004).Crossref, Medline, CASGoogle Scholar
    • 35  Le Bihan O, Chèvre R, Mornet S, Garnier B, Pitard B, Lambert O. Probing the in vitro mechanism of action of cationic lipid/DNA lipoplexes at a nanometric scale. Nucl. Acids Res.39(4),1595–1609 (2011).Crossref, Medline, CASGoogle Scholar
    • 36  Boussif O, Lezoualch F, Zanta MA et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethyleneimine. Proc. Natl Acad. Sci. USA92,7297–7301 (1995).Crossref, Medline, CASGoogle Scholar
    • 37  Farhood H, Serbina N, Huang L. The role of dioleylphosphatidylethanolamine in cationic liposome mediated gene transfer. Biochim. Biophys. Acta1235,289–295 (1995).Crossref, MedlineGoogle Scholar
    • 38  Zelphati O, Szoka FC Jr. Mechanism of oligonucleotide release from cationic liposomes. Proc. Natl Acad. Sci. USA93,11493–11498 (1996).Crossref, Medline, CASGoogle Scholar
    • 39  Xu Y, Szoka JC Jr. Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry35,5616–5623 (1996).Crossref, Medline, CASGoogle Scholar
    • 40  Won YY, Sharma R, Konieczny SF. Missing pieces in understanding the intracellular trafficking of polycation/DNA complexes. J. Control. Release139,88–93 (2009).Crossref, Medline, CASGoogle Scholar
    • 41  Bulte JWM, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed.17,484–499 (2004).Crossref, Medline, CASGoogle Scholar
    • 42  Okon E, Pouliquen D, Okon D et al. Biodegradation of magnetite dextran nanoparticles in the rat. A histologic and biophysical study. Lab. Invest.71(6),895–903 (1994).Medline, CASGoogle Scholar
    • 43  Briley-Saebo K, Bjornerud A, Grant D, Ahlstrom H, Berg T, Kindberg GM. Hepatic cellular distribution and degradation of iron oxide nanoparticles following single intravenous injection in rats: implications for magnetic resonance imaging. Cell tissue Res.316(3),315–323 (2004).Crossref, Medline, CASGoogle Scholar
    • 44  Suh J, Wirtz D, Hanes J. Efficient active transport of gene nanocarriers to the cell nucleus. Proc. Natl Acad. Sci. USA100,3878–3882 (2003).Crossref, Medline, CASGoogle Scholar
    • 45  Dean DA, Strong DD, Zimmer WE. Nuclear entry of non viral vectors. Gene Ther.12,881–890 (2005).Crossref, Medline, CASGoogle Scholar
    • 46  Melchior F, Gerace L. Mechanisms of nuclear protein import. Curr. Opin. Cell. Biol.7,310–318 (1995).Crossref, Medline, CASGoogle Scholar
    • 47  Dworetzky SI, Lanford RE, Feldherr CM. The effects of variations in the number and sequence of targeting signals on nuclear uptake. J. Cell. Biol.107,1279–1287 (1988).Crossref, Medline, CASGoogle Scholar
    • 48  Steele IA, Dimaline R, Pritchard DM et al. Helicobacter and gastrin stimulate Reg1 expression in gastric epithelial cells through distinct promoter elements. Am. J. Physiol. Gastrointest. Liver Physiol.293,G347–G354 (2007).Crossref, Medline, CASGoogle Scholar
    • 49  Basile JR, Castilho RM, Williams VP, Gutkind JS. Semaphorin 4D provides a link between axon guidance processes and tumor-induced angiogenesis. Proc. Natl Acad. Sci. USA103,9017–9022 (2006).Crossref, Medline, CASGoogle Scholar
    • 50  Buerli T, Pellegrino C, Baer K et al. Efficient transfection of DNA or shRNA into neurons using Magnetofection. Nat. Protocols12(2),3090–3101 (2007).CrossrefGoogle Scholar
    • 51  Sbai O, Ferhat L, Bernard A et al. Vesicular trafficking and secretion of matrix metalloproteinases-2, -9 and tissue inhibitor of metalloproteinases-1 in neuronal cells. Mol. Cell. Neurosci.39,549–568 (2008).Crossref, Medline, CASGoogle Scholar
    • 52  Couchoux H, Allard B, Legrand C, Jacquemond V, Berthier C. Loss of caveolin-3 induced by the dystrophy-associated P104L mutation impairs L-type calcium channel function in mouse skeletal muscle cells. J. Physiol.580,745–754 (2007).Crossref, Medline, CASGoogle Scholar
