Nanoparticles as Nonviral Gene Delivery Vectors

Gene therapy, as therapeutic treatment to genetic or acquired diseases, is attracting much interest in the research community, leading to noteworthy developments over the past two decades. Although this field is still dominated by viral vectors, nonviral vectors have recently received an ever increasing attention in order to overcome the safety problems of their viral counterpart. This review presents the biological aspects involved in the gene delivery process and explores the recent developments and achievements of nonviral gene carriers.

[1]  S. C. O'brien,et al.  C60: Buckminsterfullerene , 1985, Nature.

[2]  T. Brill,et al.  Advances in magnetofection—magnetically guided nucleic acid delivery , 2005 .

[3]  William D. Richardson,et al.  A short amino acid sequence able to specify nuclear location , 1984, Cell.

[4]  H. Hofmann,et al.  Intraarticular application of superparamagnetic nanoparticles and their uptake by synovial membrane—an experimental study in sheep , 2005 .

[5]  M. Su,et al.  Preparation of Fluorescent Silica Nanotubes and Their Application in Gene Delivery , 2005 .

[6]  C. Feldherr,et al.  Signal-mediated nuclear transport in proliferating and growth-arrested BALB/c 3T3 cells , 1991, The Journal of cell biology.

[7]  Nobuhiko Yui,et al.  Biocleavable Polyrotaxane−Plasmid DNA Polyplex for Enhanced Gene Delivery , 2006 .

[8]  Juan-Juan Xiang,et al.  IONP‐PLL: a novel non‐viral vector for efficient gene delivery , 2003, The journal of gene medicine.

[9]  L. C. Moore,et al.  Nuclear envelope permeability , 1975, Nature.

[10]  R. Lockey,et al.  Thiolated Chitosan/DNA Nanocomplexes Exhibit Enhanced and Sustained Gene Delivery , 2006, Pharmaceutical Research.

[11]  D. Scherman,et al.  Lipopolythioureas: a new non-cationic system for gene transfer. , 2007, Bioconjugate chemistry.

[12]  J. Kjems,et al.  The influence of polymeric properties on chitosan/siRNA nanoparticle formulation and gene silencing. , 2007, Biomaterials.

[13]  A. Maruyama,et al.  Biocleavable polyrotaxane-plasmid DNA polyplex for enhanced gene delivery. , 2006, Journal of the American Chemical Society.

[14]  V. Rotello,et al.  Inhibition of DNA transcription using cationic mixed monolayer protected gold clusters. , 2001, Journal of the American Chemical Society.

[15]  H. Mizuguchi,et al.  Nuclear targeting of DNA. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[16]  T. Reineke,et al.  Trehalose click polymers inhibit nanoparticle aggregation and promote pDNA delivery in serum. , 2006, Journal of the American Chemical Society.

[17]  Alexander M. Klibanov,et al.  Conjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Verkman,et al.  Actin Cytoskeleton as the Principal Determinant of Size-dependent DNA Mobility in Cytoplasm , 2005, Journal of Biological Chemistry.

[19]  Joseph Zabner,et al.  Cellular and Molecular Barriers to Gene Transfer by a Cationic Lipid (*) , 1995, The Journal of Biological Chemistry.

[20]  R. Langer,et al.  Exploring polyethylenimine‐mediated DNA transfection and the proton sponge hypothesis , 2005, The journal of gene medicine.

[21]  B. Steitz,et al.  Gene expression in synovial membrane cells after intraarticular delivery of plasmid-linked superparamagnetic iron oxide particles--a preliminary study in sheep. , 2006, Journal of nanoscience and nanotechnology.

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

[23]  V. Rotello,et al.  Controlled recovery of the transcription of nanoparticle-bound DNA by intracellular concentrations of glutathione. , 2005, Bioconjugate chemistry.

[24]  P. Noguchi Risks and benefits of gene therapy. , 2003, The New England journal of medicine.

[25]  B. Houk,et al.  Pharmacokinetics of Plasmid DNA in the Rat , 2004, Pharmaceutical Research.

[26]  Y. Mély,et al.  Physicochemical properties of low molecular weight alkylated chitosans: a new class of potential nonviral vectors for gene delivery. , 2006, Colloids and surfaces. B, Biointerfaces.

