Tell me something I do not know. Multiscale molecular modeling of dendrimer/ dendron organization and self-assembly in gene therapy

Current Medicinal Chemistry

Volumn 19, Issue 29, 2012, Pages 5062-5087

  Posocco, P ^a   Laurini, E ^a   Dal Col, V ^a   Marson, D ^a   Karatasos, K ^b   Fermeglia, M ^a   Pricl, S ^a  

^a UNIVERSITY OF TRIESTE   (Italy)

^b ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

Author keywords

Dendrimers; Dendrons; Gene therapy; Multiscale molecular modeling; Self assembly

Indexed keywords

DENDRIMER; DENDRON; DNA; HEPARIN; NANOCARRIER; NANOPARTICLE; NUCLEIC ACID; POLYMER; RNA; UNCLASSIFIED DRUG;

CHEMICAL STRUCTURE; DENSITY; GENE DELIVERY SYSTEM; GENE THERAPY; MOLECULAR DYNAMICS; MOLECULAR MECHANICS; MOLECULAR MODEL; MOLECULAR RECOGNITION; NANOMEDICINE; NANOTECHNOLOGY; PH; QUANTUM MECHANICS; REVIEW; STATIC ELECTRICITY; STRUCTURE ACTIVITY RELATION;

DENDRIMERS; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; HUMANS; MICELLES; MODELS, MOLECULAR;

EID: 84870436140     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867311209025062     Document Type: Review

References (99)

