Skip to main content

Polyelectrolyte Complexes of DNA and Polycations as Gene Delivery Vectors

  • Chapter
  • First Online:

Part of the book series: Advances in Polymer Science ((POLYMER,volume 256))

Abstract

This review gives representative examples of the various types of synthetic cationic polymers or polyampholytes (chemical structure, architecture, etc) that can be used to complex DNA (forming polyplexes) for their application in gene delivery. In designing polycations for gene delivery, one has to take into account a balance between protection of DNA versus loss of efficiency for DNA condensation and efficient condensation versus hindering of DNA release. Indeed, if the polyplexes are not stable enough, premature dissociation will occur before delivery of the genetic material at the desired place, resulting in low transfection efficiency; on the other hand, a complex that is too stable will not release the DNA, also resulting in low gene expression. The techniques generally used to determine these properties are gel electrophoresis to test the DNA/polymer complexation, ethidium bromide or polyanion displacement to test the affinity of a polymer for DNA, and light scattering to determine the extent of DNA condensation. Moreover, with the development of more precise instruments for physico-chemical characterization and appropriate biochemical and biophysical techniques, a direct link between the physico-chemical characteristics of the polyplexes and their in vitro and in vivo properties can be drawn, thus allowing tremendous progress in the quest towards application of polyplexes for gene therapy, beyond the research laboratory.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

AFM:

Atomic force microscopy

Arg:

Arginine

bp:

Base pair

CAC:

Critical aggregation concentration

CMC:

Critical micelle concentration

CMV:

Cytomegalovirus

COS (cells):

CV-1 (simian) cell line carrying the SV40 genetic material

ctDNA:

Calf thymus DNA

Da:

Dalton, g.mol−1

DLS:

Dynamic light scattering

DLVO:

Derjaguin, Landau, Verwey, and Overbeek theory

DNA:

Deoxyribonucleic acid

DP:

Degree of polymerization

ds:

Double stranded

EGFP:

Enhanced green fluorescent protein

EM:

Electron microscopy

EtBr:

Ethidium bromide

Glu:

Glutamic acid

HEK (cells):

Human embryonic kidney cell line

HepG2 (cells):

Human hepatocarcinoma cell line with epithelial morphology

His:

Histidine

HIV:

Human immunodeficiency virus

IPEC:

Interpolylectrolyte complex

LPEI:

Linear polyethyleneimine

LS:

Light scattering

Luc:

Luciferase

Lys:

Lysine

MPC:

2-Methacryloxyethyl phosphorylcholine

MPS:

Mononuclear phagocyte system

NCP:

Nucleosome core particle

NMR:

Nuclear magnetic resonance

PAMAM:

Poly(amido amine)

PCL:

Poly(ε-caprolactone)

PDI:

Polydispersity index

PDMAEMA:

Poly[(2-dimethylamino) ethyl methacrylate]

pDNA:

Plasmid DNA

PEC:

Polyelectrolyte complex

PEG:

Poly(ethylene glycol)

PEI:

Polyethyleneimine

PHEMA:

Poly(2-hydroxy ethyl methacrylate)

PHPMA:

Poly(2-hydroxy propyl methacrylate)

PLL:

Poly(l-lysine)

PLLA:

Poly(l-lactide)

PMMA:

Poly(methyl methacrylate)

PNIPAM:

Poly(N-isopropyl acrylamide)

PPI:

Poly(propylene imine)

PTMAEMA:

Poly[(N-trimethylammonium) ethyl methacrylate]

PVP:

Poly(4-vinylpyridine)

RNA:

Ribonucleic acid

SV:

Simian virus

TEM:

Transmission electron microscopy

References

  1. Kundu PP, Sharma V (2008) Synthetic polymeric vectors in gene therapy. Curr Opin Solid State Mater Sci 12:89–102

    CAS  Google Scholar 

  2. Wong SY, Pelet JM, Putnam D (2007) Polymer systems for gene delivery–past, present, and future. Prog Polym Sci 32:799–837

    CAS  Google Scholar 

  3. Dubruel P, Schacht E (2006) Vinyl polymers as non-viral gene delivery carriers: current status and prospects. Macromol Biosci 6:789–810

    CAS  Google Scholar 

  4. Kabanov AV, Felgner PL, Seymour LW (eds) (1998) Self-assembling complexes for gene delivery. Wiley, New York

    Google Scholar 

  5. Shcharbin DG, Klajnert B, Bryszewska M (2009) Dendrimers in gene transfection. Biochemistry 74:1070–1079

    CAS  Google Scholar 

  6. Dufès C, Uchegbu IF, Schätzlein AG (2005) Dendrimers in gene delivery. Adv Drug Deliv Rev 57:2177–2202

    Google Scholar 

  7. Ainalem M-L, Nylander T (2011) DNA condensation using cationic dendrimers–morphology and supramolecular structure of formed aggregates. Soft Matter 7:4577–4594

    CAS  Google Scholar 

  8. Guillot-Nieckowski M, Eisler S, Diederich F (2007) Dendritic vectors for gene transfection. New J Chem 31:1111–1127

    CAS  Google Scholar 

  9. Paleos CM, Tsiourvas D, Sideratou Z (2007) Molecular engineering of dendritic polymers and their application as drug and gene delivery systems. Mol Pharm 4:169–188

    CAS  Google Scholar 

  10. Fischer W, Calderón M, Haag R (2010) Hyperbranched polyamines for transfection. Top Curr Chem 296:95–129

    CAS  Google Scholar 

  11. Zhou Y, Huang W, Liu J, Zhu X, Yan D (2010) Self-assembly of hyperbranched polymers and its biomedical applications. Adv Mater 22:4567–4590

    CAS  Google Scholar 

  12. Nakayama Y (2012) Hyperbranched polymeric “star vectors” for effective DNA or siRNA delivery. Acc Chem Res 45:994–1004

    CAS  Google Scholar 

  13. Mao S, Sun W, Kissel T (2010) Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev 62:12–27

    CAS  Google Scholar 

  14. Azzam T, Domb AJ (2005) Cationic polysaccharides for gene delivery. In: Amiji MM (ed) Polymeric gene delivery–principles and applications. CRC, Boca Raton, pp 279–299

    Google Scholar 

  15. Yudovin-Farber I, Eliyahu H, Domb AJ (2007) Cationic polysaccharides for DNA delivery. In: Friedmann T, Rossi J (eds) Gene transfer: delivery and expression of DNA and RNA, a laboratory manual. CSHL, Cold Spring Harbor, pp 507–513

    Google Scholar 

  16. Froehlich T, Wagner E (2010) Peptide- and polymer-based delivery of therapeutic RNA. Soft Matter 6:226–234

    CAS  Google Scholar 

  17. Osada K, Kataoka K (2006) Drug and gene delivery based on supramolecular assembly of PEG-polypeptide hybrid block copolymers. Adv Polym Sci 202:113–153

    CAS  Google Scholar 

  18. Kircheis R, Wightman L, Wagner E (2001) Design and gene delivery activity of modified polyethylenimines. Adv Drug Deliv Rev 53:341–358

    CAS  Google Scholar 

  19. Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proc Natl Acad Sci USA 92:7297–7301

    CAS  Google Scholar 

  20. Kim SW (2007) Polylysine copolymers for gene delivery. In: Friedmann T, Rossi J (eds) Gene transfer: delivery and expression of DNA and RNA, a laboratory manual. CSHL, Cold Spring Harbor, pp 461–471

    Google Scholar 

  21. Turrin C-O, Caminade A-M (2011) Dendrimers as transfection agents. In: Caminade A-M (ed) Dendrimers. Wiley, New York, pp 413–435

    Google Scholar 

  22. Kubasiak LA, Tomalia DA (2005) Cationic dendrimers as gene transfection vectors: dendri-poly(amidoamines) and dendri-poly(propylenimines). In: Amiji MM (ed) Polymeric gene delivery–principles and applications. CRC, Boca Raton, pp 133–157