[27]  森下 紀夫,et al.  Magnetic nanoparticles with surface modification enhanced gene delivery of HVJ-E vector , 2006 .

[28]  J. Lehn,et al.  The design of cationic lipids for gene delivery. , 2005, Current pharmaceutical design.

[29]  R. Langer,et al.  Accelerated discovery of synthetic transfection vectors: parallel synthesis and screening of a degradable polymer library. , 2001, Journal of the American Chemical Society.

[30]  Jon Dobson,et al.  Improved method of recombinant AAV2 delivery for systemic targeted gene therapy. , 2002, Molecular therapy : the journal of the American Society of Gene Therapy.

[31]  M. Radosz,et al.  Biodegradable cationic polyester as an efficient carrier for gene delivery to neonatal cardiomyocytes , 2006, Biotechnology and bioengineering.

[32]  J. Rosenecker,et al.  Insights into the mechanism of magnetofection using PEI‐based magnetofectins for gene transfer , 2004, The journal of gene medicine.

[33]  Hepeng Jia Gene therapy finds welcoming environment in China , 2006, Nature Medicine.

[34]  M. Monsigny,et al.  Efficient gene transfer by histidylated polylysine/pDNA complexes. , 1999, Bioconjugate chemistry.

[35]  T. Lohman,et al.  Large electrostatic differences in the binding thermodynamics of a cationic peptide to oligomeric and polymeric DNA. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Daniel G. Anderson,et al.  Biodegradable polymeric vectors for gene delivery to human endothelial cells. , 2006, Bioconjugate chemistry.

[37]  Nan Wang,et al.  Construction, gene delivery, and expression of DNA tethered nanoparticles. , 2006, Molecular vision.

[38]  Andrew S. Mount,et al.  RNA polymer translocation with single-walled carbon nanotubes , 2004 .

[39]  M. Bassik,et al.  Nuclear import of DNA in digitonin-permeabilized cells. , 1997, Journal of cell science.

[40]  T. Niidome,et al.  Stabilizing of plasmid DNA in vivo by PEG-modified cationic gold nanoparticles and the gene expression assisted with electrical pulses. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[41]  D. Putnam,et al.  Design of imidazole-containing endosomolytic biopolymers for gene delivery. , 2000, Biotechnology and bioengineering.

[42]  D. Curiel,et al.  Efficient gene transfer to human endothelial cells using DNA complexed to adenovirus particles. , 1998, BioTechniques.

[43]  D. Escande,et al.  Polyethylenimine but Not Cationic Lipids Promotes Transgene Delivery to the Nucleus in Mammalian Cells* , 1998, The Journal of Biological Chemistry.

[44]  A S Verkman,et al.  Size-dependent DNA Mobility in Cytoplasm and Nucleus* , 2000, The Journal of Biological Chemistry.

[45]  E. Nabel,et al.  Transfection of human endothelial cells. , 1997, Cardiovascular research.

[46]  M. Bassik,et al.  DNA vector chemistry: The covalent attachment of signal peptides to plasmid DNA , 1998, Nature Biotechnology.

[47]  Tymish Y. Ohulchanskyy,et al.  Optical tracking of organically modified silica nanoparticles as DNA carriers: a nonviral, nanomedicine approach for gene delivery. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[48]  G. Felsenfeld,et al.  Deoxyribonucleic acid-polylysine complexes. Structure and nucleotide specificity. , 1969, Biochemistry.

[49]  T. Kissel,et al.  Integrin targeting using RGD‐PEI conjugates for in vitro gene transfer , 2003, The journal of gene medicine.

[50]  M. Prato,et al.  Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors. , 2005, Journal of the American Chemical Society.

[51]  M. Ogris,et al.  Adenovirus hexon protein enhances nuclear delivery and increases transgene expression of polyethylenimine/plasmid DNA vectors. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[52]  Daniel G. Anderson,et al.  Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery. , 2006, Journal of the American Chemical Society.

[53]  K. Mechtler,et al.  Transferrin-polycation-mediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[54]  D. Scherman,et al.  Design, synthesis, and evaluation of enhanced DNA binding new lipopolythioureas. , 2006, Bioconjugate chemistry.

