Polymeric microspheres as stabilizing anchors for oligonucleotide delivery to dendritic cells.

The aim of this study is to evaluate a novel microspheric vector for delivery of oligonucleotides (ODN) into dendritic cells (DC). A requirement of decoy-based modulation of transcriptional activities in DC is that the ODN would have to accumulate inside the cell. Using an ex vivo DC culture model, we demonstrate that anionic microspheres (MS) coated with an ornithine/histadine-based cationic peptide (O10H6) is an effective carrier of short ODN. This method does not disrupt the colloidal nature of the microspheric particles. The MS provide stabilizing effect on DNA and O10H6 complexation. Accumulation of ODN in DC is greatly enhanced with the surface modified MS. Taken together, these data demonstrate that the self assembly system of MS(O10H6) is an effective delivery vehicle for DNA-based modulation of DC functions.

[1]  P. Couvreur,et al.  Polyalkylcyanoacrylate Nanoparticles as Polymeric Carriers for Antisense Oligonucleotides , 1992, Pharmaceutical Research.

[2]  E. McClelland,et al.  A cationic peptide consists of ornithine and histidine repeats augments gene transfer in dendritic cells. , 2003, Molecular immunology.

[3]  D. Baltimore,et al.  Regulation of the NF-kappa B/rel transcription factor and I kappa B inhibitor system. , 1993, Current opinion in cell biology.

[4]  J. Ulmer,et al.  Microparticles for the delivery of DNA vaccines , 2004, Immunological reviews.

[5]  Ranjeny Thomas,et al.  Sustained Activation of NF-Antigen-Presenting Function Through CD 40 Ligation Conditions Dendritic Cell , 2002 .

[6]  H. Merkle,et al.  Competitive adsorption of serum proteins at microparticles affects phagocytosis by dendritic cells. , 2003, Biomaterials.

[7]  R. Steinman,et al.  The dendritic cell system and its role in immunogenicity. , 1991, Annual review of immunology.

[8]  A. Ichinose,et al.  Binding of Cationic α-Helical Peptides to Plasmid DNA and Their Gene Transfer Abilities into Cells* , 1997, The Journal of Biological Chemistry.

[9]  P. Midoux,et al.  Histidylated polylysine as DNA vector: elevation of the imidazole protonation and reduced cellular uptake without change in the polyfection efficiency of serum stabilized negative polyplexes. , 2001, Bioconjugate chemistry.

[10]  Hongmei Shen,et al.  Gene delivery to dendritic cells facilitated by a tumor necrosis factor alpha-competing peptide. , 2004, Molecular immunology.

[11]  R. Gambari,et al.  Complexation to Cationic Microspheres of Double-Stranded Peptide Nucleic Acid-DNA Chimeras Exhibiting Decoy Activity , 2004, Journal of Biomedical Science.

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

[13]  David Baltimore,et al.  Regulation of the NF-?B/rel transcription factor and I?B inhibitor system , 1993 .

[14]  D. McDonald,et al.  Plasmid DNA adsorbed onto cationic microparticles mediates target gene expression and antigen presentation by dendritic cells , 2000, Gene Therapy.

[15]  M. Gumbleton,et al.  Polylysine and Polyornithine Gene Transfer Complexes: A Study of Complex Stability and Cellular Uptake as a Basis for their Differential in-vitro Transfection Efficiency , 2002, Journal of drug targeting.

[16]  M. Feldmann,et al.  Antigen‐Specific T‐Cell Downregulation by Human Dendritic Cells Following Blockade of NF‐κB , 2003, Scandinavian journal of immunology.

[17]  C. Pichon,et al.  Intracellular processing and stability of DNA complexed with histidylated polylysine conjugates , 2002, The journal of gene medicine.

[18]  W. Mark Saltzman,et al.  Enhancement of transfection by physical concentration of DNA at the cell surface , 2000, Nature Biotechnology.