    Google Scholar 

  23. Smedt SCD, Demeester J, Hennink WE (2000) Cationic polymer based gene delivery systems. Pharm Res 17:113–126

    Google Scholar 

  24. Bertin A, Hermes F, Schlaad H (2010) Biohybrid and peptide-based polymer vesicles. Adv Polym Sci 224:167–195

    CAS  Google Scholar 

  25. Iatrou H, Frielinghaus H, Hanski S, Ferderigos N, Ruokolainen J, Ikkala O, Richter D, Mays J, Hadjichristidis N (2007) Architecturally induced multiresponsive vesicles from well-defined polypeptides. Formation of gene vehicles. Biomacromolecules 8:2173–2181

    CAS  Google Scholar 

  26. Ho PS, Carter M (2011) DNA structure: alphabet soup for the cellular soul. In: Seligmann H (ed) DNA replication-current advances. InTech, New York

    Google Scholar 

  27. Calladine CR, Drew HR, Luisi BF, Travers AA (1992) Understanding DNA, 3rd edn. Elsevier Academic, Amsterdam

    Google Scholar 

  28. Ghosh A, Bansal M (2003) A glossary of DNA structures from A to Z. Acta Crystallogr Sect D Biol Crystallogr 59:620–626

    Google Scholar 

  29. Strick TR, Allemand J-F, Bensimon D, Bensimon A, Croquette V (1996) The elasticity of a single supercoiled DNA molecule. Science 271:1835–1837

    CAS  Google Scholar 

  30. Lu Y, Weers B, Stellwagen NC (2002) DNA persistence length revisited. Biopolymers 61:261–275

    CAS  Google Scholar 

  31. Chen H, Meisburger SP, Pabit SA, Sutton JL, Webb WW, Pollack L (2012) Ionic strength-dependent persistence lengths of single-stranded RNA and DNA. Proc Natl Acad Sci USA 109:799–804

    CAS  Google Scholar 

  32. Geggier S, Vologodskii A (2010) Sequence dependence of DNA bending rigidity. Proc Natl Acad Sci USA 107:15421–15426

    CAS  Google Scholar 

  33. Geggier S, Kotlyar A, Vologodskii A (2011) Temperature dependence of DNA persistence length. Nucleic Acids Res 39:1419–1426

    CAS  Google Scholar 

  34. Kypr J, Kejnovska I, Renciuk D, Vorlickova M (2009) Circular dichroism and conformational polymorphism of DNA. Nucleic Acids Res 37:1713–1725

    CAS  Google Scholar 

  35. Vorlíčkováa M, Kypra J, Sklenář V (2005) Nucleic acids: spectroscopic methods. In: Worsfold P, Townshend A, Poole C (eds) Encyclopedia of analytical science, 2nd edn. Elsevier, Amsterdam, pp 391–399

    Google Scholar 

  36. Mirkin SM (2001) DNA topology: fundamentals. In: Encyclopedia of life sciences. Wiley, New York, pp 1–11

    Google Scholar 

  37. Alfredsson V (2005) Cryo-TEM studies of DNA and DNA-lipid structures. Curr Opin Colloid Interface Sci 10:269–273

    CAS  Google Scholar 

  38. Lyubchenko YL (2004) DNA structure and dynamics–an atomic force microscopy study. Cell Biochem Biophys 41:75–98

    CAS  Google Scholar 

  39. Fransz P, Hd J (2011) From nucleosome to chromosome: a dynamic organization of genetic information. Plant J 66:4–17

    CAS  Google Scholar 

  40. Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389:251–260

    CAS  Google Scholar 

  41. Travers A (1993) DNA-protein interactions. Chapman and Hall, London

    Google Scholar 

  42. Dobrynina AV, Rubinstein M (2005) Theory of polyelectrolytes in solutions and at surfaces. Prog Polym Sci 30:1049–1118

    Google Scholar 

  43. Radeva T (2001) Physical chemistry of polyelectrolytes. Surfactant science. CRC, Boca Raton

    Google Scholar 

  44. Manning GS (1969) Limiting laws and counterion condensation in polyelectrolyte solutions I. Colligative properties. J Chem Phys 51:924–933

    CAS  Google Scholar 

  45. Rühe J, Ballauff M, Biesalski M, Dziezok P, Gröhn F, Johannsmann D, Houbenov N, Hugenberg N, Konradi R, Minko S, Motornov M, Netz RR, Schmidt M, Seidel C, Stamm M, Stephan T, Usov D, Zhang H (2004) Polyelectrolyte brushes. Adv Polym Sci 165:79–150

    Google Scholar 

  46. Israelachvili J (1985) Intermolecular and surface forces. Academic, London

    Google Scholar 

  47. Thünemann AF, Müller M, Dautzenberg H, Joanny J-F, Löwen H (2004) Polyelectrolyte complexes. Adv Polym Sci 166:19–33

    Google Scholar 

  48. Gohy JF, Varshney SK, Antoun S, Jerome R (2000) Water-soluble complexes formed by sodium poly(4-styrenesulfonate) and a poly(2-vinylpyridinium)-block-poly(ethyleneoxide) copolymer. Macromolecules 33:9298–9305

    CAS  Google Scholar 

  49. Kabanov AV, Bronich TK, Kabanov VA, Yu K, Eisenberg A (1996) Soluble stoichiometric complexes from poly(N-ethyl-4-vinylpyridinium) cations and poly(ethylene oxide)-block-polymethacrylate anions. Macromolecules 29:6797–6802

    CAS  Google Scholar 

  50. Harada A, Kataoka K (1995) Formation of polyion complex micelles in an aqueous milieu from a pair of oppositely-charged block copolymers with poly(ethylene glycol) segments. Macromolecules 28:5294–5299

    CAS  Google Scholar 

  51. Kakizawa Y, Kataoka K (2002) Block copolymer micelles for delivery of gene and related compounds. Adv Drug Deliv Rev 54:203–222

    CAS  Google Scholar 

  52. Voets IK, Keizer AD, Cohen Stuart MA (2009) Complex coacervate core micelles. Adv Colloid Interface Sci 147–148:300–318

    Google Scholar 

  53. Ilarduya CT, Sun Y, Düzgünes N (2010) Gene delivery by lipoplexes and polyplexes. Eur J Pharm Sci 40:159–170

    Google Scholar 

  54. Kabanov AV, Kabanov VA (1998) Interpolyelectrolyte and block ionomer complexes for gene delivery: physicochemical aspects. Adv Drug Deliv Rev 30:49–60

    CAS  Google Scholar 

  55. Davis KA, Matyjaszewski K (2002) Statistical, gradient, block, and graft copolymers by controlled/living radical polymerizations. Adv Polym Sci 159:1–13

    Google Scholar 

  56. Matyjaszewski K (ed) (2003) Advances in controlled/living radical polymerization. ACS symposium series, vol 854. American Chemical Society, Washington

    Google Scholar 

  57. Matyjaszewski K (ed) (2006) Controlled/living radical polymerization: from synthesis to materials. ACS symposium series, vol 944. American Chemical Society, Washington

    Google Scholar 

  58. Xu Y, Plamper F, Ballauff M, Müller AHE (2010) Polyelectrolyte stars and cylindrical brushes. Adv Polym Sci 228:1–38

    CAS  Google Scholar 

  59. Bakeev KN, Izumrudov VA, Kuchanov SI, Zezin AB, Kabanov VA (1992) Kinetics and mechanism of interpolyelectrolyte exchange and addition reactions. Macromolecules 25:4249–4254

    CAS  Google Scholar 

  60. Tang MX, Szoka FC Jr (1998) Structure of polycation-DNA complexes and theory of compaction. In: Kabanov AV, Felgner PL, Seymour LW (eds) Self-assembling complexes for gene delivery. Wiley, New York