    • 53  Megias J, Guillen MI, Clérigues V et al. Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E(2) production in osteoarthritic chondrocytes. Biochem. Pharmacol.7,1806–1813 (2009).CrossrefGoogle Scholar
    • 54  Lee CH, Kim EY, Jeon K et al. Simple, efficient, and reproducible gene transfection of mouse embryonic stem cells by Magnetofection. Stem Cells Dev.17,133–141 (2008).Crossref, Medline, CASGoogle Scholar
    • 55  Melki MT, Saïdi H, Dufour A, Olivo-Marin JC, Gougeon ML. Escape of HIV-1-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross-talk – a pivotal role of HMGB1. PLoS Pathog.6,E10000862 (2010).CrossrefGoogle Scholar
    • 56  Khurana S, Jaiswal AK, Mukhopadhyay A. Hepatocyte nuclear factor-4a induces transdifferentiation of hematopoietic cells into hepatocytes. J. Biol. Chem.285,4725–4731 (2010).Crossref, Medline, CASGoogle Scholar
    • 57  Fallini C, Bassell GJ, Rossoll W. High-efficiency transfection of cultured primary motor neurons to study protein localization, trafficking, and function. Molecular Neurodegeneration5,17 (2010).▪ Provides a highly efficient protocol for motor neuron transfection by Magnetofection™.Crossref, MedlineGoogle Scholar
    • 58  Krotz F, Sohn HY, Gloe T, Plank C, Pohl U. Magnetofection potentiates gene delivery to cultured endothelial cells. J. Vasc. Res.40,425–434 (2003).Crossref, MedlineGoogle Scholar
    • 59  Sapet C, Simoncini S, Loriod B et al. Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2. Blood108(6),1868–1876 (2006).Crossref, Medline, CASGoogle Scholar
    • 60  Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific interference by double-stranded RNA in Caenorhabditis elegans. Nature391,806–811 (1998).Crossref, Medline, CASGoogle Scholar
    • 61  de Fougerolles A, Vornlocher HP, Maraganore J, Lieberman J. Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug. Discov.6,443–453 (2007).Crossref, Medline, CASGoogle Scholar
    • 62  Kim DH, Rossi JJ. RNAi mechanisms and applications. Biotechniques44,613–616 (2008).Crossref, Medline, CASGoogle Scholar
    • 63  Mykhaylyk O, Zelphati O, Rosenecker J, Plank C. siRNA delivery by Magnetofection. Curr. Opin. Mol. Ther.10,493–505 (2008).▪ Comprehensive review on siRNA delivery by Magnetofection.Medline, CASGoogle Scholar
    • 64  Mykhaylyk O, Zelphati O, Hammerschmid E, Anton M, Rosenecker J, Plank C. Recent advances in Magnetofection and its potential to deliver siRNAs in vitro. Meth. Mol. Biol.487,111–146 (2009).Crossref, Medline, CASGoogle Scholar
    • 65  McCaig C, Duval C, Hemers E et al. The role of matrix metalloproteinase-7 in redefining the gastric microenvironment in response to Helicobacter pylori. Gastroenterology130,1754–1763 (2006).Crossref, Medline, CASGoogle Scholar
    • 66  Ensenauer R, Hartl D, Vockley J, Roscher AA, Fuchs U. Efficient and gentle siRNA delivery by magnetofection. Biotech. Histochem. DOI:10.319/10520291003675485 (2010) (Epub ahead of print).MedlineGoogle Scholar
    • 67  Krotz F, de Wit C, Sohn HY et al. Magnetofection – a highly efficient tool for antisense oligonucleotide delivery in vitro and in vivo. Mol. Ther.7,700–710 (2003).Crossref, Medline, CASGoogle Scholar
    • 68  Naka K, Hoshii T, Muraguchi T et al. TGF-β-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature463,676–680 (2010).Crossref, Medline, CASGoogle Scholar
    • 69  Sacha JB, Reynolds MR, Buechler MB et al. Differential antigen presentation kinetics of CD8+ T-cell epitopes derived from the same viral protein. J. Virol.82(18),9293–9298 (2008).Crossref, Medline, CASGoogle Scholar
    • 70  Gliddon BL, Nguyen NV, Gunn PA, Gleeson PA, van Driel IR. Isolation, culture and adenoviral transduction of parietal cells from mouse gastric mucosa. Biomed. Mater.3(3),034117 (2008).CrossrefGoogle Scholar
