Publikationsserver der Universitätsbibliothek Marburg

Titel:Composite nanocarriers for nucleic acid delivery
Autor:Pinnapireddy, Shashank Reddy
Weitere Beteiligte: Bakowsky, Udo (Prof. Dr)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0252
URN: urn:nbn:de:hebis:04-z2017-02529
DOI: https://doi.org/10.17192/z2017.0252
DDC: Naturwissenschaften
Titel(trans.):Komposit nicht-viraler Gentransfersysteme zum Transfer von Nukleinsäuren
Publikationsdatum:2017-06-01
Lizenz:https://creativecommons.org/licenses/by-nc-nd/4.0/

Dokument

Schlagwörter:
Entzündung, gene delivery, Gene Therapy, RNA interference, Gentransfer, Ultraschall, Liposomes, Inflammation, Gentechnologie, RNS-Interferenz, ultrasound, Liposom

Summary:
Supported with a strong literature background, this thesis elaborately describes the perspectives of an efficient, biocompatible delivery system capable of transfecting both in vitro and in vivo with minimal toxicity. A detailed study of the lipopolyplexes was performed to evaluate its efficacy and capabilities yielding consistent results.The thesis deals with aspects such as gene delivery, RNA interference and vectors used for the delivery. Non-viral vectors, especially polymer and liposomal based gene delivery vehicles are reviewed. These formed the basis for the composite nanocarrier system, lipopolyplex used in this study. Advantages and disadvantages of liposomal and polymer based gene delivery systems are reviewed. Composition, structural characteristics and physicochemical properties of lipopolyplexes are discussed. Physical methods for enhancing the gene transfer using lipopolyplexes via photochemical internalisation and ultrasound enhanced gene transfer are described. A therapeutic anti-inflammatory model to evaluate the efficacy of the lipopolyplexes has been described. The necessity of toxicity and haemocompatibility studies for the evaluation of delivery vehicles have been summarised. Chorioallantoic membrane model has been described with the aim to prove the biocompatibility and efficacy of the lipopolyplexes in vivo.

Zusammenfassung:
Die vorliegende Arbeit beschreibt ausführlich die Perspektiven eines effizienten und biokompatiblen Gentransfersystems, welches sowohl in vitro als auch in vivo verwendbar ist. Zur Überprüfung der Wirksamkeit und Einsatzfähigkeit der Lipopolyplexe wurden im Vorfeld eingehende physikalisch chemische Charakterisierungen durchgeführt. Einen ausführlichen Überblick über die potentiellen Möglichkeiten des Gentransfers, die RNA-Interferenz und sogenannte Nicht-virale Vektoren werden in der Einleitung gegeben. Einleitend sind zunächst die nicht-virale Vektoren, insbesondere die Polymer- und Liposomale Transfersysteme dargestellt. Diese Transfersysteme bilden die Grundlage für das zusammengesetzte, in dieser Arbeit vorgestellte, Nanoträgersystem „Lipopolyplex“. Anschließend erfolgt eine Diskussion über ihre strukturellen Eigenschaften. Moderne physikalische Methoden (Ultraschall bzw. Photodynamik), welche zur Verbesserung des Gentransfers mit Lipopolyplexen dienen können, werden ebenfalls dargestellt. Bei diesen Methoden handelt es sich insbesondere um die photochemische Internalisierung (PCI, Photodynamik) und der durch Ultraschall verstärkte Gentransfer (UEGT). Darüber hinaus wird ein therapeutisches antiinflammatorisches Modell zur Bewertung der Wirksamkeit von Lipopolyplexen als erster therapeutischer Ansatz dargestellt. Zusätzlich werden die Notwendigkeit der Toxizitäts- und Hämokompatibilitätsstudien für die Evaluierung von Gentransfersysteme beschrieben und zusammengefasst. Ein weiteres Modell, das sogenannte Chorioallantoismembran Modell (CAM) diente der in vivo Charakterisierung, der Biokompatibilität und der Effizienz der Lipopolyplexen.

Bibliographie / References

  1. [93] T. Ohtsuki, S. Miki, S. Kobayashi, T. Haraguchi, E. Nakata, K. Hirakawa, K. Sumita, K. Watanabe, S. Okazaki, The molecular mechanism of photochemical internalization of cell penetrating peptide-cargo-photosensitizer conjugates, Scientific Reports, Published online: 21 December 2015; | doi:10.1038/srep18577, (2015).
  2. [139] A. Ozcetin, A. Aigner, U. Bakowsky, A chorioallantoic membrane model for the determination of anti-angiogenic effects of imatinib, Eur J Pharm Biopharm, 85 (2013) 711- 715.
  3. [175] M.S. Shim, Y.J. Kwon, Acid-Responsive Linear Polyethylenimine for Efficient, Specific, and Biocompatible siRNA Delivery, Bioconjugate Chemistry, (2009).
  4. [155] J.W. Wiseman, C.A. Goddard, D. McLelland, W.H. Colledge, A comparison of linear and branched polyethylenimine (PEI) with DCChol/DOPE liposomes for gene delivery to epithelial cells in vitro and in vivo, Gene Therapy, 10 (2003) 1654-1662.