    Google Scholar 

  61. Dias RS, Pais AACC, Miguel MG, Lindman B (2003) Modeling of DNA compaction by polycations. J Chem Phys 119:8150–8157

    CAS  Google Scholar 

  62. Sarraguça JMG, Dias RS, Pais AACC (2006) Coil-globule coexistence and compaction of DNA chains. J Biol Phys 32:421–434

    Google Scholar 

  63. Dragan ES, Mihai M, Schwarz S (2006) Polyelectrolyte complex dispersions with a high colloidal stability controlled by the polyion structure and titrant addition rate. Colloid Surf A 290:213–221

    CAS  Google Scholar 

  64. Gärdlund L, Wågberg L, Norgren M (2007) New insights into the structure of polyelectrolyte complexes. J Colloid Interface Sci 312:237–246

    Google Scholar 

  65. Hartig SM, Greene RR, Dikov MM, Prokop A, Davidson JM (2007) Multifunctional nanoparticulate polyelectrolyte complexes. Pharm Res 24:2353–2369

    CAS  Google Scholar 

  66. Philipp B, Dautzenberg H, Linow KJ, Koetz J, Dawydoff W (1989) Polyelectrolyte complexes - recent developments and open problems. Prog Polym Sci 14:91–172

    CAS  Google Scholar 

  67. Giorgetti L, Siggers T, Tiana G, Caprara G, Notarbartolo S, Corona T, Pasparakis M, Milani P, Bulyk ML, Natoli G (2010) Noncooperative interactions between transcription factors and clustered DNA binding sites enable graded transcriptional responses to environmental inputs. Mol Cell 37:418–428

    CAS  Google Scholar 

  68. Danielsen S, Varum KM, Stokke BT (2004) Structural analysis of chitosan mediated DNA condensation by AFM: influence of chitosan molecular parameters. Biomacromolecules 5:928–936

    CAS  Google Scholar 

  69. Bloomfield VA (1996) DNA condensation. Curr Opin Struct Biol 6:334–341

    CAS  Google Scholar 

  70. Ainalem M-L, Carnerup AM, Janiak J, Alfredsson V, Nylander T, Schillen K (2009) Condensing DNA with poly(amido amine) dendrimers of different generations: means of controlling aggregate morphology. Soft Matter 5:2310–2320

    CAS  Google Scholar 

  71. Carnerup AM, Ainalem M-L, Alfredsson V, Nylander T (2011) Condensation of DNA using poly(amido amine) dendrimers: effect of salt concentration on aggregate morphology. Soft Matter 7:760–768

    CAS  Google Scholar 

  72. Kabanov VA, Zezin AB (1984) Soluble interpolymeric complexes as a new class of synthetic polyelectrolytes. Pure Appl Chem 56:343–354

    CAS  Google Scholar 

  73. Kiriy A, Yu J, Stamm M (2006) Interpolyelectrolyte complexes: a single-molecule insight. Langmuir 22:1800–1803

    CAS  Google Scholar 

  74. Dautzenberg H, Rother G (2003) Response of polyelectrolyte complexes to subsequent addition of sodium chloride: time-dependent static light scattering studies. Macromol Chem Phys 205:114–121

    Google Scholar 

  75. Discher DE, Eisenberg A (2002) Polymer vesicles. Science 297(5583):967–973. doi:10.1126/science.1074972

    CAS  Google Scholar 

  76. Lo C-L, Lin S-J, Tsai H-C, Chan W-H, Tsai C-H, Cheng C-HD, Hsiue G-H (2009) Mixed micelle systems formed from critical micelle concentration and temperature-sensitive diblock copolymers for doxorubicin delivery. Biomaterials 30(23–24):3961–3970. doi:10.1016/j.biomaterials.2009.04.002

    CAS  Google Scholar 

  77. Dautzenberg H (1997) Polyelectrolyte complex formation in highly aggregating systems. 1. Effect of salt: polyelectrolyte complex formation in the presence of NaCl. Macromolecules 30:7810–7815

    CAS  Google Scholar 

  78. Michaels AS, Mir L, Schneider NS (1965) A conductometric study of polycation-polyanion reactions in dilute aqueous solution. J Phys Chem 69:1447–1455

    CAS  Google Scholar 

  79. Sukhishvili SA, Kharlampieva E, Izumrudov V (2006) Where polyelectrolyte multilayers and polyelectrolyte complexes meet. Macromolecules 39:8873–8881

    CAS  Google Scholar 

  80. Maskos M, Stauber RH (2011) Characterization of nanoparticles in biological environments. In: Comprehensive biomaterials, vol 3: Methods of analysis. Elsevier, Amsterdam, pp 329–339

    Google Scholar 

  81. Lebovka NI (2012) Aggregation of charged colloidal particles. In: Müller M (ed) Advances in polymer science. Springer, Berlin, doi: 10.1007/12_2012_171

  82. Patchornik A, Berger A, Katchalski E (1957) Poly-L-histidine. J Am Chem Soc 79:5227–5230

    Google Scholar 

  83. Palchaudhuri R, Hergenrother PJ (2007) DNA as a target for anticancer compounds: methods to determine the mode of binding and the mechanism of action. Curr Opin Biotechnol 18:497–503

    CAS  Google Scholar 

  84. Hannon MJ (2007) Supramolecular DNA recognition. Chem Soc Rev 36:280–295

    CAS  Google Scholar 

  85. Mulligan RC (1993) The basic science of gene therapy. Science 260:926–932

    CAS  Google Scholar 

  86. Verma IM, Somia N (1997) Gene therapy – promises, problems and prospects. Nature 389:239–242

    CAS  Google Scholar 

  87. Edelstein ML, Abedi MR, Wixon J, Edelstein RM (2004) Gene therapy clinical trials worldwide 1989–2004 – an overview. J Gene Med 6:597–602

    Google Scholar 

  88. Edelstein ML, Abedi MR, Wixon J (2007) Gene therapy clinical trials worldwide to 2007 – an update. J Gene Med 9:833–842

    Google Scholar 

  89. Palmer DH, Young LS, Mautner V (2006) Cancer gene-therapy: clinical trials. Trends Biotechnol 24:76–82

    CAS  Google Scholar 

  90. Yeung ML, Bennasser Y, Le SY, Jeang KT (2005) siRNA, miRNA and HIV: promises and challenges. Cell Res 15:935–946

    CAS  Google Scholar 

  91. Kay MA, Glorioso JC, Naldini L (2001) Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med 7:33–40

    CAS  Google Scholar 

  92. Behr J-P (1993) Synthetic gene-transfer vectors. Acc Chem Res 26:274–278

    CAS  Google Scholar 

  93. Glover DJ, Lipps HJ, Jans DA (2005) Towards safe, non-viral therapeutic gene expression in humans. Nat Rev 6:299–310

    CAS  Google Scholar 

  94. Kawakami S, Higuchi Y, Hashida M (2008) Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide. J Pharm Sci 97:726–745

    CAS  Google Scholar 

  95. Scholz C, Wagner E (2012) Therapeutic plasmid DNA versus siRNA delivery: Common and different tasks for synthetic carriers. J Control Release 161:554–565

    CAS  Google Scholar 

  96. Zamore PD, Tuschl T, Sharp PA, Bartel DP (2000) RNAi. Cell Res 101:25–33

    CAS  Google Scholar 

  97. Bonetta L (2004) RNAi: silencing never sounded better. Nat Methods 1:79–86

    CAS  Google Scholar 

  98. Pecot CV, Calin GA, Coleman RL, Lopez-Berestein G, Sood AK (2011) RNA interference in the clinic: challenges and future directions. Nat Rev Cancer 11:59–67

    CAS  Google Scholar 

  99. Wilson RW, Bloomfield VA (1979) Counterion-induced condensation of deoxyribonucleic acid. A light-scattering study. Biochemistry 18:2192–2196

    CAS  Google Scholar 

  100. Agarwal S, Zhang Y, Maji S, Greiner A (2012) PDMAEMA based gene delivery materials. Mater Today 15:388–393

    CAS  Google Scholar 

  101. Brissault B, Kichler A, Guis C, Leborgne C, Danos O, Cheradame H (2003) Synthesis of linear polyethylenimine derivatives for DNA transfection. Bioconjug Chem 14:581–587