1. (a) Watts, J.K.; Corey, D.R. Silencing disease genes in the laboratory and the clinic. J. Pathol., 2012, 226(2), 365-379;
2. (b) Both, G.; Alexander, I.; Fletcher,S.; Nicolson, T.J.; Rasko, J.E.; Wilton, S.D.; Symonds, G. Gene therapy: therapeutic applications and relevance to pathology. Pathology, 2011, 43(6), 642-656;
3. (c) Gambari.; R.; Fabbri, E.; Borgatti, M.; Lampronti, I.; Finotti, A.; Brognara, E.; Bianchi, N.; Manicardi, A.; Marchelli, R.; Corradini, R. Targeting microRNAs involved in human diseases: a novel approach for modification of gene expression and drug development. Biochem. Pharmacol., 2011, 82(10), 1416-1429;
4. (d) G.C. Shukla; F. Haque; Y. Tor; L.M. Wilhelmsson; J.J. Toulmé; H. Isambert; P. Guo; J.J. Rossi; S. A. Tenenbaum; B.A. Shapiro. A boost for the emerging field of RNA nanotechnology. ACS Nano, 2011, 5(5), 3405-3418., and references therein.
5. Ruenraroengsak, P.; Cook, J.M.; Florence, A.T. Nanosystem drug targeting: Facing up complex realities. J. Control. Release, 2010, 141(3), 265-276.
6. Reischl, D.; Zimmer. A. Drug delivery of siRNA therapeutics: potentials and limits of nanosystems. Nanomedicine: Nanotech. Biol. Med., 2009, 5(1), 8-20.
7. Juliano, R.; Alam, R.; Dixit, V.; Kang, H. Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides. Nucl. Acid Res., 2008, 36(12), 4158-4171.
8. (a) Behr, J.P. Synthetic gene transfer vectors II: back to the future. Acc. Chem. Res., Article ASAP, Publication Date (Web): February 6, 2012, DOI: 10.1021/ar200213g;
9. (b) Mintzer, M.A.; Simanek, E.E. Nonviral vectors for gene delivery. Chem. Rev., 2009, 109(2), 259-302;
10. c) Jeong, J.H.; Kim, S.W.; Park, T.G. molecular design of functional polymers for gene therapy. Progr. Polym. Sci. 2007, 32(11), 1239-1274.
11. a) Wang, M.; Thanou, M. Targeting nanoparticles to cancer. Pharm. Res., 2010, 62(1), 90-99;
12. b) Mishra, B.; Patel, B.B.; Tiwari, S. Colloidal nanocarriers: a review on formulation technology, types, and applications toward drug delivery. Nanomedicine: Nanotech. Biol. Med., 2010, 6(1), 9-24;
13. c) de Martinprey, H.; Vauthier, C.; Malvy, C.; Couvreur, P. Polymer nanocarriers for the delivery of small fragments of nucleic acids: oligonucleotides and siRNA. Eur. J. Pharm. Biopharm., 2009, 71(3), 490-504;
14. d) Christian, D.A.; Cai, S.; Bowen, D.M.; Kim, Y.; Pajerowski, D.; Discher, D.E. Polymersome carriers: from self-assembly to siRNA and protein therapeutics. Eur. J. Pharm. Biopharm., 2009, 71(3), 463-467;
15. e) Ferrari, M. Nanovector therapeutics. Curr. Opin. Chem. Biol., 2005, 9(4), 343-346;
16. f) Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer, 2005, 5(3), 161-71.
17. a) Sakamoto, J.H.; van de Ven, A.L.; Godin, B.; Blanco, E.; Serda, R.E.; Grattoni, A., et al. Enabling individualized therapy through nanotechnology. Pharmacol. Res., 2010, 62(2), 57-89;
18. b) Singh, R.; Lillard, J.W. Nanoparticle-based targeted drug delivery. Exp. Mol. Pathol., 2009, 86(3), 215-223.
19. Posocco, P.; Fermeglia, M.; Pricl, S. Morphology prediction of block copolymers for drug delivery by mesoscale simulations. J. Mater. Chem., 2010, 20, 7742-7753.
20. a) Tomalia, D.A. A new class of polymers: starburst-dendritic macromolecules. Polym. J., 1985, 17, 117-132.
21. Lee, C.C.; MacKay, J.A.; Frechet, J.M.; Szoka, F.C. Designing dendrimers for biological applications. Nat. Biotechnol., 2005, 23(12), 1517-1526.