    • 71  Orlando C, Castellani S, Mykhaylyk O et al. Magnetically guided lentiviral-mediated transduction of airway epithelial cells. J. Gene Med.12,747–754 (2010).Crossref, Medline, CASGoogle Scholar
    • 72  Sacha JB, Giraldo-Vela JP, Buechler MB et al. Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. Proc. Natl Acad. Sci. USA106(24),9791–9796 (2009).Crossref, Medline, CASGoogle Scholar
    • 73  Payne RP, Kloverpris H, Sacha JB et al. Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B*2705-restricted CD8+ T-cells. J. Virol.84(20),10543–10557 (2010).Crossref, Medline, CASGoogle Scholar
    • 74  Kadota SI, Kanayama T, Miyajima N, Takeuchi K, Nagata K. Enhancing of measles virus infection by Magnetofection. J. Virol. Meth.128(1–2),61–66 (2005).Crossref, Medline, CASGoogle Scholar
    • 75  Plank C, Anton M, Rudolph C, Rosenecker J, Krotz F. Enhancing and targeting nucleic acid delivery by magnetic force. Expert. Opin. Biol Ther.3,745–758 (2003).Crossref, Medline, CASGoogle Scholar
    • 76  Jahnke A, Hirschberger J, Fischer C et al. Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using Magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a Phase-I study. J. Vet. Med. A Physiol. Pathol. Clin. Med.54,599–606 (2007).▪ Demonstrates the potential of in vivo Magnetofection for the treatment of fibrosarcomas.Crossref, Medline, CASGoogle Scholar
    • 77  Huttinger C, Hirschberger J, Jahnke A et al. Neoadjuvant gene delivery of feline granulocyte–macrophage colony-stimulating factor using Magnetofection for the treatment of feline fibrosarcomas: a Phase I trial. J. Gene Med.10,655–667 (2008).▪ Phase I clinical trial for the treatment of fibrosarcoma using Magnetofection.Crossref, MedlineGoogle Scholar
    • 78  Dames P, Gleich B, Flemmer A et al. Targeted delivery of magnetic aerosol droplets to the lung. Nat. Nanotechnol.2(8),495–499 (2007).Crossref, MedlineGoogle Scholar
    • 79  Xenariou S, Griesenbach U, Ferrari S et al. Using magnetic forces to enhance non-viral gene transfer to airway epithelium in vivo. Gene Therapy13,1545–1552 (2006).Crossref, Medline, CASGoogle Scholar
    • 80  Namiki Y, Namiki T, Yoshida H et al. A novel magnetic crystal-lipid nanostructure for magnetically guided in vivo gene delivery. Nat. Nanotechnol.4(9),598–606 (2009).Crossref, Medline, CASGoogle Scholar
    • 81  Hofmann A, Wenzel D, Becher UM et al. Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles. Proc. Natl Acad. Sci. USA106(1),44–49 (2009).Crossref, Medline, CASGoogle Scholar
    • 82  Nel AE, Madler L, Velegol D et al. Understanding biophysicochemical interactions at the nano-bio interface. Nat. Mater.8(7),543–557 (2009).Crossref, Medline, CASGoogle Scholar
    • 83  Papanikolaou G, Pantopoulos K. Iron metabolism and toxicity. Toxicol. Appl. Pharmacol.202,199–211 (2005).Crossref, Medline, CASGoogle Scholar
    • 84  Thorek DLJ, Chen AK, Czupryna J, Tsourkas A. Superparamagnetic iron oxide nanoparticle probes for molecular imaging. Ann. Biomed. Engineer.34(1),23–38 (2006).Crossref, MedlineGoogle Scholar
    • 85  Shubayev VI, Pisanic TR, Jin S. Magnetic nanoparticles for theragnostics. Adv. Drug Deliv. Rev.61(6),467–477 (2009).Crossref, Medline, CASGoogle Scholar
    • 86  Weissleder R, Bogdanov A, Neuwelt EA, Papisov M. Long-circulating iron oxides for MR imaging. Adv. Drug Deliv. Rev.16(2),321–334 (1995).Crossref, CASGoogle Scholar
    • 87  Gupta AK, Naregalkar RR, Vaidya VD, Gupta M. Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications. Nanomed.2(1),23–39 (2007).Crossref, Medline, CASGoogle Scholar
    • 88  Jain TK, Reddy MK, Morales MA, Leslie-Pelecky DL, Labhasetwar V. Biodistribution, clearance and biocompatibility of iron oxide magnetic nanoparticles in rats. Mol. Pharmaceutics5(2),316–327 (2008).Crossref, Medline, CASGoogle Scholar