[55]  G. Donofrio,et al.  A general synthesis of water soluble upper rim calix[n]arene guanidinium derivatives which bind to plasmid DNA , 2004 .

[56]  In Ho Song,et al.  In vitro and in vivo gene-transferring characteristics of novel cationic lipids, DMKD (O,O'-dimyristyl-N-lysyl aspartate) and DMKE (O,O'-dimyristyl-N-lysyl glutamate). , 2006 .

[57]  C. Feldherr,et al.  The location of the transport gate in the nuclear pore complex. , 1997, Journal of cell science.

[58]  C. Springer,et al.  Structure-activity relationship in cationic lipid mediated gene transfection. , 2003, Current medicinal chemistry.

[59]  G. Jia,et al.  Formulation and characterization of poly (d,l‐lactide‐co‐glycolide) nanoparticle containing vascular endothelial growth factor for gene delivery , 2006, Journal of clinical pharmacy and therapeutics.

[60]  J. C. Perales,et al.  Biochemical and Functional Characterization of DNA Complexes Capable of Targeting Genes to Hepatocytes via the Asialoglycoprotein Receptor* , 1997, The Journal of Biological Chemistry.

[61]  T. Niidome,et al.  Preparation of primary amine-modified gold nanoparticles and their transfection ability into cultivated cells. , 2004, Chemical communications.

[62]  F. Szoka,et al.  Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. , 1993, Bioconjugate chemistry.

[63]  E. Giralt,et al.  Highly efficient, nonpeptidic oligoguanidinium vectors that selectively internalize into mitochondria. , 2005, Journal of the American Chemical Society.

[64]  Eiichi Nakamura,et al.  Functionalized Fullerene as an Artificial Vector for Transfection. , 2000, Angewandte Chemie.

[65]  C. Akey Visualization of transport-related configurations of the nuclear pore transporter. , 1990, Biophysical journal.

[66]  T. Reineke,et al.  Poly(glycoamidoamine)s for gene delivery. structural effects on cellular internalization, buffering capacity, and gene expression. , 2007, Bioconjugate chemistry.

[67]  Kemin Wang,et al.  Bioconjugated nanoparticles for DNA protection from cleavage. , 2003, Journal of the American Chemical Society.

[68]  G. Lukács,et al.  Intracellular barriers to non-viral gene transfer. , 2002, Current gene therapy.

[69]  M Monsigny,et al.  Putative role of chloroquine in gene transfer into a human hepatoma cell line by DNA/lactosylated polylysine complexes. , 1996, Experimental cell research.

[70]  Y. Aoyama,et al.  Saccharide-Directed Cell Recognition and Molecular Delivery Using Macrocyclic Saccharide Clusters: Masking of Hydrophobicity to Enhance the Saccharide Specificity , 2000 .

[71]  T. Reineke,et al.  New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells. , 2004, Journal of the American Chemical Society.

[72]  D. Balding,et al.  HLA Sequence Polymorphism and the Origin of Humans , 2006 .

[73]  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.

[74]  K. Gupta,et al.  Polyethylenimine nanoparticles as efficient transfecting agents for mammalian cells. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[75]  C. Rivetti,et al.  DNA condensation and cell transfection properties of guanidinium calixarenes: dependence on macrocycle lipophilicity, size, and conformation. , 2006, Journal of the American Chemical Society.

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

[77]  R. Lockey,et al.  Cationic silica nanoparticles as gene carriers: synthesis, characterization and transfection efficiency in vitro and in vivo. , 2004, Journal of nanoscience and nanotechnology.

[78]  L. Lerman A transition to a compact form of DNA in polymer solutions. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[79]  N. M. Rao,et al.  Synthesis and in vitro evaluation of glutamide-containing cationic lipids for gene delivery. , 2006, Bioconjugate chemistry.

[80]  T. Dull,et al.  Third-generation, self-inactivating gp91(phox) lentivector corrects the oxidase defect in NOD/SCID mouse-repopulating peripheral blood-mobilized CD34+ cells from patients with X-linked chronic granulomatous disease. , 2002, Blood.

