Abstract
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
- 1 Kohn DB, Candotti F. Gene therapy fulfilling its promise. N. Engl. J. Med.360(5),518–521 (2009).Crossref, Medline, CAS, Google Scholar
- 2 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, CAS, Google Scholar
- 3 Williams DA. Gene therapy continues to mature and face challenges. Mol. Ther.17(8),1305–1306 (2009).Crossref, Medline, CAS, Google Scholar
- 4 Aiuti A, Roncarolo MG. Ten years of gene therapy for primary immune deficiencies. Hematology2009,682–689 (2009).Crossref, Google Scholar
- 5 Zallen DT. US gene therapy in crisis. Trends Genet.16,272–275 (2000).Crossref, Medline, Google Scholar
- 6 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, CAS, Google Scholar
- 7 Kostarelos K, Miller AD. What role can chemistry play in cationic liposome-based gene therapy research today? Adv. Genet.53,69–118 (2005).Crossref, Google Scholar
- 8 Li W, Szoka Jr FC. Lipid-based nanoparticles for nucleic acid delivery. Pharm. Res.24,438–449 (2007).Crossref, Medline, Google Scholar
- 9 Mintzer MA, Simanek EE. Nonviral vectors for gene delivery. Chem. Rev.109,259–302 (2009).▪ Comprehensive review on lipid-based gene delivery.Crossref, Medline, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google Scholar
- 13 Woodle MC, Lasic DD. Sterically stabilized liposomes. Biochim. Biophys. Acta1113,171–199 (1992).Crossref, Medline, CAS, Google Scholar
- 14 Deonarain MP. Ligand-targeted receptor-mediated vectors for gene delivery. Exp. Opin. Ther. Patents8(1),53–69 (1998).Crossref, CAS, Google 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).CAS, Google 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, CAS, Google 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, CAS, Google Scholar
- 19 Arruebo M, Fernandez-Pacheco R, Ibarra MR, Santamaria J. Magnetic nanoparticles for drug delivery. Nano Today2,22–32 (2007).Crossref, Google 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).Crossref, Google 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, CAS, Google 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, CAS, Google 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, Medline, Google 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, Medline, Google Scholar
- 25 Massart R. Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Trans. Magn.17(2),1247–1248 (1981).Crossref, Google 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, CAS, Google Scholar
- 27 Albornoz C, Jacobo SE. Preparation of biocompatible magnetic film from aqueous ferrofluid. J. Magn. Magn. Mater.305(1),12–15 (2006).Crossref, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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).CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, Medline, Google Scholar
- 38 Zelphati O, Szoka FC Jr. Mechanism of oligonucleotide release from cationic liposomes. Proc. Natl Acad. Sci. USA93,11493–11498 (1996).Crossref, Medline, CAS, Google 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, CAS, Google 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, CAS, Google Scholar
- 41 Bulte JWM, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed.17,484–499 (2004).Crossref, Medline, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google Scholar
- 45 Dean DA, Strong DD, Zimmer WE. Nuclear entry of non viral vectors. Gene Ther.12,881–890 (2005).Crossref, Medline, CAS, Google Scholar
- 46 Melchior F, Gerace L. Mechanisms of nuclear protein import. Curr. Opin. Cell. Biol.7,310–318 (1995).Crossref, Medline, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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).Crossref, Google 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, CAS, Google 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, CAS, Google 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).Crossref, Google 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, CAS, Google 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).Crossref, Google 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, CAS, Google 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, Medline, Google 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, Medline, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google Scholar
- 62 Kim DH, Rossi JJ. RNAi mechanisms and applications. Biotechniques44,613–616 (2008).Crossref, Medline, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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).Medline, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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).Crossref, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, Medline, Google 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, Medline, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google Scholar
- 83 Papanikolaou G, Pantopoulos K. Iron metabolism and toxicity. Toxicol. Appl. Pharmacol.202,199–211 (2005).Crossref, Medline, CAS, Google 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, Medline, Google Scholar
- 85 Shubayev VI, Pisanic TR, Jin S. Magnetic nanoparticles for theragnostics. Adv. Drug Deliv. Rev.61(6),467–477 (2009).Crossref, Medline, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, Medline, Google 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, Medline, Google 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, CAS, Google 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, CAS, Google Scholar
- 93 Schwert DD, Davies JA, Richardson N. Non-gadolinium-based MRI contrast agents. Top. Curr. Chem.221,165–1999 (2002).Crossref, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google Scholar
- 99 Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials26,3995–4021 (2005).Crossref, Medline, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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).Crossref, Google 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, CAS, Google 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.Crossref, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, CAS, Google 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, Medline, Google 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, CAS, Google 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, CAS, Google 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, Medline, Google Scholar
- 201 Plank C, Bergemann C: WO02/000870 (2002).Google Scholar
- 301 John Wiley & Sons, 2007. www.wiley.co.uk/genetherapy/clinicalGoogle Scholar
