Covalently bonded dendrimer-maghemite nanosystems: nonviral vectors for in vitrogene magnetofection

In this work novel nonviral nanosystems for in vitrogene magnetofection are presented. The multifunctional vectors consist of superparamagnetic iron oxide nanoparticles functionalized with low generations of poly(propyleneimine) dendrimers. The dendrimers are attached to the iron oxide nanoparticles through covalent bonds via a one-pot sol–gel synthetic route. This approach allows a direct dendritic decoration of the iron oxide NPs without any additional surface modification. Furthermore, this strategy avoids the multistep procedures of dendritic growth onto solid surfaces. The core–shell hybrid structures are water soluble as colloidal ferrofluids which are long-term stable at physiological pH. In vitro transfection experiments were assayed with Saos-2 osteoblasts, using as reporter gene a plasmid DNA that codes for the green fluorescent protein. Gene delivery experiments were carried out in the presence and in the absence of a magnetic field. The transfection efficiency strongly depends on the presence of the magnetic field and the dendrimer generation. The covalent bonding between the dendrimers and the magnetic nanoparticles surface ensures the vector integrity throughout storage and application. The nanosystems couple the DNA fragments and safely transport them under magnetic stimulus from the extracellular environment to the interior of the cell.

[1]  Donald A Tomalia,et al.  Dendrimers in biomedical applications--reflections on the field. , 2005, Advanced drug delivery reviews.

[2]  M. Muthukumar,et al.  Tuning the Density Profile of Dendritic Polyelectrolytes , 1998 .

[3]  É. Boisselier,et al.  Dendrimers designed for functions: from physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine. , 2010, Chemical reviews.

[4]  M. Drofenik,et al.  Functionalization of magnetic nanoparticles with 3-aminopropyl silane , 2009 .

[5]  D. Kohn,et al.  Analysis of Novel Nonviral Gene Transfer Systems for Gene Delivery to Cells of the Musculoskeletal System , 2008, Molecular biotechnology.

[6]  A. Schätzlein,et al.  Dendrimers in gene delivery. , 2005, Advanced drug delivery reviews.

[7]  Su He Wang,et al.  Dendrimer‐Functionalized Iron Oxide Nanoparticles for Specific Targeting and Imaging of Cancer Cells , 2007 .

[8]  H. Hofmann,et al.  Characterization of PEI-coated superparamagnetic iron oxide nanoparticles for transfection: Size distribution, colloidal properties and DNA interaction , 2007 .

[9]  In-Kyu Park,et al.  Hybrid superparamagnetic iron oxide nanoparticle-branched polyethylenimine magnetoplexes for gene transfection of vascular endothelial cells. , 2010, Biomaterials.

[10]  Jeff W. M. Bulte,et al.  Synthesis and Characterization of Soluble Iron Oxide−Dendrimer Composites , 2001 .

[11]  H. Alper,et al.  Metal supported on dendronized magnetic nanoparticles: highly selective hydroformylation catalysts. , 2006, Journal of the American Chemical Society.

[12]  Chad A. Mirkin,et al.  Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation , 2006, Science.

[13]  Jay Neitz,et al.  Gene therapy for red-green colour blindness in adult primates , 2009, Nature.

[14]  R. Massart,et al.  Preparation of aqueous magnetic liquids in alkaline and acidic media , 1981 .

[15]  C. Pichot,et al.  Preparation and characterization of narrow sized (o/w) magnetic emulsion , 2002 .

[16]  J. Dennig,et al.  Gene transfer into eukaryotic cells using activated polyamidoamine dendrimers. , 2002, Journal of biotechnology.

[17]  C. Ozkan,et al.  Dendrimer-modified magnetic nanoparticles enhance efficiency of gene delivery system. , 2007, Cancer research.

[18]  W. Stöber,et al.  Controlled growth of monodisperse silica spheres in the micron size range , 1968 .

[19]  Xuefei Huang,et al.  Functionalization of magnetic nanoparticles with organic molecules: loading level determination and evaluation of linker length effect on immobilization. , 2008, Chirality.

[20]  P. Dumas,et al.  Organosilane-modified maghemite nanoparticles and their use as co-initiator in the ring-opening polymerization of ɛ-caprolactone , 2005 .

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

[22]  E. W. Meijer,et al.  About Dendrimers: Structure, Physical Properties, and Applications. , 1999, Chemical reviews.

[23]  Thommey P. Thomas,et al.  Synthesis, characterization, and intracellular uptake of carboxyl-terminated poly(amidoamine) dendrimer-stabilized iron oxide nanoparticles. , 2007, Physical chemistry chemical physics : PCCP.

[24]  M. Vallet‐Regí,et al.  A novel synthetic strategy for covalently bonding dendrimers to ordered mesoporous silica: potential drug delivery applications , 2009 .

[25]  Huixin He,et al.  Labile catalytic packaging of DNA/siRNA: control of gold nanoparticles "out" of DNA/siRNA complexes. , 2010, ACS nano.

[26]  Matthias Epple,et al.  Inorganic nanoparticles as carriers of nucleic acids into cells. , 2008, Angewandte Chemie.

[27]  Su He Wang,et al.  Dendrimer‐Functionalized Shell‐crosslinked Iron Oxide Nanoparticles for In‐Vivo Magnetic Resonance Imaging of Tumors , 2008 .

[28]  E. Snoeck,et al.  Surface effects in maghemite nanoparticles , 2007 .

[29]  Saji George,et al.  Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs. , 2009, ACS nano.

[30]  J Henke,et al.  Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo , 2002, Gene Therapy.

[31]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[32]  M. Vallet‐Regí,et al.  Aerosol-assisted synthesis of magnetic mesoporous silica spheres for drug targeting , 2007 .

[33]  Carlos Rinaldi,et al.  Water dispersible iron oxide nanoparticles coated with covalently linked chitosan , 2009 .

[34]  William A. Goddard,et al.  Starburst Dendrimers: Molecular‐Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter , 1990 .

[35]  Victor S-Y Lin,et al.  A polyamidoamine dendrimer-capped mesoporous silica nanosphere-based gene transfection reagent. , 2004, Journal of the American Chemical Society.

[36]  R. Amal,et al.  Assembly of polyethylenimine-based magnetic iron oxide vectors: insights into gene delivery. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[37]  Peter van Gelderen,et al.  Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells , 2001, Nature Biotechnology.

[38]  Narendra Kumar Jain,et al.  Dendrimers in oncology: an expanding horizon. , 2009, Chemical reviews.

[39]  G. Lukács,et al.  Intracellular routing of plasmid DNA during non-viral gene transfer. , 2005, Advanced drug delivery reviews.

[40]  Meredith A Mintzer,et al.  Nonviral vectors for gene delivery. , 2009, Chemical reviews.

[41]  Ijeoma F. Uchegbu,et al.  The Lower-Generation Polypropylenimine Dendrimers Are Effective Gene-Transfer Agents , 2002, Pharmaceutical Research.

[42]  Hsin‐Lung Chen,et al.  Effects of the nanostructure of dendrimer/DNA complexes on their endocytosis and gene expression. , 2010, Biomaterials.

[43]  S K Libutti,et al.  Progress in antiangiogenic gene therapy of cancer , 2000, Cancer.