    CAS  Google Scholar 

  102. Rungsardthong U, Ehtezazi T, Bailey L, Armes SP, Garnett MC, Stolnik S (2003) Effect of polymer ionization on the interaction with DNA in nonviral gene delivery systems. Biomacromolecules 4:683–690

    CAS  Google Scholar 

  103. Nimesh S, Aggarwal A, Kumar P, Singh Y, Gupta KC, Chandra R (2007) Influence of acyl chain length on transfection mediated by acylated PEI nanoparticles. Int J Pharm 337:265–274

    CAS  Google Scholar 

  104. Gabrielson NP, Pack DW (2006) Acetylation of polyethylenimine enhances gene delivery via weakened polymer/DNA interactions. Biomacromolecules 7:2427–2435

    CAS  Google Scholar 

  105. Tang GP, Zeng JM, Gao SJ, Ma YX, Shi L, Li Y, Too H-P, Wang S (2003) Polyethylene glycol modified polyethylenimine for improved CNS gene transfer: effects of PEGylation extent. Biomaterials 24:2351–2362

    CAS  Google Scholar 

  106. Brumbach JH, Lin C, Yockman J, Kim WJ, Blevins KS, Engbersen JFJ, Feijen J, Kim SW (2010) Mixtures of poly(triethylenetetramine/cystamine bisacrylamide) and poly(triethylenetetramine/cystamine bisacrylamide)-g-poly(ethylene glycol) for improved gene delivery. Bioconjug Chem 21:1753–1761

    CAS  Google Scholar 

  107. Allen MHJ, Green MD, Getaneh HK, Miller KM, Long TE (2011) Tailoring charge density and hydrogen bonding of imidazolium copolymers for efficient gene delivery. Biomacromolecules 12:2243–2250

    CAS  Google Scholar 

  108. Prevette LE, Kodger TE, Reineke TM, Lynch ML (2007) Deciphering the role of hydrogen bonding in enhancing pDNA-polycation interactions. Langmuir 23:9773–9784

    CAS  Google Scholar 

  109. Georgiou TK, Vamvakaki M, Patrickios CS (2004) Nanoscopic cationic methacrylate star homopolymers: synthesis by group transfer polymerization, characterization and evaluation as transfection reagents. Biomacromolecules 5:2221–2229

    CAS  Google Scholar 

  110. Deshpande MC, Garnett MC, Vamvakaki M, Bailey L, Armes SP, Stolnik S (2002) Influence of polymer architecture on the structure of complexes formed by PEG-tertiary amine methacrylate copolymers and phosphorothioate oligonucleotide. J Control Release 81:185–199

    CAS  Google Scholar 

  111. Luten J, van Nostrum CF, Smedt SCD, Hennink WE (2008) Biodegradable polymers as non-viral carriers for plasmid DNA delivery. J Control Release 126:97–110

    CAS  Google Scholar 

  112. Laga R, Carlisle R, Tangney M, Ulbrich K, Seymour LW (2012) Polymer coatings for delivery of nucleic acid therapeutics. J Control Release 161:537–553

    CAS  Google Scholar 

  113. Chan P, Kurisawa M, Chung JE, Yang Y-Y (2007) Synthesis and characterization of chitosan-g-poly(ethylene glycol)-folate as a non-viral carrier for tumor-targeted gene delivery. Biomaterials 28:540–549

    CAS  Google Scholar 

  114. Blessing T, Kursa M, Holzhauser R, Kircheis R, Wagner E (2001) Different strategies for formation of PEGylated EGF-conjugated PEI/DNA complexes for targeted gene delivery. Bioconjug Chem 12:529–537

    CAS  Google Scholar 

  115. Kursa M, Walker GF, Roessler V, Ogris M, Roedl W, Kircheis R, Wagner E (2003) Novel shielded transferrin-polyethylene glycol-polyethylenimine/DNA complexes for systemic tumor-targeted gene transfer. Bioconjug Chem 14:222–231

    CAS  Google Scholar 

  116. Nishikawa M, Huang L (2001) Non viral vectors in the new millennium: delivery barriers in gene transfer. Hum Gene Ther 12:861–870

    CAS  Google Scholar 

  117. Grigsby CL, Leong KW (2010) Balancing protection and release of DNA: tools to address a bottleneck of non-viral gene delivery. J R Soc Interface 7:S67–S82

    CAS  Google Scholar 

  118. Soliman M, Allen S, Davies MC, Alexander C (2010) Responsive polyelectrolyte complexes for triggered release of nucleic acid therapeutics. Chem Commun 46:5421–5433

    CAS  Google Scholar 

  119. Spain SG, Yasayan G, Soliman M, Heath F, Saeed AO, Alexander C (2011) Nanoparticles for nucleic acid delivery. In: Ducheyne P (ed) Comprehensive biomaterials, vol 4. Elsevier, Amsterdam, pp 389–410

    Google Scholar 

  120. Sonawane ND, Szoka FC Jr, Verkman A (2003) Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine DNA polyplexes. J Biol Chem 278:44826–44831

    CAS  Google Scholar 

  121. Hunter AC, Moghimi SM (2010) Cationic carriers of genetic material and cell death: a mitochondrial tale. Biochim Biophys Acta 1797:1203–1209

    CAS  Google Scholar 

  122. Izumrudov VA, Zhiryakova MV (1999) Stability of DNA-containing interpolyelectrolyte complexes in water-salt solutions. Macromol Chem Phys 200:2533–2540

    CAS  Google Scholar 

  123. Xu FJ, Chai MY, Li WB, Ping Y, Tang GP, Yang WT, Ma J, Liu FS (2010) Well-defined poly(2-hydroxyl-3-(2-hydroxyethylamino)propyl methacrylate) vectors with low toxicity and high gene transfection efficiency. Biomacromolecules 11:1437–1442

    CAS  Google Scholar 

  124. Ma M, Li F, Yuan Z-F, Zhuo R-X (2010) Influence of hydroxyl groups on the biological properties of cationic polymethacrylates as gene vectors. Acta Biomater 6:2658–2665

    CAS  Google Scholar 

  125. Hemp ST, Allen J, Green MD, Long TE (2012) Phosphonium-containing polyelectrolytes for nonviral gene delivery. Biomacromolecules 13:231–238

    CAS  Google Scholar 

  126. Zelikin AN, Putnam D, Shastri P, Langer R, Izumrudov VA (2002) Aliphatic ionenes as gene delivery agents: elucidation of structure-function relationship through modification of charge density and polymer length. Bioconjug Chem 13:548–553

    CAS  Google Scholar 

  127. Izumrudov VA, Wahlund P-O, Gustavsson P-E, Larsson P-O, Galaev IY (2003) Factors controlling phase separation in water-salt solutions of DNA and polycations. Langmuir 19:4733–4739

    CAS  Google Scholar 

  128. Andersson T, Aseyev V, Tenhu H (2004) Complexation of DNA with poly(methacryl oxyethyl trimethylammonium chloride) and its poly(oxyethylene) grafted analogue. Biomacromolecules 5:1853–1861

    CAS  Google Scholar 

  129. Nisha CK, Manorama SV, Ganguli M, Maiti S, Kizhakkedathu JN (2004) Complexes of poly(ethylene glycol)-based cationic random copolymer and calf thymus DNA: a complete biophysical characterization. Langmuir 20:2386–2396

    CAS  Google Scholar 

  130. Howard KA, Dash PR, Read ML, Ward K, Tomkins LM, Nazarova O, Ulbrich K, Seymour LW (2000) Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA. Biochim Biophys Acta 1475:245–255

    CAS  Google Scholar 

  131. Kimura T, Yamaoka T, Iwase R, Murakami A (2002) Effect of physicochemical properties of polyplexes composed of chemically modified PL derivatives on transfection efficiency in vitro. Macromol Biosci 2:437–446