  5. [41] S.S. Bansal, M. Goel, F. Aqil, M.V. Vadhanam, R.C. Gupta, Advanced Drug Delivery Systems of Curcumin for Cancer Chemoprevention, (2011).
  6. [120] D.S. Zhuk, P.A. Gembitskii, V.A. Kargin, Advances in the chemistry of Polyethyleneimine (Polyaziridine), Russian Chemical Reviews, 34 (1965) 515-527.
  7. [61] S. Werth, B. Urban-Klein, L. Dai, S. Hobel, M. Grzelinski, U. Bakowsky, F. Czubayko, A. Aigner, A low molecular weight fraction of polyethylenimine (PEI) displays increased transfection efficiency of DNA and siRNA in fresh or lyophilized complexes, J Control Release, 112 (2006) 257-270.
  8. [69] T. Endres, M. Zheng, A. Kılıç, A. Turowska, M. Beck-Broichsitter, H. Renz, O.M. Merkel, T. Kissel, Amphiphilic Biodegradable PEG-PCL-PEI Triblock Copolymers for FRET-Capable in Vitro and in Vivo Delivery of siRNA and Quantum Dots, (2014).
  9. [107] J. Sundaram, B.R. Mellein, S. Mitragotri, An Experimental and Theoretical Analysis of Ultrasound-Induced Permeabilization of Cell Membranes, in: Biophys J, 2003, pp. 3087-3101.
  10. [49] S.D. Patil, D.G. Rhodes, D.J. Burgess, Anionic liposomal delivery system for DNA transfection, in: AAPS J, 2004, pp. 13-22.
  11. [48] S. Khiati, N. Pierre, S. Andriamanarivo, M.W. Grinstaff, N. Arazam, F. Nallet, L. Navailles, P. Barthelemy, Anionic nucleotide--lipids for in vitro DNA transfection, Bioconjug Chem, 20 (2009) 1765-1772.
  12. [67] D. Fischer, T. Bieber, Y. Li, H.P. Elsasser, T. Kissel, A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity, Pharm Res, 16 (1999) 1273-1279.
  13. [12] S.M. Hammond, E. Bernstein, D. Beach, G.J. Hannon, An RNA-directed nuclease mediates post-transcriptional gene silencingin Drosophila cells, Nature, 404 (2000) 293-296.
  14. [151] J. Schaefer, C. Schulze, E.E. Marxer, U.F. Schaefer, W. Wohlleben, U. Bakowsky, C.M. Lehr, Atomic force microscopy and analytical ultracentrifugation for probing nanomaterial protein interactions, ACS Nano, 6 (2012) 4603-4614.
  15. [78] S.M. Moghimi, P. Symonds, J.C. Murray, A.C. Hunter, G. Debska, A. Szewczyk, A twostage poly(ethylenimine)-mediated cytotoxicity: implications for gene transfer/therapy, Mol Ther, 11 (2005) 990-995.
  16. [56] O. Boussif, F. Lezoualc'h, M.A. Zanta, M.D. Mergny, D. Scherman, B. Demeneix, J.P. Behr, A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine, Proc Natl Acad Sci U S A, 92 (1995) 7297-7301.
  17. [4] G.D. Ferrari S, Alton EW., Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis, 54 (2002) 1373-1393.
  18. [40] F. Aqil, R. Munagala, J. Jeyabalan, M.V. Vadhanam, Bioavailability of phytochemicals and its enhancement by drug delivery systems, Cancer Lett, 334 (2013) 133-141.
  19. [124] Biological evaluation of medical devices Part 5: Tests for in vitro cytotoxicity, in: IS0 10 993-5, EN 30 993-5, 199, 2009.
  20. [150] H. Lodish, A. Berk, S.L. Zipursky, P. Matsudaira, D. Baltimore, J. Darnell, Biomembranes: Structural Organization and Basic Functions, in: Molecular Cell Biology, W. H. Freeman, 2000.
  21. [149] V. Pector, J. Backmann, D. Maes, M. Vandenbranden, J.M. Ruysschaert, Biophysical and structural properties of DNA.diC(14)-amidine complexes. Influence of the DNA/lipid ratio, J Biol Chem, 275 (2000) 29533-29538.
  22. [76] C. Peetla, A. Stine, V. Labhasetwar, Biophysical interactions with model lipid membranes: applications in drug discovery and drug delivery, Mol Pharm, 6 (2009) 1264-1276.
  23. [80] M. Breunig, U. Lungwitz, R. Liebl, A. Goepferich, Breaking up the correlation between efficacy and toxicity for nonviral gene delivery, Proc Natl Acad Sci U S A, 104 (2007) 14454- 14459.
  24. [114] G.L. Nicolson, Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites, Biochim Biophys Acta, 948 (1988) 175-224.
  25. [45] J. Marshall, N.S. Yew, S.J. Eastman, C. Jiang, R.K. Scheule, S.H. Cheng, Cationic LipidMediated Gene Delivery to the Airways, 1 ed., Elsevier, 1999.
  26. [43] L. Wasungu, D. Hoekstra, Cationic lipids, lipoplexes and intracellular delivery of genes, J Control Release, 116 (2006) 255-264.