22. Tomalia, D.A.; Naylor, A.M.; Goddard, W.A. III. Starburst dendrimers: molecular-level control of size, shape, surface shemistry, topology, and flexibility from atoms to macroscopic matter. Angew. Chem. Int. Ed. Engl., 1990, 29(2), 138-175.
23. Svenson, S. Dendrimers as versatile platform in drug delivery applications. Eur. J. Pharm. Biopharm., 2009, 71(3), 445-462.
24. Liu, M.; Frechet, J.M. designing dendrimers for drug delivery. Pharm. Sci. Technol. Today, 1999; 2(10), 393-401.
25. a) Cheng, Y.; Zhao, L.; Li, Y.; Xu, T. Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives. Chem. Soc. Rev., 2011, 40, 2673-2703;
26. b) Medina, S.H.; El-Sayed, M.E.H. Dendrimers as carriers for delivery of chemotherapeutic agents. Chem. Rev., 2009, 109(7), 3141-3157;
27. c) Tekade R.K.; Kumar, P.V.; Jain, N.K. Dendrimers in oncology: an expanding horizon. Chem. Rev., 2009, 109(1), 49-87;
28. d) Rolland, O.; Turrin, C.O.; Caminade, A.M.; Majoral, J.P. Dendrimers and nanomedicine: multivalency in action. New J. Chem. 2009, 33, 1809-1824.
29. National science and Technology Council Committee on Technology. The National Nanotechnology Initiative: research and development leading to a revolution in technology and industry. Washington DC: Office of Science and Technology Policy, 2005.
30. Koo, O.; Rubinstein, I.; Onyuksel, H. Role of nanotechnology in target drug delivery and imaging: a concise review. Nanomedicine: Nanotech. Biol. Med., 2005, 1(3), 193-212.
31. a) Toth, R.; Santese, F.; Pereira, S.P.; Nieto, D.R.; Pricl, S.; Fermeglia, M.; Posocco, P. Size and shape matter! A multiscale molecular simulation approach to polymer nanocomposites. J. Mater. Chem., First published on the web: 07 Feb 2012, doi: 10.1039/C2JM15763B;
32. b) Posocco, P.; Fermeglia, M.; Pricl, S. Morphology prediction of block copolymers for drug delivery by mesoscale simulations. J. Mater. Chem., 2010, 20, 7742-7753;
33. c) Scocchi, G.; Posocco, P.; Handgraaf, J.-W.; Fraaije, J.G.; Fermeglia, M.; Pricl, S. A complete multiscale modeling approach for polymer-clay nanocomposites. Chem. Eur. J., 2009, 15(31), 7586-7592;
34. d) Toth, R.; Voorn, D.-J; Handgraaf, J.-W.; Fraaije, J.G.E.M.; Fermeglia, M.; Pricl, S.; Posocco, P. Macromolecules, 2009, 42(21), 8260-8270;
35. e) Fermeglia, M.; Pricl, S. Computers & Chem. Eng., 2009, 33, 1701-1710 and references therein.
36. a) Hoogerbrugge, P.J.; Koelman, J.M.V.A. Simulating microscopic hydrodynamic phenomena with dissipative particle dynamics. Europhys. Lett., 1992, 19(3), 155-160;
37. b) Español, P.; Warren, P.B. Statistical mechanics of dissipative particle dynamics. Europhys. Lett., 1995, 30(4), 191-196;
38. c) Groot, R.D.; Warren, P.B. Dissipative particle dynamics: bridging the gap between atomistic and mesoscopic simulation. J. Chem. Phys., 1997, 107(11), 4423-4435.
39. Tang, M.X.; Redemann, C.T.; Szoka, F.C. In vitro gene delivery by degraded polyamidoamine dendrimers. Bioconjugate Chem. 1996, 7(6), 703-714.
40. Sonawane, N.D.; Szoka, F.C., Verkman, A.S. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA poly-plexes. J. Biol. Chem., 2003, 278(45), 44826-44831.
41. a) Liu, X.X.; Rocchi, P.; Qu, F.; Zheng, S.; Liang, Z.C.; Gleave, M.; Iovanna, J.; Peng, L. PAMAM dendrimers mediate siRNA delivery to target Hsp27 and produce potent antiproliferative effects on prostate cancer cells. ChemMedChem, 2009, 4(8), 1302-1310;