    CAS  Google Scholar 

  132. Licciardi M, Campisi M, Cavallaro G, Carlisi B, Giammona G (2006) Novel cationic polyaspartamide with covalently linked carboxypropyl-trimethyl ammonium chloride as a candidate vector for gene delivery. Eur Polym J 42:823–834

    CAS  Google Scholar 

  133. Caputo A, Betti M, Altavilla G, Bonaccorsi A, Boarini C, Marchisio M, Buttò S, Sparnacci K, Laus M, Tondelli L, Ensoli B (2002) Micellar-type complexes of tailor-made synthetic block copolymers containing the HIV-1 tat DNA for vaccine application. Vaccine 20:2303–2317

    CAS  Google Scholar 

  134. Itaka K, Ishii T, Hasegawa Y, Kataoka K (2010) Biodegradable polyamino acid-based polycations as safe and effective gene carrier minimizing cumulative toxicity. Biomaterials 31:3707–3714

    CAS  Google Scholar 

  135. Zhang M, Liu M, Xue Y-N, Huang S-W, Zhuo R-X (2009) Polyaspartamide-based oligo-ethylenimine brushes with high buffer capacity and low cytotoxicity for highly efficient gene delivery. Bioconjug Chem 20:440–446

    CAS  Google Scholar 

  136. Cavallaro G, Scirè S, Licciardi M, Ogris M, Wagner E, Giammona G (2008) Polyhydroxyethylaspartamide-spermine copolymers: efficient vectors for gene delivery. J Control Release 131:54–63

    CAS  Google Scholar 

  137. Liu M, Chen J, Cheng Y-P, Xue Y-N, Zhuo R-X, Huang S-W (2010) Novel poly(amidoamine)s with pendant primary amines as highly efficient gene delivery vectors. Macromol Biosci 10:384–392

    CAS  Google Scholar 

  138. Kim T-I, Kim SW (2011) Bioreducible polymers for gene delivery. React Funct Polym 71:344–349

    CAS  Google Scholar 

  139. Lin C, Blaauboer C-J, Timoneda MM, Lok MC, van Steenbergen M, Hennink WE, Zhong Z, Feijen J, Engbersen JFJ (2008) Bioreducible poly(amido amine)s with oligoamine side chains: synthesis, characterization, and structural effects on gene delivery. J Control Release 126:166–174

    CAS  Google Scholar 

  140. Du F-S, Wang Y, Zhang R, Li Z-C (2010) Intelligent nucleic acid delivery systems based on stimuli-responsive polymers. Soft Matter 6:835–848

    CAS  Google Scholar 

  141. Verbaan FJ, Crommelin DJA, Hennink WE, Storm G (2005) Poly(2-(dimethylamino)ethyl methacrylate)-based polymers for the delivery of genes in vitro and in vivo. In: Amiji MM (ed) Polymeric gene delivery-principles and applications. CRC, Boca Raton

    Google Scholar 

  142. van de Wetering P, Cherng J-Y, Talsma H, Crommelin DJA, Hennink WE (1998) 2-(dimethylamino)ethyl methacrylate based (co)polymers as gene transfer agents. J Control Release 53:145–153

    Google Scholar 

  143. van de Wetering P, Moret EE, Schuurmans-Nieuwenbroek NME, van Steenbergen MJ, Hennink WE (1999) Structure-activity relationships of water-soluble cationic methacrylate/methacrylamide polymers for nonviral gene delivery. Bioconjug Chem 10:589–597

    Google Scholar 

  144. Asayama S, Maruyama A, Cho C-S, Akaike T (1997) Design of comb-type polyamine copolymers for a novel pH-sensitive DNA carrier. Bioconjug Chem 8:833–838

    CAS  Google Scholar 

  145. Jiang X, Lok MC, Hennink WE (2007) Degradable-brushed pHEMA-pDMAEMA synthesized via ATRP and click chemistry for gene delivery. Bioconjug Chem 18:2077–2084

    CAS  Google Scholar 

  146. Dubruel P, Strycker JD, Westbroek P, Bracke K, Temmerman E, Vandervoort J, Ludwig A, Schacht E (2002) Synthetic polyamines as vectors for gene delivery. Polym Int 51:948–957

    CAS  Google Scholar 

  147. Hinrichs WLJ, Schuurmans-Nieuwenbroek NME, van de Wetering P, Hennink WE (1999) Thermosensitive polymers as carriers for DNA delivery. J Control Release 60:249–259

    CAS  Google Scholar 

  148. Oupicky D, Reschel T, Konak C, Oupicka L (2003) Temperature-controlled behavior of self-assembly gene delivery vectors based on complexes of DNA with poly(L-lysine)-graft-poly(N-isopropylacrylamide). Macromolecules 36:6863–6872

    CAS  Google Scholar 

  149. Cheng N, Liu W, Cao Z, Ji W, Liang D, Guo G, Zhang J (2006) A study of thermoresponsive poly(N-isopropylacrylamide)/polyarginine bioconjugate non-viral transgene vectors. Biomaterials 27:4984–4992

    CAS  Google Scholar 

  150. Putnam D, Gentry CA, Pack DW, Langer R (2001) Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini. Proc Natl Acad Sci USA 98:1200–1205

    CAS  Google Scholar 

  151. Chen DJ, Majors BS, Zelikin A, Putnam D (2005) Structure-function relationships of gene delivery vectors in a limited polycation library. J Control Release 103:273–283

    CAS  Google Scholar 

  152. Burckhardt G, Zimmer C, Luck G (1976) Conformation and reactivity of DNA in the complex with protein: IV. Circular dichroism of poly-l-histidine model complexes with DNA polymers and specificity of the interaction. Nucleic Acids Res 3:561–580

    CAS  Google Scholar 

  153. Benns JM, Choi J-S, Mahato RI, Park J-S, Kim SW (2000) pH-sensitive cationic polymer gene delivery vehicle: N-Ac-poly(L-histidine)-graft-poly(L-lysine) comb shaped polymer. Bioconjug Chem 11:637–645

    CAS  Google Scholar 

  154. Roufai MB, Midoux P (2001) 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. Bioconjug Chem 12:92–99

    Google Scholar 

  155. Kim TH, Ihm JE, Choi YJ, Nah JW, Cho CS (2003) Efficient gene delivery by urocanic acid-modified chitosan. J Control Release 93:389–402

    CAS  Google Scholar 

  156. Park JS, Han TH, Lee KY, Han SS, Hwang JJ, Moon D, Kim SY, Cho YW (2006) N-acetyl histidine-conjugated glycol chitosan self-assembled nanoparticles for intracytoplasmic delivery of drugs: endocytosis, exocytosis and drug release. J Control Release 115:37–45

    CAS  Google Scholar 

  157. Mishra S, Heidel JD, Webster P, Davis ME (2006) Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processes. J Control Release 116:179–191

    CAS  Google Scholar 

  158. Swami A, Aggarwal A, Pathak A, Patnaik S, Kumar P, Singh Y, Gupta KC (2007) Imidazolyl-PEI modified nanoparticles for enhanced gene delivery. Int J Pharm 335:180–192

    CAS  Google Scholar 

  159. Pichon C, Goncalves C, Midoux P (2001) Histidine-rich peptides and polymers for nucleic acids delivery. Adv Drug Deliv Rev 53:75–94

    CAS  Google Scholar 

  160. Midoux P, Pichon C, Yaouanc J-J, Jaffrès P-A (2009) Chemical vectors for gene delivery: a current review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers. Br J Pharmacol 157:166–178

    CAS  Google Scholar 

  161. Dekie L, Toncheva V, Dubruel P, Schacht EH, Barrett L, Seymour LW (2000) Poly-L-glutamic acid derivatives as vectors for gene therapy. J Control Release 65:187–202

