Self-assembled magnetic theranostic nanoparticles for highly sensitive MRI of minicircle DNA delivery.

As a versatile gene vector, minicircle DNA (mcDNA) has a great potential for gene therapy. However, some serious challenges remain, such as to effectively deliver mcDNA into targeted cells/tissues and to non-invasively monitor the delivery of the mcDNA. Superparamagnetic iron oxide (SPIO) nanoparticles have been extensively used for both drug/gene delivery and diagnosis. In this study, an MRI visible gene delivery system was developed with a core of SPIO nanocrystals and a shell of biodegradable stearic acid-modified low molecular weight polyethyleneimine (Stearic-LWPEI) via self-assembly. The Stearic-LWPEI-SPIO nanoparticles possess a controlled clustering structure, narrow size distribution and ultrasensitive imaging capacity. Furthermore, the nanoparticle can effectively bind with mcDNA and protect it from enzymatic degradation. In conclusion, the nanoparticle shows synergistic advantages in the effective transfection of mcDNA and non-invasive MRI of gene delivery.

[1]  Z. Gu,et al.  N-alkyl-polyethylenimine stabilized iron oxide nanoparticles as MRI visible transfection agents. , 2012, Journal of nanoscience and nanotechnology.

[2]  B. Liu,et al.  Bacterial magnetic particles as a novel and efficient gene vaccine delivery system , 2011, Gene Therapy.

[3]  Guofeng Zhang,et al.  Functional MnO nanoclusters for efficient siRNA delivery. , 2011, Chemical communications.

[4]  Hua Ai,et al.  N-Alkyl-PEI-functionalized iron oxide nanoclusters for efficient siRNA delivery. , 2011, Small.

[5]  Rui Peng,et al.  Lipoic acid modified low molecular weight polyethylenimine mediates nontoxic and highly potent in vitro gene transfection. , 2011, Molecular pharmaceutics.

[6]  Hua Ai Layer-by-layer capsules for magnetic resonance imaging and drug delivery. , 2011, Advanced drug delivery reviews.

[7]  Hua Ai,et al.  Surface-engineered magnetic nanoparticle platforms for cancer imaging and therapy. , 2011, Accounts of chemical research.

[8]  Miqin Zhang,et al.  pH-Sensitive siRNA nanovector for targeted gene silencing and cytotoxic effect in cancer cells. , 2010, Molecular pharmaceutics.

[9]  M. Kay,et al.  A Simple And Rapid Minicircle DNA Vector Manufacturing System , 2010, Nature Biotechnology.

[10]  R. Amal,et al.  Polyethylenimine based magnetic iron-oxide vector: the effect of vector component assembly on cellular entry mechanism, intracellular localization, and cellular viability. , 2010, Biomacromolecules.

[11]  Yu-cheng Tseng,et al.  Biodegradable calcium phosphate nanoparticle with lipid coating for systemic siRNA delivery. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[12]  Orawan Suwantong,et al.  Aliphatic lipid substitution on 2 kDa polyethylenimine improves plasmid delivery and transgene expression. , 2009, Molecular pharmaceutics.

[13]  M. Kay,et al.  Novel Minicircle Vector for Gene Therapy in Murine Myocardial Infarction , 2009, Circulation.

[14]  Hua Ai,et al.  Manganese ferrite nanoparticle micellar nanocomposites as MRI contrast agent for liver imaging. , 2009, Biomaterials.

[15]  Jinming Gao,et al.  MRI-visible polymeric vector bearing CD3 single chain antibody for gene delivery to T cells for immunosuppression. , 2009, Biomaterials.

[16]  Stephanie E. A. Gratton,et al.  The effect of particle design on cellular internalization pathways , 2008, Proceedings of the National Academy of Sciences.

[17]  Jinwoo Cheon,et al.  Chemical design of nanoparticle probes for high-performance magnetic resonance imaging. , 2008, Angewandte Chemie.

[18]  C. Yuan,et al.  Determination of nanoparticle vehicle unpackaging by MR imaging of a T(2) magnetic relaxation switch. , 2008, Biomaterials.

[19]  Jo Wixon,et al.  Gene therapy clinical trials worldwide to 2007—an update , 2007, The journal of gene medicine.