  27. [83] J. Zabner, A.J. Fasbender, T. Moninger, K.A. Poellinger, M.J. Welsh, Cellular and molecular barriers to gene transfer by a cationic lipid, J Biol Chem, 270 (1995) 18997-19007.
  28. [142] A. von Harpe, H. Petersen, Y. Li, T. Kissel, Characterization of commercially available and synthesized polyethylenimines for gene delivery, J Control Release, 69 (2000) 309-322.
  29. [54] U.K. Laemmli, Characterization of DNA condensates induced by poly(ethylene oxide) and polylysine, Proc Natl Acad Sci U S A, 72 (1975) 4288-4292.
  30. [73] G. Borchard, Chitosans for gene delivery, Adv Drug Deliv Rev, 52 (2001) 145-150.
  31. [28] F. Szoka, Jr., D. Papahadjopoulos, Comparative properties and methods of preparation of lipid vesicles (liposomes), Annu Rev Biophys Bioeng, 9 (1980) 467-508.
  32. [171] U. Bakowsky, G. Schumacher, C. Gege, R.R. Schmidt, U. Rothe, G. Bendas, Cooperation between lateral ligand mobility and accessibility for receptor recognition in selectin-induced cell rolling, Biochemistry, 41 (2002) 4704-4712.
  33. [104] J. Brussler, E. Marxer, A. Becker, R. Schubert, J. Schummelfeder, C. Nimsky, U. Bakowsky, Correlation of structure and echogenicity of nanoscaled ultrasound contrast agents in vitro, Colloids Surf B Biointerfaces, 117 (2014) 206-215.
  34. [170] T. Narita, N. Kawakami-Kimura, N. Matsuura, J. Hosono, R. Kannagi, Corticosteroids and medroxyprogesterone acetate inhibit the induction of E-selectin on the vascular endothelium by MDA-MB-231 breast cancer cells, Anticancer Res, 15 (1995) 2523-2527.
  35. [55] T.G. Park, J.H. Jeong, S.W. Kim, Current status of polymeric gene delivery systems, Adv Drug Deliv Rev, 58 (2006) 467-486.
  36. [174] V. Kafil, Y. Omidi, Cytotoxic Impacts of Linear and Branched Polyethylenimine Nanostructures in A431 Cells, Bioimpacts, 1 (2011) 23-30.
  37. [65] A. Aigner, D. Fischer, T. Merdan, C. Brus, T. Kissel, F. Czubayko, Delivery of unmodified bioactive ribozymes by an RNA-stabilizing polyethylenimine (LMW-PEI) efficiently downregulates gene expression, Gene Ther, 9 (2002) 1700-1707.
  38. [16] A. Aigner, Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo, J Biomed Biotechnol, 2006 (2006).
  39. [13] M. Tijsterman, R.H. Plasterk, Dicers at RISC; the mechanism of RNAi, Cell, 117 (2004) 1-3.
  40. [35] G. Scherphof, F. Roerdink, M. Waite, J. Parks, Disintegration of phosphatidylcholine liposomes in plasma as a result of interaction with high-density lipoproteins, Biochim Biophys Acta, 542 (1978) 296-307.
  41. [66] C. Brus, H. Petersen, A. Aigner, F. Czubayko, T. Kissel, Efficiency of polyethylenimines and polyethylenimine-graft-poly (ethylene glycol) block copolymers to protect oligonucleotides against enzymatic degradation, Eur J Pharm Biopharm, 57 (2004) 427-430.
  42. [159] N.P. Gabrielson, D.W. Pack, Efficient polyethylenimine-mediated gene delivery proceeds via a caveolar pathway in HeLa cells, J Control Release, 136 (2009) 54-61.
  43. [132] R.L. Steere, Electron microscopy of structural detail in frozen biological specimens, J Biophys Biochem Cytol, 3 (1957) 45-60.
  44. [161] N. Oh, J.H. Park, Endocytosis and exocytosis of nanoparticles in mammalian cells, Int J Nanomedicine, 9 (2014) 51-63.
  45. [145] I. Mellman, Endocytosis and molecular sorting, Annu Rev Cell Dev Biol, 12 (1996) 575- 625.
  46. [98] A. Ndoye, J.L. Merlin, A. Leroux, G. Dolivet, P. Erbacher, J.P. Behr, K. Berg, F. Guillemin, Enhanced gene transfer and cell death following p53 gene transfer using photochemical internalisation of glucosylated PEI-DNA complexes, J Gene Med, 6 (2004) 884- 894.
  47. [172] B. Carneiro, A.C. Braga, M.N. Batista, M. Harris, P. Rahal, Evaluation of canonical siRNA and Dicer substrate RNA for inhibition of hepatitis C virus genome replication--a comparative study, PLoS One, 10 (2015) e0117742.
  48. [59] A. Akinc, M. Thomas, A.M. Klibanov, R. Langer, Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis, J Gene Med, 7 (2005) 657-663.
  49. [19] C. Janich, S.R. Pinnapireddy, F. Erdmann, T. Groth, A. Langner, U. Bakowsky, C. Wolk, Fast therapeutic DNA internalization - A high potential transfection system based on a peptide mimicking cationic lipid, Eur J Pharm Biopharm, (2016).