    CAS  Google Scholar 

  162. Dubruel P, Dekie L, Schacht E (2003) Poly-L-glutamic acid derivatives as multifunctional vectors for gene delivery. Part A. Synthesis and physicochemical evaluation. Biomacromolecules 4:1168–1176

    CAS  Google Scholar 

  163. Dubruel P, Dekie L, Christiaens B, Vanloo B, Rosseneu M, Vandekerckhove J, Mannisto M, Urtti A, Schacht E (2003) Poly-L-glutamic acid derivatives as multifunctional vectors for gene delivery. Part B. Biological evaluation. Biomacromolecules 4:1177–1183

    CAS  Google Scholar 

  164. Pack DW, Putnam D, Langer R (2000) Design of imidazole-containing endosomolytic biopolymers for gene delivery. Biotechnol Bioeng 67:217–223

    CAS  Google Scholar 

  165. Ramsay E, Hadgraft J, Birchall J, Gumbleton M (2000) Examination of the biophysical interaction between plasmid DNA and the polycations, polylysine and polyornithine, as a basis for their differential gene transfection in-vitro. Int J Pharm 210:97–107

    CAS  Google Scholar 

  166. Blauer G, Alfassi ZB (1967) A comparison between poly-α, L-ornithine and poly-α, L-lysine in solution: the effect of a CH2 group on the side-chain on the conformation of the poly-α-amino acids. Biochim Biophys Acta 133:206–218

    CAS  Google Scholar 

  167. Morgan DML, Larvin VL, Pearson JD (1989) Biochemical characterisation of polycation-induced cytotoxity to human vascular endothelial cells. J Cell Sci 94:553–559

    CAS  Google Scholar 

  168. Reich Z, Ittah Y, Weinberger S, Minsky A (1990) Chiral and structural discrimination in binding of polypeptides with condensed nucleic acid structures. J Biol Chem 265:5590–5594

    CAS  Google Scholar 

  169. Mann A, Khan MA, Shukla V, Ganguli M (2007) Atomic force microscopy reveals the assembly of potential DNA “nanocarriers” by poly-L-ornithine. Biophys Chem 129:126–136

    CAS  Google Scholar 

  170. Lim Y-B, Kim C-H, Kim K, Kim SW, Park J-S (2000) Development of a safe gene delivery system using biodegradable polymer, poly[α-(4-aminobutyl)-L-glycolic acid]. J Am Chem Soc 122:6524–6525

    CAS  Google Scholar 

  171. Putnam D, Langer R (1999) Poly(4-hydroxy-L-proline ester): low-temperature polycondensation and plasmid DNA complexation. Macromolecules 32:3658–3662

    CAS  Google Scholar 

  172. Simon RJ, Kania RS, Zuckermann RN, Huebner VD, Jewell DA, Banville S, Ng S, Wang L, Rosenberg S, Marlowe CK, Spellmeyer DC, Tan R, Frankel AD, Santi DV, Cohen FE, Bartlett PA (1992) Peptoids: a modular approach to drug discovery. Proc Natl Acad Sci USA 89:9367–9371

    CAS  Google Scholar 

  173. Fowler SA, Blackwell HE (2009) Structure-function relationships in peptoids: recent advances toward deciphering the structural requirements for biological function. Org Biomol Chem 7:1508–1524

    CAS  Google Scholar 

  174. Zuckermann RN, Kodadek T (2009) Peptoids as potential therapeutics. Curr Opin Mol Ther 11:299–307

    CAS  Google Scholar 

  175. Murphy JE, Uno T, Hamer JD, Cohen FE, Dwarki V, Zuckermann RN (1998) A combinatorial approach to the discovery of efficient cationic peptoid reagents for gene delivery. Proc Natl Acad Sci USA 95:1517–1522

    CAS  Google Scholar 

  176. Lobo BA, Vetro JA, Suich DM, Zuckermann RN, Middaugh CR (2003) Structure/function analysis of peptoid/lipitoid: DNA complexes. J Pharm Sci 92:1905–1918

    CAS  Google Scholar 

  177. Ji W, Panus D, Palumbo RN, Tang R, Wang C (2011) Poly(2-aminoethyl methacrylate) with well-defined chain length for DNA vaccine delivery to dendritic cells. Biomacromolecules 12:4373–4385

    CAS  Google Scholar 

  178. Luo S, Cheng R, Meng F, Park TG, Zhong Z (2011) Water soluble poly(histamine acrylamide) with superior buffer capacity mediates efficient and nontoxic in vitro gene transfection. J Polym Sci A Polym Chem 49:3366–3373

    CAS  Google Scholar 

  179. Sun H, Gao C (2010) Facile synthesis of multiamino vinyl poly(amino acid)s for promising bioapplications. Biomacromolecules 11:3609–3616

    CAS  Google Scholar 

  180. Wolfert MA, Dash PR, Nazarova O, Oupicky D, Seymour LW, Smart S, Strohalm J, Ulbrich K (1999) Polyelectrolyte vectors for gene delivery: influence of cationic polymer on biophysical properties of complexes formed with DNA. Bioconjug Chem 10:993–1004

    CAS  Google Scholar 

  181. Venkataraman S, Ong WL, Ong ZY, Loo SCJ, Ee PLR, Yang YY (2011) The role of PEG architecture and molecular weight in the gene transfection performance of PEGylated poly(dimethylaminoethyl methacrylate) based cationic polymers. Biomaterials 32:2369–2378

    CAS  Google Scholar 

  182. Rungsardthong U, Deshpande M, Bailey L, Vamvakaki M, Armes SP, Garnett MC, Stolnik S (2001) Copolymers of amine methacrylate with poly(ethylene glycol) as vectors for gene therapy. J Control Release 73:359–380

    CAS  Google Scholar 

  183. Stolnik S, Illum L, Davis SS (1995) Long circulating microparticulate drug carriers. Adv Drug Deliv Rev 16:195–214

    CAS  Google Scholar 

  184. Kleideiter G, Nordmeier E (1999) Poly(ethylene glycol)-induced DNA condensation in aqueous/methanol containing low-molecular-weight electrolyte solutions. Part II. Comparison between experiment and theory. Polymer 40:4025–4033

    CAS  Google Scholar 

  185. Toncheva V, Wolfert MA, Dash PR, Oupicky D, Ulbrich K, Seymour LW, Schacht EH (1998) Novel vectors for gene delivery formed by self-assembly of DNA with poly(L-lysine) grafted with hydrophilic polymers. Biochim Biophys Acta 1380:354–368

    CAS  Google Scholar 

  186. Deshpande MC, Davies MC, Garnett MC, Williams PM, Armitage D, Bailey L, Vamvakaki M, Armes SP, Stolnik S (2004) The effect of poly(ethylene glycol) molecular architecture on cellular interaction and uptake of DNA complexes. J Control Release 97:143–156

    CAS  Google Scholar 

  187. Ziebarth J, Wang Y (2010) Coarse-grained molecular dynamics simulations of DNA condensation by block copolymer and formation of core-corona structures. J Phys Chem B 114:6225–6232

    CAS  Google Scholar 

  188. Petersen H, Fechner PM, Martin AL, Kunath K, Stolnik S, Roberts CJ, Fischer D, Davies MC, Kissel T (2002) Polyethylenimine-graft-poly(ethylene glycol) copolymers: influence of copolymer block structure on DNA complexation and biological activities as gene delivery system. Bioconjug Chem 13:845–854

    CAS  Google Scholar 

  189. Wakebayashi D, Nishiyama N, Itaka K, Miyata K, Yamasaki Y, Harada A, Koyama H, Nagasaki Y, Kataoka K, Harada A (2004) Polyion complex micelles of pDNA with acetal-poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) block copolymer as the gene carrier system: physicochemical properties of micelles relevant to gene transfection efficacy. Biomacromolecules 5:2128–2136

    CAS  Google Scholar 

  190. Itaka K, Yamauchi K, Harada A, Nakamura K, Kawaguchi H, Kataoka K (2003) Polyion complex micelles from plasmid DNA and poly(ethylene glycol)-poly(l-lysine) block copolymer as serum-tolerable polyplex system: physicochemical properties of micelles relevant to gene transfection efficiency. Biomaterials 24:4495–4506