[20]  W. Jechlinger Optimization and delivery of plasmid DNA for vaccination , 2006, Expert review of vaccines.

[21]  L. Bonetta The inside scoop—evaluating gene delivery methods , 2005, Nature Methods.

[22]  J. Duerk,et al.  Magnetite‐Loaded Polymeric Micelles as Ultrasensitive Magnetic‐Resonance Probes , 2005 .

[23]  Jinwoo Cheon,et al.  Surface modulation of magnetic nanocrystals in the development of highly efficient magnetic resonance probes for intracellular labeling. , 2005, Journal of the American Chemical Society.

[24]  Daniel W. Pack,et al.  Design and development of polymers for gene delivery , 2005, Nature Reviews Drug Discovery.

[25]  Cyril Aymonier,et al.  Core-Shell-Structured Highly Branched Poly(ethylenimine amide)s: Synthesis and Structure , 2005 .

[26]  R. Müller,et al.  Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[27]  Hao Zeng,et al.  Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles. , 2004, Journal of the American Chemical Society.

[28]  M. Kay,et al.  Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[29]  X. Shuai,et al.  Novel Biodegradable Ternary Copolymers hy-PEI-g-PCL-b-PEG: Synthesis, Characterization, and Potential as Efficient Nonviral Gene Delivery Vectors , 2003 .

[30]  S. Gambhir,et al.  Molecular imaging in living subjects: seeing fundamental biological processes in a new light. , 2003, Genes & development.

[31]  R. Blasberg Imaging Gene Expression and Endogenous Molecular Processes: Molecular Imaging , 2002, Journal of Cerebral Blood Flow and Metabolism.

[32]  Duane D. Miller,et al.  Novel branched poly(ethylenimine)-cholesterol water-soluble lipopolymers for gene delivery. , 2002, Biomacromolecules.

[33]  E. Wagner,et al.  Design and gene delivery activity of modified polyethylenimines. , 2001, Advanced drug delivery reviews.

[34]  D W Pack,et al.  Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[35]  M. Nango,et al.  Polycation liposomes, a novel nonviral gene transfer system, constructed from cetylated polyethylenimine , 2000, Gene Therapy.

[36]  R. Weissleder Molecular imaging: exploring the next frontier. , 1999, Radiology.

[37]  A. Mikos,et al.  Poly(ethylenimine) and its role in gene delivery. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[38]  Katsuhiko Ariga,et al.  Alternate Assembly of Ordered Multilayers of SiO2 and Other Nanoparticles and Polyions , 1997 .

[39]  D. Scherman,et al.  A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[40]  A. Miller,et al.  Human gene therapy comes of age , 1992, Nature.

[41]  G. Pietersz The linkage of cytotoxic drugs to monoclonal antibodies for the treatment of cancer. , 1990, Bioconjugate chemistry.

[42]  Xiaoyuan Chen,et al.  Design and fabrication of N-alkyl-polyethylenimine-stabilized iron oxide nanoclusters for gene delivery. , 2012, Methods in enzymology.

[43]  T. Park,et al.  Surface functionalized hollow manganese oxide nanoparticles for cancer targeted siRNA delivery and magnetic resonance imaging. , 2011, Biomaterials.

[44]  Fabao Gao,et al.  Low molecular weight alkyl-polycation wrapped magnetite nanoparticle clusters as MRI probes for stem cell labeling and in vivo imaging. , 2011, Biomaterials.

[45]  Z. Gu,et al.  Self-assembly of magnetite nanocrystals with amphiphilic polyethylenimine: structures and applications in magnetic resonance imaging. , 2009, Journal of nanoscience and nanotechnology.

[46]  Xuesi Chen,et al.  Gene transfection of hyperbranched PEI grafted by hydrophobic amino acid segment PBLG. , 2007, Biomaterials.

[47]  M. Glodde,et al.  Physiochemical properties of low and high molecular weight poly(ethylene glycol)-grafted poly(ethylene imine) copolymers and their complexes with oligonucleotides. , 2006, Biomacromolecules.

[48]  K. Kono,et al.  Transfection activity of polyamidoamine dendrimers having hydrophobic amino acid residues in the periphery. , 2005, Bioconjugate chemistry.