[81]  Jiyoung M Dang,et al.  Natural polymers for gene delivery and tissue engineering. , 2006, Advanced drug delivery reviews.

[82]  Vincent M Rotello,et al.  Gold nanoparticle-mediated transfection of mammalian cells. , 2002, Bioconjugate chemistry.

[83]  J. Kimmelman Recent developments in gene transfer: risk and ethics , 2005, BMJ : British Medical Journal.

[84]  Daniel G. Anderson,et al.  Semi-automated synthesis and screening of a large library of degradable cationic polymers for gene delivery. , 2003, Angewandte Chemie.

[85]  T. Chiles,et al.  Highly efficient molecular delivery into mammalian cells using carbon nanotube spearing , 2005, Nature Methods.

[86]  K. Leong,et al.  Multifunctional nanorods for gene delivery , 2003, Nature materials.

[87]  Yi-Cheng Chen,et al.  DNA-gold nanorod conjugates for remote control of localized gene expression by near infrared irradiation. , 2006, Journal of the American Chemical Society.

[88]  C. Plank,et al.  Magnetofection Potentiates Gene Delivery to Cultured Endothelial Cells , 2003, Journal of Vascular Research.

[89]  T. Reineke,et al.  Hydroxyl stereochemistry and amine number within poly(glycoamidoamine)s affect intracellular DNA delivery. , 2005, Journal of the American Chemical Society.

[90]  T. Niidome,et al.  Artificial viruses and their application to gene delivery. Size-controlled gene coating with glycocluster nanoparticles. , 2003, Journal of the American Chemical Society.

[91]  Q. Shi,et al.  Characterization of folate-chitosan-DNA nanoparticles for gene therapy. , 2006, Biomaterials.

[92]  H. Okayama,et al.  Gene delivery by aminofullerenes: structural requirements for efficient transfection. , 2006, Chemistry, an Asian journal.

[93]  D. Fischer,et al.  Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives , 2005, The journal of gene medicine.

[94]  C. Feldherr,et al.  Translocation of RNA-coated gold particles through the nuclear pores of oocytes , 1988, The Journal of cell biology.

[95]  M. Aoki,et al.  HVJ-envelope vector for gene transfer into central nervous system. , 2003, Biochemical and biophysical research communications.

[96]  T. Blankenstein,et al.  Vectors in cancer therapy: how will they deliver? , 1995, Cancer gene therapy.

[97]  Jun Li,et al.  Cationic Supramolecules Composed of Multiple Oligoethylenimine‐Grafted β‐Cyclodextrins Threaded on a Polymer Chain for Efficient Gene Delivery , 2006 .

[98]  Vincent M Rotello,et al.  Light-regulated release of DNA and its delivery to nuclei by means of photolabile gold nanoparticles. , 2006, Angewandte Chemie.

[99]  R. Peters Nucleo‐cytoplasmic flux and intracellular mobility in single hepatocytes measured by fluorescence microphotolysis. , 1984, The EMBO journal.

[100]  S. Zahler,et al.  Magnetofection--a highly efficient tool for antisense oligonucleotide delivery in vitro and in vivo. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[101]  M. Prato,et al.  Carbon nanotubes as nanomedicines: from toxicology to pharmacology. , 2006, Advanced drug delivery reviews.

[102]  Zhixin Guo,et al.  Carbon Nanotube Delivery of the GFP Gene into Mammalian Cells , 2006, Chembiochem : a European journal of chemical biology.

[103]  You Han Bae,et al.  pH-responsive sulfonamide/PEI system for tumor specific gene delivery: an in vitro study. , 2006, Biomacromolecules.

[104]  J. Wolff,et al.  A nuclear localization signal can enhance both the nuclear transport and expression of 1 kb DNA. , 1999, Journal of cell science.

[105]  H. O'brodovich,et al.  Metabolic instability of plasmid DNA in the cytosol: a potential barrier to gene transfer , 1999, Gene Therapy.

[106]  Gary R Whittaker Virus nuclear import. , 2003, Advanced drug delivery reviews.