    • 89  Pisanic II TR, Blackwell JD, Shubayev VI, Finones RR, Jin S. Nanotoxicity of iron oxide nanoparticle internalization in growing neurons. Biomaterials28(16),2572–2581 (2007).Crossref, MedlineGoogle Scholar
    • 90  Apopa PL, Qian Y, Shao R et al. Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling. Part Fibre Toxicol.6,1 (2009).Crossref, MedlineGoogle Scholar
    • 91  Soenen SJH, Nuytten N, De Meyer SF, De Smedt SC, De Cuyper M. High intracellular iron oxide nanoparticle concentrations affect cellular cytoskeleton and focal adhesion kinase-mediated signaling. Small6(7),832–842 (2010).Crossref, Medline, CASGoogle Scholar
    • 92  Soenen SJH, Himmelreich U, Nuytten N, De Cuyper M. Cytotoxic effects of iron oxide nanoparticles and implications for safety in cell labelling. Biomaterials32(1),195–205 (2011).Crossref, Medline, CASGoogle Scholar
    • 93  Schwert DD, Davies JA, Richardson N. Non-gadolinium-based MRI contrast agents. Top. Curr. Chem.221,165–1999 (2002).Crossref, CASGoogle Scholar
    • 94  Zborowski M. Commercial magnetic cell separation instruments and reagents. In: Laboratory Techniques in Biochemistry and Molecular Biology. Zborowski M, Chalmers JJ (Eds). Elsevier BV, Oxford, UK 32, 265–292 (2007).Google Scholar
    • 95  Guo X, Szoka FC Jr. Chemical approaches to triggerable lipid vesicles for drug and gene delivery. Acc. Chem. Res.36,335–341 (2003).Crossref, Medline, CASGoogle Scholar
    • 96  Forrest ML, Koerber JT, Pack DW. A degradable polyethyleneimine derivative with low toxicity for highly efficient gene delivery. Bioconjugate Chem.14,934–940 (2003).Crossref, Medline, CASGoogle Scholar
    • 97  Pathak A, Patnaik S, Gupta KC. Recent trends in non-viral vector-mediated gene delivery. Biotechnol. J.4(11),1559–1572 (2009).Crossref, Medline, CASGoogle Scholar
    • 98  Yang F, Green JJ, Dinio T et al. Gene delivery to human adult and embryonic cell-derived stem cells using biodegradable nanoparticulate polymeric vectors. Gene Ther.16,533–546 (2009).Crossref, Medline, CASGoogle Scholar
    • 99  Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials26,3995–4021 (2005).Crossref, Medline, CASGoogle Scholar
    • 100  Lu AH, Salabas EL, Schüth F. Magnetic nanoparticles: synthesis, protection, functionalization, and application. Angew. Chem. Int. Ed.46,1222–1244 (2007).Crossref, Medline, CASGoogle Scholar
    • 101  Laurent S, Forge D, Port M et al. Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev.108,2064–2110 (2008).▪▪ Extensively reviews the different procedures for MNP synthesis and characterization.Crossref, Medline, CASGoogle Scholar
    • 102  Pfeifer C, Himmel A, Geiger JP, Aneja MK, Rudolph C. Efficient, specific and targeted delivery of genes to the lungs. Therapeut. Deliv.1,133–148 (2010).Link, CASGoogle Scholar
    • 103  Hafeli UO, Aue J, Damani J. The biocompatibility and toxicity of magnetic particles. In: Laboratory Techniques in Biochemistry and Molecular Biology. Zborowski M, Chalmers JJ (Eds). Elsevier BV, Oxford, UK 32, 163–223 (2007).▪ Reviews the MNP characteristics influencing toxicity and the different toxicity tests in vitro and in vivo.Google Scholar
    • 104  Lee J, Isobe T, Senna M. Preparation of ultrafine Fe3O4 particles by precipitation in the presence of PVA at high pH. J. Colloid Interface Sci.177(2),490–494 (1996)Crossref, CASGoogle Scholar
    • 105  Mykhaylyk O, Matoussevitch N, Bonnemann H, Plank C. Cobalt versus magnetite nanoparticles: cell toxicity and efficiency as components of gene delivery vectors in vitro. 11th International Conference on Magnetic Fluids. Košice, Slovakia 23–27 July 2007 (Abstract 8P10).Google Scholar