42. b) Shen, X.C.; Zhou, J.; Liu, X.X.; Wu, J.; Qu, F.; Zhang, Z.L.; Pang, D.W.; Quelever, G.; Zhang, C.C.; Peng, L. Importance of size-to-charge ratio in the construction of stable and uniform nanoscale RNA/dendrimer complexes. Org. Biomol. Chem., 2007, 5, 3674-3681;
43. c) Zhou, J.; Wu, J.; Hafdi, N.; Behr, J.P.; Erbacher, P., Peng, L. PAMAM dendrimers for efficient siRNA delivery and potent gene silencing. Chem. Commun., 2006, 2362-2364;
44. d) Wu, J.; Zhou, J.; Qu, F.; Bao, P.; Zhang, Y.; Peng, L. Polycationic dendrimers interact with RNA molecules: polyamine dendrimers inhibit the catalytic of Candida ribozymes. Chem. Commun., 2005, 313-315.
45. a) Posocco, P.; Ferrone, M.; Fermeglia, M.; Pricl, S. Binding at the core. Computational study of structural and ligand binding properties of naphthiridine based dendrimers. Macromolecules, 2007, 40(6), 2257-2266;
46. b) Metullio, L.; Ferrone, M.; Coslanich, A.; Fuchs, S.; Fermeglia, M.; Paneni, M.S.; Pricl, S. Polyamidoamine (yet not PAMAM) dendrimers as bioinspired materials for drug delivery: structure-activity relationships by molecular simulations. Biomacromolecules, 2004, 5(8), 1371-1378;
47. c) Pricl, S.; Fermeglia, M.; Ferrone, M.; Asquini, A. Scaling properties in the molecular structure of three-dimensional, nanosized phenylene-based dendrimers as studied by atomistic molecular dynamics simulations. Carbon, 2003, 41(12), 2269-2283;
48. d) Fermeglia, M.; Ferrone, M.; Pricl, S. Computer-aided simulation of a dendrimer with a protoporphyrinic core as potential, novel hemoprotein mimic. Bioorg. Med. Chem., 2002, 10(12), 2471-2478;
49. e) Tomalia, D.A.; Uppuluri, S.; Swanson, D.R.; Li, J. Dendrimers as reactive modules for the synthesis of new structure-controlled, higher-complexity megamers. Pure Appl. Chem., 2000, 72(12), 2343-2358.
50. Liu, X.X.; Wu, J.; Yammine, M.; Zhou, J.; Posocco, P.; Viel, S.; Liu, C.; Ziarelli, F.; Fermeglia, M.; Pricl, S.; Victorero, G.; Nguyen, C.; Erbacher, P.; Behr, J.P.; Peng, L. Structurally flexible triethanolamine core PAMAM dendrimers are effective nanovectors for DNA transfection in vitro and in vivo to the mouse thymus. Bioconjug. Chem., 2011, 22(12), 2461-2473.
51. Karatasos, K.; Posocco, P.; Laurini, E.; Pricl, S. Poly(amidoamine)-based dendrimer/siRNA complexation studied by computer simulations: effects of pH and generation on dendrimer structure and siRNA binding. Macromol Biosci., 2012, 12(2), 225-240.
52. Huissmann, S.; Likos, C.N.; Blaak, R. Conformations of high-generation dendritic polyelectrolytes. J. Mater. Chem., 2010, 20, 10486-10494;
53. b) Karatasos, K.; Adolf, D.B.; Davies, G.R. Statics and dynamics of model dendrimers as studied by molecular dynamics simulations. J. Chem. Phys., 2001, 115, 5310-5318.
54. Fant, K.; Esbjorner, E.K.; Lincoln, P.; Norden, B. DNA condensation by PAMAM dendrimers: self-assembly characteristics and effect on transcription. Biochemistry, 2008, 47(6), 1732-1740.
55. Bielinska, A.U.; Kukowska-Latallo, J.F.; Baker, J.J. The interaction of plasmid DNA with polyamidoamine dendrimers: mechanism of complex formation and analysis of alterations induced in nuclease sensitivity and transcriptional activity of the complexed DNA. Biochim. Biophys. Acta, 1997, 1353(2), 180-190.
56. Gary, D.; Pury, N.; Won, Y. Polymer-based siRNA delivery: perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery, J. Control. Release, 2007, 121(1-2), 64-73.
57. Bolcato-Bellemin, A. L.; Bonnet, M. E.; Creusat, G.; Erbacher, P.; Behr, J. P. Sticky overhangs enhance siRNA-mediated gene silencing. Proc. Natl. Acad. Sci. U.S.A., 2007, 104(41), 16050-16055.