[107]  T. Schiestel,et al.  A nonviral DNA delivery system based on surface modified silica-nanoparticles can efficiently transfect cells in vitro. , 2000, Bioconjugate chemistry.

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

[109]  E. Wagner,et al.  Different strategies for formation of pegylated EGF-conjugated PEI/DNA complexes for targeted gene delivery. , 2001, Bioconjugate chemistry.

[110]  C. K. Chan,et al.  Enhancement of polylysine-mediated transferrinfection by nuclear localization sequences: polylysine does not function as a nuclear localization sequence. , 1999, Human gene therapy.

[111]  Robert Langer,et al.  Parallel synthesis and biophysical characterization of a degradable polymer library for gene delivery. , 2003, Journal of the American Chemical Society.

[112]  M. Ogris,et al.  PEGylated DNA/transferrin–PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery , 1999, Gene Therapy.

[113]  M. Sullivan,et al.  Development of a novel gene delivery scaffold utilizing colloidal gold–polyethylenimine conjugates for DNA condensation , 2003, Gene Therapy.

[114]  C Alexiou,et al.  Clinical applications of magnetic drug targeting. , 2001, The Journal of surgical research.

[115]  F. Liu,et al.  Polyethylene glycol-grafted poly-L-lysine as polymeric gene carrier. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[116]  H. Hofmann,et al.  Enhancement of the efficiency of non-viral gene delivery by application of pulsed magnetic field , 2006, Nucleic acids research.

[117]  Nucleocytoplasmic Transport , 1996, Science.

[118]  N. M. Rao,et al.  Cell Biological and Biophysical Aspects of Lipid-mediated Gene Delivery , 2006, Bioscience reports.

[119]  Daniele Gerion,et al.  Fluorescent CdSe/ZnS nanocrystal-peptide conjugates for long-term, nontoxic imaging and , 2004 .

[120]  W. Xiong,et al.  Poly(l‐lysine)‐modified silica nanoparticles for the delivery of antisense oligonucleotides , 2004, Biotechnology and applied biochemistry.

[121]  C. Joe,et al.  Folate receptor mediated intracellular protein delivery using PLL-PEG-FOL conjugate. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[122]  N. Pante,et al.  Nuclear pore complex is able to transport macromolecules with diameters of about 39 nm. , 2002, Molecular biology of the cell.

[123]  C. Pouton,et al.  Nuclear import of polypeptides, polynucleotides and supramolecular complexes. , 1998, Advanced drug delivery reviews.

[124]  M. Kurisawa,et al.  Synthesis and characterization of chitosan-g-poly(ethylene glycol)-folate as a non-viral carrier for tumor-targeted gene delivery. , 2007, Biomaterials.

[125]  J. Nah,et al.  DNA delivery using low molecular water‐soluble chitosan nanocomplex as a biomedical device , 2006 .

[126]  L G Griffith,et al.  Quantitative comparison of polyethylenimine formulations and adenoviral vectors in terms of intracellular gene delivery processes , 2005, Gene Therapy.

[127]  R Weissleder,et al.  Superparamagnetic iron oxide: pharmacokinetics and toxicity. , 1989, AJR. American journal of roentgenology.

[128]  A. Fischer,et al.  Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. , 2002, The New England journal of medicine.

[129]  Shubiao Zhang,et al.  Toxicity of cationic lipids and cationic polymers in gene delivery. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[130]  Robert Langer,et al.  A polymer library approach to suicide gene therapy for cancer. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[131]  M. Wolfert,et al.  Chloroquine and amphipathic peptide helices show synergistic transfection in vitro , 1998, Gene Therapy.

[132]  M. Buchberger,et al.  Coupling of cell-binding ligands to polyethylenimine for targeted gene delivery , 1997, Gene Therapy.

[133]  T. Senden,et al.  Supramolecular structure and nuclear targeting efficiency determine the enhancement of transfection by modified polylysines , 2000, Gene Therapy.

[134]  R. Lanford,et al.  The effects of variations in the number and sequence of targeting signals on nuclear uptake , 1988, The Journal of cell biology.

[135]  Se-kwon Kim,et al.  Characterization of (aminoethyl)chitin/DNA nanoparticle for gene delivery. , 2006, Biomacromolecules.