    CAS  Google Scholar 

  191. Tan JF, Too HP, Hatton TA, Tam KC (2006) Aggregation behavior and thermodynamics of binding between poly(ethylene oxide)-block-poly(2-(diethylamino)ethyl methacrylate) and plasmid DNA. Langmuir 22:3744–3750

    CAS  Google Scholar 

  192. Wang C, Tam KC (2002) New insights on the interaction mechanism within oppositely charged polymer/surfactant systems. Langmuir 18:6484–6490

    CAS  Google Scholar 

  193. Uzgun S, Akdemir O, Hasenpusch G, Maucksch C, Golas MM, Sander B, Stark H, Imker R, Lutz J-F, Rudolph C (2010) Characterization of tailor-made copolymers of oligo(ethylene glycol) methyl ether methacrylate and N, N-dimethylaminoethyl methacrylate as nonviral gene transfer agents: influence of macromolecular structure on gene vector particle properties and transfection efficiency. Biomacromolecules 11:39–50

    CAS  Google Scholar 

  194. Verbaan FJ, Oussoren C, Snel CJ, Crommelin DJA, Hennink WE, Storm G (2004) Steric stabilization of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes mediates prolonged circulation and tumor targeting in mice. J Gene Med 6:64–75

    CAS  Google Scholar 

  195. Yao Y, Feng D-F, Wu Y-P, Ye Q-J, Liu L, Li X-X, Hou S, Yang Y-L, Wang C, Li L, Feng X-Z (2011) Influence of block sequences in polymer vectors for gene transfection in vitro and toxicity assessment of zebrafish embryos in vivo. J Mater Chem 21:4538–4545

    CAS  Google Scholar 

  196. Xu F-J, Li H, Li J, Zhang Z, Kang E-T, Neoh K-G (2008) Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino) ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery. Biomaterials 29:3023–3033

    CAS  Google Scholar 

  197. Brissault B, Kichler A, Leborgne C, Danos O, Cheradame H, Gau J, Auvray L, Guis C (2006) Synthesis, characterization, and gene transfer application of poly(ethylene glycol-b-ethylenimine) with high molar mass polyamine block. Biomacromolecules 7:2863–2870

    CAS  Google Scholar 

  198. Liu X-Q, Du J-Z, Zhang C-P, Zhao F, Yang X-Z, Wang J (2010) Brush-shaped polycation with poly(ethylenimine)-b-poly(ethylene glycol) side chains as highly efficient gene delivery vector. Int J Pharm 392:118–126

    CAS  Google Scholar 

  199. Yang J, Zhang P, Tang L, Sun P, Liu W, Sun P, Zuo A, Liang D (2010) Temperature-tuned DNA condensation and gene transfection by PEI-g-(PMEO2MA-b-PHEMA) copolymer-based nonviral vectors. Biomaterials 31:144–155

    Google Scholar 

  200. Tv E, Zwicker S, Pidhatika B, Konradi R, Textor M, Hall H, Lühmann T (2011) Formation and characterization of DNA-polymer-condensates based on poly(2-methyl-2-oxazoline) grafted poly(L-lysine) for non-viral delivery of therapeutic DNA. Biomaterials 32:5291–5303

    Google Scholar 

  201. Bikram M, Ahn C-H, Chae SY, Lee M, Yockman JW, Kim SW (2004) Biodegradable poly(ethylene glycol)-co-poly(L-lysine)-g-histidine multiblock copolymers for nonviral gene delivery. Macromolecules 37:1903–1916

    CAS  Google Scholar 

  202. Putnam D, Zelikin AN, Izumrudov VA, Langer R (2003) Polyhistidine-PEG: DNA nanocomposites for gene delivery. Biomaterials 24:4425–4433

    CAS  Google Scholar 

  203. Kanayama N, Fukushima S, Nishiyama N, Itaka K, Jang W-D, Miyata K, Yamasaki Y, Chung U-I, Kataoka K (2006) A PEG-based biocompatible block catiomer with high buffering capacity for the construction of polyplex micelles showing efficient gene transfer toward primary cells. ChemMedChem 1:439–444

    CAS  Google Scholar 

  204. Miyata K, Fukushima S, Nishiyama N, Yamasaki Y, Kataoka K (2007) PEG-based block catiomers possessing DNA anchoring and endosomal escaping functions to form polyplex micelles with improved stability and high transfection efficacy. J Control Release 122:252–260

    CAS  Google Scholar 

  205. Vuillaume PY, Brunelle M, Calsteren M-RV, Laurent-Lewandowski S, Begin A, Lewandowski R, Talbot BG, ElAzhary Y (2005) Synthesis and characterization of new permanently charged poly(amidoammonium) salts and evaluation of their DNA complexes for gene transport. Biomacromolecules 6:1769–1781

    CAS  Google Scholar 

  206. Thomas M, Klibanov AM (2002) Enhancing polyethylenimine’s delivery of plasmid DNA into mammalian cells. Proc Natl Acad Sci USA 99:14640–14645

    CAS  Google Scholar 

  207. Kabanov AV, Astafyeva IV, Chikindas ML, Rosenblat CF, Kiselev VI, Severin ES, Kabanov VA (1991) DNA interpolyelectrolyte complexes as a tool for efficient cell transformation. Biopolymers 31:1437–1443

    CAS  Google Scholar 

  208. Doody AM, Korley JN, Dang KP, Zawaneh PN, Putnam D (2006) Characterizing the structure/function parameter space of hydrocarbon-conjugated branched polyethylenimine for DNA delivery in vitro. J Control Release 116:227–237

    CAS  Google Scholar 

  209. Liu Z, Zhang Z, Zhou C, Jiao Y (2010) Hydrophobic modifications of cationic polymers for gene delivery. Prog Polym Sci 35:1144–1162

    CAS  Google Scholar 

  210. Juan AS, Letourneur D, Izumrudov VA (2007) Quaternized poly(4-vinylpyridine)s as model gene delivery polycations: structure-function study by modification of side chain hydrophobicity and degree of alkylation. Bioconjug Chem 18:922–928

    Google Scholar 

  211. Vuillaume PY, Brunelle M, Bazuin CG, Talbot BG, Begin A, Calsteren M-RV, Laurent-Lewandowski S (2009) Tail-end amphiphilic dimethylaminopyridinium-containing polymethacrylates for gene delivery. New J Chem 33:1941–1950

    CAS  Google Scholar 

  212. Asayama S, Hakamatani T, Kawakami H (2010) Synthesis and characterization of alkylated poly(1-vinylimidazole) to control the stability of its DNA polyion complexes for gene delivery. Bioconjug Chem 21:646–652

    CAS  Google Scholar 

  213. Filippov SK, Konak C, Kopeckov P, Starovoytova L, Spirkova M, Stepanek P (2010) Effect of hydrophobic interactions on properties and stability of DNA-Polyelectrolyte complexes. Langmuir 26:4999–5006

    CAS  Google Scholar 

  214. Kabanov AV, Kabanov VA (1995) DNA complexes with polycations for the delivery of genetic material into cells. Bioconjug Chem 6:7–20

    CAS  Google Scholar 

  215. Oupicky D, Konak C, Ulbrich K, Wolfert MA, Seymour LW (2000) DNA delivery systems based on complexes of DNA with synthetic polycations and their copolymers. J Control Release 65:149–171

    CAS  Google Scholar 

  216. Sun X, Liu C, Liu D, Li P, Zhang N (2012) Novel biomimetic vectors with endosomal-escape agent enhancing gene transfection efficiency. Int J Pharm 425:62–72

    CAS  Google Scholar 

  217. Wakefield DH, Klein JJ, Wolff JA, Rozema DB (2005) Membrane activity and transfection ability of amphipathic polycations as a function of alkyl group size. Bioconjug Chem 16:1204–1208