  50. [77] M. Thomas, J.J. Lu, Q. Ge, C. Zhang, J. Chen, A.M. Klibanov, Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung, Proc Natl Acad Sci U S A, 102 (2005) 5679-5684.
  51. [117] I. Wrobel, D. Collins, Fusion of cationic liposomes with mammalian cells occurs after endocytosis, Biochim Biophys Acta, 1235 (1995) 296-304.
  52. [44] I.S. Zuhorn, J.B.F.N. Engberts, D. Hoekstra, Gene delivery by cationic lipid vectors: overcoming cellular barriers, European Biophysics Journal, 36 (2007) 349-362.
  53. [52] M.C. Garnett, Gene-delivery systems using cationic polymers, Crit Rev Ther Drug Carrier Syst, 16 (1999) 147-207.
  54. [7] I.M. Verma, Gene therapy: hopes, hypes, and hurdles, Mol Med, 1 (1994) 2-3.
  55. [2] E. Bender, Gene therapy: Industrial strength, Nature, 537 (2016).
  56. [8] I.M. Verma, N. Somia, Gene therapy -- promises, problems and prospects, Nature, 389 (1997) 239-242.
  57. [111] S.W. Tas, M.J. Vervoordeldonk, P.P. Tak, Gene Therapy Targeting Nuclear Factor-κB: Towards Clinical Application in Inflammatory Diseases and Cancer, Curr Gene Ther, 9 (2009) 160-170.
  58. [9] N. Somia, I.M. Verma, Gene therapy: trials and tribulations, Nature Reviews Genetics, 1 (2000) 91-99.
  59. [110] S. Wirtz, M.F. Neurath, Gene transfer approaches for the treatment of inflammatory bowel disease, Gene Therapy, 10 (2003) 854-860.
  60. [163] M. Tomizawa, F. Shinozaki, Y. Motoyoshi, T. Sugiyama, S. Yamamoto, M. Sueishi, Sonoporation: Gene transfer using ultrasound, World J Methodol, 3 (2013) 39-44.
  61. [105] S. Mitragotri, Healing sound: the use of ultrasound in drug delivery and other therapeutic applications, Nature Reviews Drug Discovery, 4 (2005) 255-260.
  62. [135] M.P. Bevilacqua, J.S. Pober, D.L. Mendrick, R.S. Cotran, M.A. Gimbrone, Identification of an inducible endothelial-leukocyte adhesion molecule, Proc Natl Acad Sci U S A, 84 (1987) 9238-9242.
  63. [119] K. Crook, B.J. Stevenson, M. Dubouchet, D.J. Porteous, Inclusion of cholesterol in DOTAP transfection complexes increases the delivery of DNA to cells in vitro in the presence of serum, Gene Ther, 5 (1998) 137-143.
  64. [169] N. Matsuura, T. Narita, C. Mitsuoka, N. Kimura, R. Kannagi, T. Imai, H. Funahashi, H. Takagi, Increased concentration of soluble E-selectin in the sera of breast cancer patients, Anticancer Res, 17 (1997) 1367-1372.
  65. [34] K. Hoekstra, J. van Renswoude, R. Tomasini, G. Scherphof, Interaction of phospholipid vesicles with rat hepatocytes: further characterization of vesicle-cell surface interaction; use of serum as a physiological modulator, Membr Biochem, 4 (1981) 129-147.
  66. [33] P.R. Cullis, A. Chonn, S.C. Semple, Interactions of liposomes and lipid-based carrier systems with blood proteins: Relation to clearance behaviour in vivo, Adv Drug Deliv Rev, 32 (1998) 3-17.
  67. [87] P.J. Lou, H.R. Jager, L. Jones, T. Theodossy, S.G. Bown, C. Hopper, Interstitial photodynamic therapy as salvage treatment for recurrent head and neck cancer, Br J Cancer, 91 (2004) 441-446.
  68. [99] I. Donald, J. Macvicar, T.G. Brown, Investigation Of Abdominal Masses By Pulsed Ultrasound, The Lancet, 271 (1958) 1188-1195.
  69. [148] D. Fischer, Y. Li, B. Ahlemeyer, J. Krieglstein, T. Kissel, In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis, Biomaterials, 24 (2003) 1121-1131.
  70. [166] D. Omata, Y. Negishi, S. Yamamura, S. Hagiwara, Y. Endo-Takahashi, R. Suzuki, K. Maruyama, M. Nomizu, Y. Aramaki, Involvement of Ca(2)(+) and ATP in enhanced gene delivery by bubble liposomes and ultrasound exposure, Mol Pharm, 9 (2012) 1017-1023.
  71. [88] C. Pais-Silva, D. de Melo-Diogo, I.J. Correia, IR780-loaded TPGS-TOS micelles for breast cancer photodynamic therapy, European Journal of Pharmaceutics and Biopharmaceutics, 113 (2017) 108-117.
  72. [115] K. K.J., V. T.K., Isotherms of Dipalmitoylphosphatidylcholine (DPPC) Monolayers: Features Revealed and Features Obscured - ScienceDirect, Journal of Colloid and Interface Science, (1996).