58. Liu, X.; Liu, C.; Laurini, E.; Posocco, P.; Pricl, S.; Qu, F.; Rocchi, P.; Peng, L. Efficient delivery of sticky siRNA and potent gene silencing in a prostate cancer model using a generation 5 triethanolamine-core PAMAM dendrimer. Mol. Pharm., Article ASAP, Publication Date (Web): December 30, 2011, doi:10.1021/mp2006104.
59. a) Gomez-Casado, A.; Dam, H.H.; Yilmaz, M.D.; Florea, S.; Jonkheijm; P.; Huskens, J. Probing multivalent interactions in a synthetic host-guest complex by dynamic force spectroscopy. J. Am. Chem. Soc., 2011, 133(28), 10849-10857;
60. b) Kane, R.S. Thermodynamics of Multivalent Interactions: Influence of the linker. Langmuir, 2010, 26(11), 8636-8640;
61. c) Free energy balance predicated dendrimer binding multivalency at molecular printboards. Langmuir, 2007, 23(16), 8441-8451;
62. d) Badjic, J.D.; Nelson, A.; Cantrill, S.J.; Turnbull, W.B.; Stoddard, J.F. Multivalency and Cooperativity in Supramolecular Chemistry. Acc. Chem. Res. 2005, 38(9), 723-732;
63. e) Huskens, J.; mulder, A.; Auletta, T.; Nijhuis, C.A.; Ludden, M.J.W.; Reinhoudt, D.N. A model for describing the thermodynamics of multivalent host-guest interactions at interfaces. J. Am. Chem. Soc., 2004, 126(21), 6784-6797;
64. f) Christensen, T.; Gooden, D.M.; Kung, J.E.; Toone, E.J. Additivity and the physical basis of multivalency effects: a thermodynamic investigation of the Calcium EDTA interaction. J. Am. Chem. Soc., 2003, 125(24), 7357-7366;
65. g) Kitov, P.I.; Bundle, D.R. On the nature of the multivalence effect: a thermodynamic model. J. Am. Chem. Soc., 2003, 125(52), 16271-16284.
66. Rosen, B.M.; Wilson, C.J.; Wilson, D.A.; Peterca, M.; Imam, M.R.; Percec, V. Dendron-mediated self-Assembly, disassembly, and self-organization of complex systems. Chem. Rev., 2009, 109(11), 6275-6540.
67. Smith, D.K.; Hirst, A.R.; Love, C.S.; Hardy, J.G.; Brignell, S.V.; Huang, B. Self-assembly using dendritic building blocks - towards controllable nanomaterials. Prog. Polym. Sci., 2005, 30(3-4), 220-293.
68. a) Hamley, J.W. nanotechnology with soft materials. Angew. Chem. Int. Ed., 2003, 42(15), 1692-1712;
69. b) Whitesides, G.M.; Grzybowski, B. Selfassembly at all scales. Science, 2002, 295(5564), 2418-2421.
70. a) Steed, J.W.; Atwood, J.L. Supramolecular Chemistry. Wiley & Sons: Chichester, 2000;
71. b) Beer, P.D.; Gale, P.A., Smith, D.K. Supramolecular Chemistry. Oxford University Press: Oxford, 1999.
72. a) Smith, D.K. Recent developments in dendrimer chemistry. Tetrahedron, 2003, 59(22), 3797-3798;
73. b) Smith, D.K.; Diederich, F. Supramolecular dendrimer chemistry: a journey through the branched architecture. Top. Curr. Chem., 2000, 210, 183-227.
74. Jones, S.P.; Gabrielson, N.P.; Pack, D.W.; Smith, D.K. Synergistic effects in gene delivery -a structure-activity approach to the optimisation of hybrid dendritic-lipidic transfection agents. Chem. Commun., 2008, 4700-4702.
75. Posocco, P.; Pricl, S.; Jones, S.P.; Barnard, A.; Smith, D.K. Less is more - multiscale modeling of self-assembling multivalency and its impact on DNA binding and gene delivery. Chem. Sci., 2010, 1, 393-404.
76. Jones, S.P.; Pavan, G.M.; Danani, A.; Pricl, S.; Smith, D.K. Quantifying the effect of surface ligands on dendron-DNA interactions: insights into multivalency through a combined experimental and theoretical approach. Chem. Eur. J., 2010, 16(15), 4519-4532.