    CAS  Google Scholar 

  218. Wang C-H, Hsiue G-H (2005) Polymer-DNA hybrid nanoparticles based on folate-polyethylenimine-block-poly(L-lactide). Bioconjug Chem 16:391–396

    CAS  Google Scholar 

  219. Bromberg L, Deshmukh S, Temchenko M, Iourtchenko L, Alakhov V, Alvarez-Lorenzo C, Barreiro-Iglesias R, Concheiro A, Hatton TA (2005) Polycationic block copolymers of poly(ethylene oxide) and poly(propylene oxide) for cell transfection. Bioconjug Chem 16:626–633

    CAS  Google Scholar 

  220. Alvarez-Lorenzo C, Barreiro-Iglesias R, Concheiro A (2005) Biophysical characterization of complexation of DNA with block copolymers of poly(2-dimethylaminoethyl) methacrylate, poly(ethylene oxide), and poly(propylene oxide). Langmuir 21:5142–5148

    CAS  Google Scholar 

  221. Lidgi-Guigui N, Guis C, Brissault B, Kichler A, Leborgne C, Scherman D, Labdi S, Curmi PA (2010) Investigation of DNA condensing properties of amphiphilic triblock cationic polymers by atomic force microscopy. Langmuir 26:17552–17557

    CAS  Google Scholar 

  222. Wang Y, Gao S, Ye W-H, Yoon HS, Yang Y-Y (2006) Co-delivery of drugs and DNA from cationic core-shell nanoparticles self-assembled from a biodegradable copolymer. Nat Mater 5:791–796

    CAS  Google Scholar 

  223. Guo S, Qiao Y, Wang W, He H, Deng L, Xing J, Xu J, Liang X-J, Dong A (2010) Poly(ε-caprolactone)-graft-poly(2-(N, N-dimethylamino) ethyl methacrylate) nanoparticles: pH dependent thermo-sensitive multifunctional carriers for gene and drug delivery. J Mater Chem 20:6935–6941

    CAS  Google Scholar 

  224. Li Y-Y, Hua S-H, Xiao W, Wang H-Y, Luo X-H, Li C, Cheng S-X, Zhang X-Z, Zhuo R-X (2011) Dual-vectors of anti-cancer drugs and genes based on pH-sensitive micelles self-assembled from hybrid polypeptide copolymers. J Mater Chem 21:3100–3106

    CAS  Google Scholar 

  225. Izumrudov VA, Zelikin AN, Zhiryakova MV, Jaeger W, Bohrisch J (2003) Interpolyelectrolyte reactions in solutions of polycarboxybetaines. J Phys Chem B 107:7982–7986

    CAS  Google Scholar 

  226. Izumrudov VA, Domashenko NI, Zhiryakova MV, Davydova OV (2005) Interpolyelectrolyte reactions in solutions of polycarboxybetaines, 2: Influence of alkyl spacer in the betaine moieties on complexing with polyanions. J Phys Chem B 109:17391–17399

    CAS  Google Scholar 

  227. Ishihara K, Nomura H, Mihara T, Kurita K, Iwasaki Y, Nakabayashi N (1998) Why do phospholipid polymers reduce protein adsorption? J Biomed Mater Res A 39:323–330

    CAS  Google Scholar 

  228. Konno T, Kurita K, Iwasaki Y, Nakabayashi N, Ishihara K (2001) Preparation of nanoparticles composed with bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer. Biomaterials 22:1883–1889

    CAS  Google Scholar 

  229. Lam JKW, Ma Y, Armes SP, Lewis AL, Baldwin T, Stolnik S (2004) Phosphorylcholine-polycation diblock copolymers as synthetic vectors for gene delivery. J Control Release 100:293–312

    CAS  Google Scholar 

  230. Chim YTA, Lam JKW, Ma Y, Armes SP, Lewis AL, Roberts CJ, Stolnik S, Tendler SJB, Davies MC (2005) Structural study of DNA condensation induced by novel phosphorylcholine-based copolymers for gene delivery and relevance to DNA protection. Langmuir 21:3591–3598

    CAS  Google Scholar 

  231. Ahmed M, Bhuchar N, Ishihara K, Narain R (2011) Well-controlled cationic water-soluble phospholipid polymer-DNA nanocomplexes for gene delivery. Bioconjug Chem 22:1228–1238

    CAS  Google Scholar 

  232. Dai F, Wang P, Wang Y, Tang L, Yang J, Liu W, Li H, Wang G (2008) Double thermoresponsive polybetaine-based ABA triblock copolymers with capability to condense DNA. Polymer 49:5322–5328

    CAS  Google Scholar 

  233. Wang J, Zhang P-C, Lu H-F, Ma N, Wang S, Mao H-Q, Leong KW (2002) New polyphosphoramidate with a spermidine side chain as a gene carrier. J Control Release 83:157–168

    CAS  Google Scholar 

  234. Ren Y, Jiang X, Pan D, Mao H-Q (2010) Charge density and molecular weight of polyphosphoramidate gene carrier: are key parameters influencing its DNA compaction ability and transfection efficiency. Biomacromolecules 11:3432–3439

    CAS  Google Scholar 

  235. Khan M, Beniah G, Wiradharma N, Guo XD, Yang YY (2010) Brush-like amphoteric poly[isobutylene-alt-(maleic acid)-graft-oligoethyleneamine)]/DNA complexes for efficient gene transfection. Macromol Rapid Commun 31:1142–1147

    CAS  Google Scholar 

  236. Ferruti P, Manzoni S, Richardson SCW, Duncan R, Pattrick NG, Mendichi R, Casolaro M (2000) Amphoteric linear poly(amido-amine)s as endosomolytic polymers: correlation between physicochemical and biological properties. Macromolecules 33:7793–7800

    CAS  Google Scholar 

  237. Franchini J, Ranucci E, Ferruti P, Rossi M, Cavalli R (2006) Synthesis, physicochemical properties, and preliminary biological characterizations of a novel amphoteric agmatine-based poly(amidoamine) with RGD-like repeating units. Biomacromolecules 7:1215–1222

    CAS  Google Scholar 

  238. Ferruti P, Franchini J, Bencini M, Ranucci E, Zara GP, Serpe L, Primo L, Cavalli R (2007) Prevailingly cationic agmatine-based amphoteric polyamidoamine as a nontoxic, nonhemolytic, and “stealthlike” DNA complexing agent and transfection promoter. Biomacromolecules 8:1498–1504

    CAS  Google Scholar 

  239. Cavalli R, Bisazza A, Sessa R, Primo L, Fenili F, Manfredi A, Ranucci E, Ferruti P (2010) Amphoteric agmatine containing polyamidoamines as carriers for plasmid DNA in vitro and in vivo delivery. Biomacromolecules 11:2667–2674

    CAS  Google Scholar 

  240. Strachan T, Read AP (1999) Human molecular genetics, 2nd edn. Wiley-Liss, New York, Chap 22

    Google Scholar 

  241. Gössl I, Shu L, Schlüter D, Rabe JP (2002) Molecular structure of single DNA complexes with positively charged dendronized polymers. J Am Chem Soc 124:6860–6865

    Google Scholar 

  242. Laschewsky A (2012) Recent trends in the synthesis of polyelectrolytes. Curr Opin Colloid Interface Sci 17:56–63

    CAS  Google Scholar 

  243. Schlick T, Hayes J, Grigoryev S (2012) Toward convergence of experimental studies and theoretical modeling of the chromatin fiber. J Biol Chem 287:5183–5191

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Annabelle Bertin .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bertin, A. (2013). Polyelectrolyte Complexes of DNA and Polycations as Gene Delivery Vectors. In: Müller, M. (eds) Polyelectrolyte Complexes in the Dispersed and Solid State II. Advances in Polymer Science, vol 256. Springer, Berlin, Heidelberg. https://doi.org/10.1007/12_2013_218

Download citation

Publish with us

Policies and ethics