  73. [37] P.L. Felgner, T.R. Gadek, M. Holm, R. Roman, H.W. Chan, M. Wenz, J.P. Northrop, G.M. Ringold, M. Danielsen, Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure, Proc Natl Acad Sci U S A, 84 (1987) 7413-7417.
  74. [42] V. Oberle, U. Bakowsky, I.S. Zuhorn, D. Hoekstra, Lipoplex formation under equilibrium conditions reveals a three-step mechanism, Biophys J, 79 (2000) 1447-1454.
  75. [18] A. Ewe, O. Panchal, S.R. Pinnapireddy, U. Bakowsky, S. Przybylski, A. Temme, A. Aigner, Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo, Nanomedicine, (2016).
  76. [75] J. Schäfer, S. Hobel, U. Bakowsky, A. Aigner, Liposome-polyethylenimine complexes for enhanced DNA and siRNA delivery, Biomaterials, 31 (2010) 6892-6900.
  77. [27] D.D. Lasic, Liposomes : from physics to applications, Elsevier, Amsterdam; New York, 1993.
  78. [164] E.C. Unger, E. Hersh, M. Vannan, T.O. Matsunaga, T. McCreery, Local drug and gene delivery through microbubbles, Prog Cardiovasc Dis, 44 (2001) 45-54.
  79. [72] O. Samsonova, C. Pfeiffer, M. Hellmund, O.M. Merkel, T. Kissel, Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?, Polymers, 3 (2011) 693-718.
  80. [38] J.T. Dingle, P.J. Jacques, I.H. Shaw, Lysosomes in applied biology and therapeutics, in: C. Toothill (Ed.) Lysosomes in biology and pathology, Headington Hill Hall, 1981, pp. 74-74.
  81. [140] I.M. Tucker, J.C.W. Corbett, J. Fatkin, R.O. Jack, M. Kaszuba, B. MacCreath, F. McNeilWatson, Laser Doppler Electrophoresis applied to colloids and surfaces, Colloids and Surfaces: A, 20 (2015) 215-226.
  82. [134] P.K. Smith, R.I. Krohn, G.T. Hermanson, A.K. Mallia, F.H. Gartner, M.D. Provenzano, E.K. Fujimoto, N.M. Goeke, B.J. Olson, D.C. Klenk, Measurement of protein using bicinchoninic acid, Anal Biochem, 150 (1985) 76-85.
  83. [36] J. Wilschut, D. Hoekstra, Membrane fusion: lipid vesicles as a model system, Chem Phys Lipids, 40 (1986) 145-166.
  84. [154] A.L. Parker, D. Oupicky, P.R. Dash, L.W. Seymour, Methodologies for monitoring nanoparticle formation by self-assembly of DNA with poly(l-lysine), Anal Biochem, 302 (2002) 75-80.
  85. [109] N. Nomikou, A.P. McHale, Microbubble-enhanced ultrasound-mediated gene transfer-- towards the development of targeted gene therapy for cancer, Int J Hyperthermia, 28 (2012) 300-310.
  86. [50] J. Smisterova, A. Wagenaar, M.C. Stuart, E. Polushkin, G. ten Brinke, R. Hulst, J.B. Engberts, D. Hoekstra, Molecular shape of the cationic lipid controls the structure of cationic lipid/dioleylphosphatidylethanolamine-DNA complexes and the efficiency of gene delivery, J Biol Chem, 276 (2001) 47615-47622.
  87. [20] M.N.V.R. Kumar, U. Bakowsky, C.M. Lehr, Nanoparticles as Non-Viral Transfection Agents, in: Nanobiotechnology, Wiley-VCH Verlag GmbH & Co. KGaA, 2005, pp. 319- 342.
  88. [116] B.d. Kruijff, P.R. Cullis, A.J. Verkleij, Non-bilayer lipid structures in model and biological membranes, Trends in Biochemical Sciences, 5 (1980) 79-81.
  89. [22] I.S. Zuhorn, U. Bakowsky, E. Polushkin, W.H. Visser, M.C.A. Stuart, J.B.F.N. Engberts, D. Hoekstra, Nonbilayer phase of lipoplex-membrane mixture determines endosomal escape of genetic cargo and transfection efficiency, Molecular Therapy, 11 (2005) 801-810.
  90. [100] D.E. FitzGerald, J.E. Drumm, Non-invasive measurement of human fetal circulation using ultrasound: a new method., (1977).
  91. [94] M.J. Shieh, C.L. Peng, P.J. Lou, C.H. Chiu, T.Y. Tsai, C.Y. Hsu, C.Y. Yeh, P.S. Lai, Nontoxic phototriggered gene transfection by PAMAM-porphyrin conjugates, J Control Release, 129 (2008) 200-206.
  92. [17] I. Slivac, D. Guay, M. Mangion, J. Champeil, B. Gaillet, Non-viral nucleic acid delivery methods, Expert Opin Biol Ther, 17 (2017) 105-118.