77. Pavan, G.M.; Danani, A.; Pricl, S.; Smith, D.K. Modeling the multivalent recognition between dendritic molecules and DNA: understanding how ligand "sacrifice" and screening can enhance binding. J. Am. Chem. Soc., 2009, 131(28), 9686-9694.
78. (a) Israelachvili, J.N.; Mitchell, D.J.; Ninham, B.W. Theory of self-assembly of lipid bilayers and vesicles. Biochim. Biophys. Acta, Biomembr., 1977, 470(2), 185-201;
79. b) Israelachvili, J.N.; Mitchell, D.J.; Ninham, B.W. Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers. J. Chem. Soc., Faraday Trans. II, 1976, 72(2), 1525-1568.
80. Jones, S.P.; Gabrielson, N.P.; Wong, C.H.; Chow, H.F.; Pack, D.W.; Posocco, P.; Fermeglia, M.; Pricl, S.; Smith, D.K. Hydrophobically modified dendrons: developing structure-activity relationships for DNA binding and gene transfection. Mol Pharm., 2011, 8(2), 416-429.
81. Abdelhady, H.G.; Allen, S.; Davies, M.C.; Roberts, C.J.; Tendler, S.J.B.; Williams, P.M. Direct real-time molecular scale visualization of the degradation of condensed DNA complexed exposed to DNase I. Nucleic Acid Res., 2003, 31(14), 4001-4005.
82. a) Dorigo, B.; Schalch, T.; Kulangara, A.; Duda, S.; Schroeder, R.; Richmond, T.J. Nucleosome arrays reveal the two-start organization of the chromatin fibers. Science, 2004, 306(5701), 1571-1573;
83. b) Olins, A.L.; Olins, D.E. Spheroid chromatin units. Science, 1974, 183(4122), 330-332.
84. Marenduzzo, D.; Finan, K.; Cook, P.R. The depletion attraction: an underappreciated force driving cellular organization. J. Cell. Biol., 2006, 175(5), 681-686.
85. Manning, G.S. Limiting laws and counterion condensation in polyelectrolyte solution. J. Chem. Phys., 1969, 51(3), 924-933.
86. (a) May, S., Ben-Shaul, A. Modeling of cationic lipid-DNA complexes. Curr. Med. Chem., 2004, 11(2), 151-167;
87. b) Harries, D.; May, S.; Gelbart, W.M.; Ben-Shaul, A. Structure, stability, and thermodynamics of lamellar DNA-lipid complexes. Biophys. J., 1998, 75(1), 159-173;
88. c) Bruinsma, R. Electrostatics of DNA cationic lipid complexes: isoelectric instability. Eur. Phys. J., 1998, B4, 75-78.
89. Tanford, C. The hydrophobic effect: formation of micelles and biological membranes, 2nd ed. Krieger Publishing Co., Malabar, FL, 1991.
90. (a) Patrickios, C.S. Micellization model for multivalent ionic surfactants. J. Phys. Chem., 1995, 99(48), 17437-17441;
91. (b) Nagarajan, R. Molecular packing parameter and surfactant self-assembly: the neglected role of the surfactant tail. Langmuir, 2002, 18(1), 31-38.
92. Tomas, S.; Milanesi, L. Hydrophobically self-assembled nanoparticles as molecular receptors in water. J. Am. Chem. Soc., 2009, 131(18), 6618-6623.
93. a) Sella, E.; Shabat, D. Chem. Commun., 2008, 5701-5703;
94. b) Sagi, A.; Segal, E.; Satchi-Fainaro, R.; Shabat, D. Bioorg. Med. Chem., 2007, 15(11), 3720-3727;
95. c) Perry, R.; Amir, R.J.; Shabat, D. New J. Chem., 2007, 31, 1307-1312;
96. d). Kevwitch, R.M.; McGrath, D.V. New J. Chem., 2007, 31, 1332-1336, and references therein.
97. Kostiainen, M.A.; Smith, D.K.; Ikkala, O. Angew. Chem. Int. Ed., 2007, 46, 7600-7604.
98. Welsh, D.J.; Jones, S.P.; Smith, D.K. Angew. Chem. Int. Ed., 2009, 48, 4047-4050.
99. Barnard, A.; Posocco, P.; Pricl, S.; Calderon, M.; Haag, R.; Hwang, M.E.; Shum, V.W.; Pack, D.W.; Smith, D.K. Degradable self-assembling dendrons for gene delivery: experimental and theoretical insights into the barriers to cellular uptake. J. Am. Chem. Soc., 2011, 133(50),20288-20300.