    • 106  Voltairas PA, Fotiadis DI, Michailis LK. Hydrodynamics of magnetic drug targeting. J. Biomech.35(6),813–821 (2002).Crossref, Medline, CASGoogle Scholar
    • 107  Alexiou C, Diehl D, Henninger P et al. A high field gradient magnet for magnetic drug targeting. IEEE Trans. Appl. Supercond.16(2),1527–1530 (2006).CrossrefGoogle Scholar
    • 108  Babincova M, Babinec C, Bergemann C. High-gradient magnetic capture of ferrofluids: implications for drug targeting and tumor embolization. Z. Naturforsch C56(9–10),909–911 (2001).Crossref, Medline, CASGoogle Scholar
    • 109  Yellen BB, Forbes ZG, Halverson DS et al. Targeted drug delivery to magnetic implants for therapeutic application. J. Magn. Magn. Mater.293(1),647–654.CrossrefGoogle Scholar
    • 110  Eder P, Probst D, Rosker C et al. Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex. Cardiovasc. Res.73(1),111–119 (2007).Crossref, Medline, CASGoogle Scholar
    • 111  Deleuze V, Chalhoub E, El-Hajj R et al. TAL-1/SCL and its partners E47 and LMO2 up-regulate VE-cadherin expression in endothelial cells. Mol. Cell. Biol.27(7),2687–2697 (2007).Crossref, Medline, CASGoogle Scholar
    • 112  Simoncini S, Njock MS, Robert S et al. TRAIL/Apo2L mediates the release of procoagulant endothelial microparticles induced by thrombin in vitro. Circ. Res.104,943–951 (2009).Crossref, Medline, CASGoogle Scholar
    • 113  Sacha JB, Chung C, Rakasz EG et al. Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression. J. Immunol.178,2746–2754 (2007).Crossref, Medline, CASGoogle Scholar
    • 114  Minang JT, Trivett MT, Coren LV et al. The Mamu B*17-restricted SIV Nef IW9 to TW9 mutation abrogates correct epitope processing and presentation without loss of replicative fitness. Virology375(1),307–314 (2008).Crossref, Medline, CASGoogle Scholar
    • 115  Ge X, Low B, Liang M, Fu J. Angiotensin II directly triggers endothelial exocytosis via protein kinase C-dependent protein kinase D2 activation. J. Pharmacol. Sci.105,168–176 (2007).Crossref, Medline, CASGoogle Scholar
    • 116  Mizuhara E, Minaki Y, Nakatani T et al. Purkinje cells originate from cerebellar ventricular zone progenitors positive for Neph3 and E-cadherin. Dev. Biol.338(2),202–214 (2010).Crossref, Medline, CASGoogle Scholar
    • 117  Minami R, Yamamoto M, Takahama S et al. RCAS1 induced by HIV-Tat is involved in the apoptosis of HIV-1 infected and uninfected CD4+ T cells. Cell. Immunol.243(1),41–47 (2006).Crossref, Medline, CASGoogle Scholar
    • 118  Pickard M, Chari D. Enhancement of magnetic nanoparticles-mediated gene transfer to astrocytes by ‘Magnetofection’: effects of static and oscillating fields. Nanomed.5(2),217–232 (2010).Crossref, Medline, CASGoogle Scholar
    • 119  Burdof L, Schuhmann N, Postrach J et al. AAV-mediated gene transfer to cardiac cells in a heterotopic rat heart transplantation model. Transplant. Proc.39(2),567–568 (2007).Crossref, MedlineGoogle Scholar
    • 120  Svingen T, Wilhelm D, Combes AN et al. Ex vivo magnetofection: a novel strategy for the study of the gene function in mouse organogenesis. Dev. Dyn.238(4),956–964 (2009).Crossref, Medline, CASGoogle Scholar
    • 121  Holzbach T, Vlaskou D, Neshkova I et al. Non-viral VEGF165 gene therapy – Magnetofection of acoustically active magnetic lipospheres (‘magnetobubbles’) increases tissue survival in an oversized skin flap model. J. Cell. Mol. Med.14(3),587–599 (2010).Medline, CASGoogle Scholar
    • 122  Wang X, Mani P, Sarkar DP, Roy-Chowdhury N, Roy-Chowdhury J. Ex vivo gene transfer into hepatocytes. Meth. Mol. Biol.481,1–23 (2009).Crossref, MedlineGoogle Scholar
    • 201  Plank C, Bergemann C: WO02/000870 (2002).Google Scholar
    • 301  John Wiley & Sons, 2007. www.wiley.co.uk/genetherapy/clinicalGoogle Scholar