  93. [25] H. Yin, R.L. Kanasty, A.A. Eltoukhy, A.J. Vegas, J.R. Dorkin, D.G. Anderson, Non-viral vectors for gene-based therapy, Nature Reviews Genetics, 15 (2014) 541-555.
  94. [70] T. Merdan, J. Callahan, H. Petersen, K. Kunath, U. Bakowsky, P. Kopeckova, T. Kissel, J. Kopecek, Pegylated polyethylenimine-Fab' antibody fragment conjugates for targeted gene delivery to human ovarian carcinoma cells, Bioconjug Chem, 14 (2003) 989-996.
  95. [68] T. Merdan, K. Kunath, H. Petersen, U. Bakowsky, K.H. Voigt, J. Kopecek, T. Kissel, PEGylation of poly(ethylene imine) affects stability of complexes with plasmid DNA under in vivo conditions in a dose-dependent manner after intravenous injection into mice, Bioconjug Chem, 16 (2005) 785-792.
  96. [79] K. Regnström, E.G.E. Ragnarsson, M. Köping-Höggård, E. Torstensson, H. Nyblom, P. Artursson, PEI - a potent, but not harmless, mucosal immuno-stimulator of mixed T-helper cell response and FasL-mediated cell death in mice, Gene Therapy, 10 (2003) 1575-1583.
  97. [123] C.J. Edgell, C.C. McDonald, J.B. Graham, Permanent cell line expressing human factor VIII-related antigen established by hybridization, Proc Natl Acad Sci U S A, 80 (1983) 3734- 3737.
  98. [5] F.D. Ledley, Pharmaceutical approach to somatic gene therapy, Pharm Res, 13 (1996) 1595- 1614.
  99. [160] A.I. Ivanov, Pharmacological inhibition of endocytic pathways: is it specific enough to be useful?, Methods Mol Biol, 440 (2008) 15-33.
  100. [21] I.S. Zuhorn, V. Oberle, W.H. Visser, J. Engberts, U. Bakowsky, E. Polushkin, D. Hoekstra, Phase behavior of cationic amphiphiles and their mixtures with helper lipid influences lipoplex shape, DNA translocation, and transfection efficiency, Biophys J, 83 (2002) 2096-2108.
  101. [118] G. Bastiat, M. Lafleur, Phase Behavior of Palmitic Acid/Cholesterol/Cholesterol Sulfate Mixtures and Properties of the Derived Liposomes, The Journal of Physical Chemistry B, (2007).
  102. [90] P.K. Selbo, A. Hogset, L. Prasmickaite, K. Berg, Photochemical internalisation: a novel drug delivery system, Tumour Biol, 23 (2002) 103-112.
  103. [162] A. Hogset, L. Prasmickaite, P.K. Selbo, M. Hellum, B.O. Engesaeter, A. Bonsted, K. Berg, Photochemical internalisation in drug and gene delivery, Adv Drug Deliv Rev, 56 (2004) 95-115.
  104. [91] K. Berg, M. Folini, L. Prasmickaite, P.K. Selbo, A. Bonsted, B.O. Engesaeter, N. Zaffaroni, A. Weyergang, A. Dietze, G.M. Maelandsmo, E. Wagner, O.J. Norum, A. Hogset, Photochemical internalization: a new tool for drug delivery, Curr Pharm Biotechnol, 8 (2007) 362-372.
  105. [97] M. Folini, K. Berg, E. Millo, R. Villa, L. Prasmickaite, M.G. Daidone, U. Benatti, N. Zaffaroni, Photochemical internalization of a peptide nucleic acid targeting the catalytic subunit of human telomerase, Cancer Res, 63 (2003) 3490-3494.
  106. [92] K. Berg, A. Weyergang, L. Prasmickaite, A. Bonsted, A. Hogset, M.T. Strand, E. Wagner, P.K. Selbo, Photochemical internalization (PCI): a technology for drug delivery, Methods Mol Biol, 635 (2010) 133-145.
  107. [85] T.J. Dougherty, C.J. Gomer, B.W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan, Q. Peng, Photodynamic therapy, J Natl Cancer Inst, 90 (1998) 889-905.
  108. [84] D.E.J.G.J. Dolmans, D. Fukumura, R.K. Jain, Photodynamic therapy for cancer, Nature Reviews Cancer, 3 (2003) 380-387.
  109. [89] M.A. Biel, Photodynamic therapy of head and neck cancers, Methods Mol Biol, 635 (2010) 281-293.
  110. [96] P. Shum, J.M. Kim, D.H. Thompson, Phototriggering of liposomal drug delivery systems, Adv Drug Deliv Rev, 53 (2001) 273-284.
  111. [108] A. Rahim, S.L. Taylor, N.L. Bush, G.R. ter Haar, J.C. Bamber, C.D. Porter, Physical parameters affecting ultrasound/microbubble-mediated gene delivery efficiency in vitro, Ultrasound Med Biol, 32 (2006) 1269-1279.
  112. [64] C. Brus, H. Petersen, A. Aigner, F. Czubayko, T. Kissel, Physicochemical and biological characterization of polyethylenimine-graft-poly(ethylene glycol) block copolymers as a delivery system for oligonucleotides and ribozymes, Bioconjug Chem, 15 (2004) 677-684.