[19]  K. Rice,et al.  Peptide-mediated gene delivery: influence of peptide structure on gene expression. , 1997, Bioconjugate chemistry.

[20]  H. Mollenkopf,et al.  Enhanced protective efficacy of a tuberculosis DNA vaccine by adsorption onto cationic PLG microparticles. , 2004, Vaccine.

[21]  C. Pouton,et al.  Polycation-DNA complexes for gene delivery: a comparison of the biopharmaceutical properties of cationic polypeptides and cationic lipids. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[22]  P. Robbins,et al.  Marked Prolongation of Cardiac Allograft Survival by Dendritic Cells Genetically Engineered with NF-κB Oligodeoxyribonucleotide Decoys and Adenoviral Vectors Encoding CTLA4-Ig1 , 2002, The Journal of Immunology.

[23]  K. Rice,et al.  Comparative gene transfer efficiency of low molecular weight polylysine DNA-condensing peptides. , 1999, The journal of peptide research : official journal of the American Peptide Society.

[24]  D. Tyler,et al.  Dendritic cell gene therapy. , 2002, Surgical oncology clinics of North America.

[25]  D. Klatzmann,et al.  Heterogeneity of mouse spleen dendritic cells: in vivo phagocytic activity, expression of macrophage markers, and subpopulation turnover. , 1998, Journal of immunology.

[26]  M. Monsigny,et al.  Membrane permeabilization and efficient gene transfer by a peptide containing several histidines. , 1998, Bioconjugate chemistry.

[27]  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.

[28]  P. Couvreur,et al.  Adsorption of Oligonucleotides onto Polyisohexylcyanoacrylate Nanoparticles Protects Them Against Nucleases and Increases Their Cellular Uptake , 1994, Pharmaceutical Research.

[29]  Hans P. Merkle,et al.  Phagocytosis and Phagosomal Fate of Surface-Modified Microparticles in Dendritic Cells and Macrophages , 2003, Pharmaceutical Research.

[30]  Manmohan J. Singh,et al.  Cationic microparticles: A potent delivery system for DNA vaccines. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Hadgraft,et al.  Examination of the biophysical interaction between plasmid DNA and the polycations, polylysine and polyornithine, as a basis for their differential gene transfection in-vitro. , 2000, International journal of pharmaceutics.

[32]  C. Pichot,et al.  Adsorption of Single-Stranded DNA Fragments onto Cationic Aminated Latex Particles , 1997 .

[33]  D. Luo,et al.  A self-assembled, modular DNA delivery system mediated by silica nanoparticles. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Manmohan J. Singh,et al.  Charged polylactide co-glycolide microparticles as antigen delivery systems , 2004, Expert opinion on biological therapy.

[35]  Manmohan J. Singh,et al.  Microparticles as vaccine adjuvants and delivery systems , 2003, Expert review of vaccines.

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

[37]  C. Hélène,et al.  Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated Ha-ras-mediated cell proliferation and tumorigenicity in nude mice. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Feldmann,et al.  Antigen Presentation by Murine Dendritic Cells is Nuclear Factor‐kappa B Dependent Both In Vitro and In Vivo , 2003, Scandinavian journal of immunology.

[39]  C. Pouton,et al.  Pharmaceutical and biological properties of poly(amino acid)/DNA polyplexes. , 1999, Journal of drug targeting.

[40]  Manmohan J. Singh,et al.  The Effect of CTAB Concentration in Cationic PLG Microparticles on DNA Adsorption and in Vivo Performance , 2003, Pharmaceutical Research.

[41]  M. Cotten,et al.  Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[42]  C. Hélène,et al.  Antisense effects of cholesterol-oligodeoxynucleotide conjugates associated with poly(alkylcyanoacrylate) nanoparticles. , 1995, European Journal of Biochemistry.

[43]  A. Zimmer,et al.  Comparison of antisense oligonucleotide drug delivery systems. , 2004, Journal of controlled release : official journal of the Controlled Release Society.