  113. [153] H. Engelberg, Plasma heparin levels. Correlation with serum cholesterol and low-density lipoproteins, Circulation, 23 (1961) 573-577.
  114. [167] D.J. Gary, N. Puri, Y.Y. Won, Polymer-based siRNA delivery: perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery, J Control Release, 121 (2007) 64-73.
  115. [11] A. Fire, S. Xu, M.K. Montgomery, S.A. Kostas, S.E. Driver, C.C. Mello, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans, Nature, 391 (1998) 806-811.
  116. [74] J. Haas, M.N. Ravi Kumar, G. Borchard, U. Bakowsky, C.M. Lehr, Preparation and characterization of chitosan and trimethyl-chitosan-modified poly-(epsilon-caprolactone) nanoparticles as DNA carriers, AAPS PharmSciTech, 6 (2005) E22-30.
  117. [15] M. Amarzguioui, J.J. Rossi, Principles of Dicer substrate (D-siRNA) design and function, Methods Mol Biol, 442 (2008) 3-10.
  118. [81] E. Blanco, H. Shen, M. Ferrari, Principles of nanoparticle design for overcoming biological barriers to drug delivery, Nature Biotechnology, 33 (2015) 941-951.
  119. [23] M. Morille, C. Passirani, A. Vonarbourg, A. Clavreul, J.P. Benoit, Progress in developing cationic vectors for non-viral systemic gene therapy against cancer, Biomaterials, 29 (2008) 3477-3496.
  120. [157] A. Raup, V. Jérôme, R. Freitag, C.V. Synatschke, A.H.E. Müller, Promoter, transgene, and cell line effects in the transfection of mammalian cells using PDMAEMA-based nano-stars, Biotechnology Reports, 11 (2016) 53-61.
  121. [131] V. Bonasera, S. Alberti, A. Sacchetti, Protocol for high-sensitivity/long linear-range spectrofluorimetric DNA quantification using ethidium bromide, Biotechniques, 43 (2007) 173-174, 176.
  122. [136] T. Mosmann, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, 65 (1983) 55-63.
  123. [60] M. Neu, D. Fischer, T. Kissel, Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives, J Gene Med, 7 (2005) 992-1009.
  124. [143] M.J. Hope, R. Nayar, L.D. Mayer, P.R. Cullis, Reduction of Liposome Size and Preparation of Unilamellar Vesicles by Extrusion Techniques, in: G. Gregoriadis (Ed.) Liposome Technology, CRC Press, 1993.
  125. [113] V. Kumar, R.S. Cotran, T. Collins, S.L. Robbins, Robbins Pathological Basis of Disease., 7th ed., WB Saunders, Philadelphia, PA, 1999.
  126. [39] I.M. Hafez, P.R. Cullis, Roles of lipid polymorphism in intracellular delivery, Adv Drug Deliv Rev, 47 (2001) 139-148.
  127. [141] D. Goula, J.S. Remy, P. Erbacher, M. Wasowicz, G. Levi, B. Abdallah, B.A. Demeneix, Size, diffusibility and transfection performance of linear PEI/DNA complexes in the mouse central nervous system, Gene Ther, 5 (1998) 712-717.
  128. [106] M. Joersbo, J. Brunstedt, Sonication: A new method for gene transfer to plants, Physiologia Plantarum, 85 (1992) 230-234.
  129. [53] D.Y. Kwoh, C.C. Coffin, C.P. Lollo, J. Jovenal, M.G. Banaszczyk, P. Mullen, A. Phillips, A. Amini, J. Fabrycki, R.M. Bartholomew, S.W. Brostoff, D.J. Carlo, Stabilization of poly-Llysine/DNA polyplexes for in vivo gene delivery to the liver, Biochim Biophys Acta, 1444 (1999) 171-190.
  130. [112] T. Collins, A. Williams, G.I. Johnston, J. Kim, R. Eddy, T. Shows, M.A. Gimbrone, Jr., M.P. Bevilacqua, Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1, J Biol Chem, 266 (1991) 2466-2473.
  131. [121] I.M. Klotz, G.P. Royer, I.S. Scarpa, Synthetic derivatives of polyethyleneimine with enzyme-like catalytic activity (synzymes), Proc Natl Acad Sci U S A, 68 (1971) 263-264.
  132. [14] D.-H. Kim, M.A. Behlke, S.D. Rose, M.-S. Chang, S. Choi, J.J. Rossi, Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy, Nature Biotechnology, 23 (2004) 222- 226.
  133. [46] C.R. Dass, P.F. Choong, Targeting of small molecule anticancer drugs to the tumour and its vasculature using cationic liposomes: lessons from gene therapy, in: Cancer Cell Int, 2006, pp. 17.
  134. [168] S.R. Barthel, J.D. Gavino, L. Descheny, C.J. Dimitroff, Targeting selectins and selectin ligands in inflammation and cancer, Expert Opin Ther Targets, 11 (2007) 1473-1491.
  135. [165] G. ter Haar, Ultrasonic imaging: safety considerations, in: Interface Focus, 2011, pp. 686-697.
  136. [6] R.C. Mulligan, The basic science of gene therapy, Science, 260 (1993) 926-932.
  137. [82] A.P. Dabkowska, D.J. Barlow, A.V. Hughes, R.A. Campbell, P.J. Quinn, M.J. Lawrence, The effect of neutral helper lipids on the structure of cationic lipid monolayers, J R Soc Interface, 9 (2012) 548-561.
  138. [26] C. Kneuer, C. Ehrhardt, H. Bakowsky, M.N. Kumar, V. Oberle, C.M. Lehr, D. Hoekstra, U. Bakowsky, The influence of physicochemical parameters on the efficacy of non-viral DNA transfection complexes: a comparative study, J Nanosci Nanotechnol, 6 (2006) 2776-2782.
  139. [103] C. Olbrich, P. Hauff, F. Scholle, W. Schmidt, U. Bakowsky, A. Briel, M. Schirner, The in vitro stability of air-filled polybutylcyanoacrylate microparticles, Biomaterials, 27 (2006) 3549-3559.
  140. [57] R.V. Benjaminsen, M.A. Mattebjerg, J.R. Henriksen, S.M. Moghimi, T.L. Andresen, The possible "proton sponge " effect of polyethylenimine (PEI) does not include change in lysosomal pH, Mol Ther, 21 (2013) 149-157.
  141. [58] J.-P. Behr, The Proton Sponge: a Trick to Enter Cells the Viruses Did Not Exploit, (1997).
  142. [51] H. Farhood, N. Serbina, L. Huang, The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer, Biochim Biophys Acta, 1235 (1995) 289-295.
  143. [101] P. Freeman, The role of ultrasound in the assessment of the trauma patient, Aust J Rural Health, 7 (1999) 85-89.
  144. [3] D.M. Dykxhoorn, D. Palliser, J. Lieberman, The silent treatment: siRNAs as small molecule drugs, Gene Ther, 13 (2006) 541-552.
  145. [47] H. Lv, S. Zhang, B. Wang, S. Cui, J. Yan, Toxicity of cationic lipids and cationic polymers in gene delivery, J Control Release, 114 (2006) 100-109.
  146. [156] M. Emerson, L. Renwick, S. Tate, S. Rhind, E. Milne, H.A. Painter, A.C. Boyd, G. McLachlan, U. Griesenbach, S.H. Cheng, D.R. Gill, S.C. Hyde, A. Baker, E.W. Alton, D.J. Porteous, D.D. Collie, Transfection efficiency and toxicity following delivery of naked plasmid DNA and cationic lipid-DNA complexes to ovine lung segments, Mol Ther, 8 (2003) 646-653.
  147. [24] K. Tabatt, C. Kneuer, M. Sameti, C. Olbrich, R.H. Muller, C.M. Lehr, U. Bakowsky, Transfection with different colloidal systems: comparison of solid lipid nanoparticles and liposomes, J Control Release, 97 (2004) 321-332.
  148. [122] S. Fiedler, R. Wirth, Transformation of bacteria with plasmid DNA by electroporation, Anal Biochem, 170 (1988) 38-44.
  149. [71] O.M. Merkel, M.A. Mintzer, J. Sitterberg, U. Bakowsky, E.E. Simanek, T. Kissel, Triazine dendrimers as non-viral gene delivery systems: Effects of molecular structure on biological activity, Bioconjug Chem, 20 (2009) 1799-1806.
  150. [138] R. Duncan, M. Bhakoo, M.-L. Riley, A. Tuboku-Metzger, Soluble Polymeric Drug Carriers: Haematocompatibility, Birkhäuser, Basel, 1991.
  151. [102] W.G. Pitt, G.A. Husseini, B.J. Staples, Ultrasonic Drug Delivery - A General Review, Expert Opin Drug Deliv, 1 (2004) 37-56.
  152. [133] L. Duse, Untersuchungen einer Prototyp LED-Leuchte zur Photodynamischen Therapie mit photosensibilisator-haltigen Liposomen, in: Department of Pharmaceutics and Biopharmaceutics, Technische Hochschule Mittelhessen, Gießen, 2016.
  153. [177] J.G. Lenahan, S. Frye, G.E. Phillips, Use of the Activated Partial Thromboplastin Time in the Control of Heparin Administration, Clinical Chemistry, 12 (1966) 263-268.
  154. [176] G.E. Deibler, M.S. Holmes, P.L. Campbell, J. Gans, Use of triton X-100 as a hemolytic agent in the spectrophotometric measurement of blood O2 saturation, J Appl Physiol, 14 (1959) 133-136.
  155. [152] J. Sitterberg, A. Ozcetin, C. Ehrhardt, U. Bakowsky, Utilising atomic force microscopy for the characterisation of nanoscale drug delivery systems, Eur J Pharm Biopharm, 74 (2010) 2-13.
  156. [86] F. Stewart, P. Baas, W. Star, What does photodynamic therapy have to offer radiation oncologists (or their cancer patients)?, Radiother Oncol, 48 (1998) 233-248.
  157. [137] M. Wintrobe, Wintrobe's Clinical Hematology, 9 ed., Lea & Febiger, Philadelphia, 1993.


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