Skip to main content
Log in

Polymeric vehicles for transport and delivery of DNA via cationic micelle template method

  • Original Contribution
  • Published:
Colloid and Polymer Science Aims and scope Submit manuscript

Abstract

This work describes the preparation of polymeric non-viral system for transport and delivery of nucleic acids. An amphiphilic poly(2-(dimethylamino)ethyl methacrylate)-block-poly(ε-caprolactone)-block-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA20-b-PCL70-b-PDMAEMA20) triblock copolymer was synthesized and used for formation of cationic micelles and subsequent complexation with DNA. Next, a protective polymer coating on the complex surface and removal of copolymer from the particle interior were conducted. In this way, polymer nanocapsules containing DNA molecules were obtained. The synthesized polymer, cationic micelles, complexes, and polymer capsules were investigated by proton nuclear magnetic resonance, gel permeation chromatography, dynamic and electrophoretic light scattering, and transmission electron microscopy. In vitro cytotoxicity assessment of the different systems revealed very good tolerance to human cells.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  2. Wong L, Goodhead L, Prat C, Mitrophanous K, Kingsman S, Mazarakis N (2006) Lentivirus-mediated gene transfer to the central nervous system: therapeutic and research applications. Hum Gene Ther 17:1–9

    Article  CAS  Google Scholar 

  3. Cross D, Burmester JK (2006) Gene therapy for cancer treatment: past, present and future. Clin Med Res 4:218–227

    Article  CAS  Google Scholar 

  4. Mintzer M, Simanek E (2009) Nonviral vectors for gene delivery. Chem Rev 109:259–302

    Article  CAS  Google Scholar 

  5. Pichon C, Billiet L, Midoux P (2010) Chemical vectors for gene delivery: uptake and intracellular trafficking. Curr Opin Biotechnol 21:640–645

    Article  CAS  Google Scholar 

  6. Yue Y, Wu C (2013) Progress and perspectives in developing polymeric vectors for in vitro gene delivery. Biomater Sci 1:152–170

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  8. Park TG, Jeong JH, Kim SW (2006) Current status of polymeric gene delivery systems. Adv Drug Deliv Rev 58:467–486

    Article  CAS  Google Scholar 

  9. Wong S, Pelet J, Putnam D (2007) Polymer systems for gene delivery—past, present, and future. Prog Polym Sci 32:799–837

    Article  CAS  Google Scholar 

  10. Huang CY, Uno T, Murphy JE, Lee S, Hamer JD, Escobedo JA, Cohen FE, Radhakrishnan R, Dwarki V, Zuckermann RN (1998) Lipitoids-novel cationic lipids for cellular delivery of plasmid DNA in vitro. Chem Biol 5:345–354

    Article  CAS  Google Scholar 

  11. Lasic DD, Strey H, Stuart MCA, Podgornik R, Frederik PM (1997) The structure of dna–liposome complexes. J Am Chem Soc 119:832–833

    Article  CAS  Google Scholar 

  12. Scherer F, Anton M, Schillinger U, Henke J, Bergemann C, Krüger A, Gänsbachera B, Plank C (2002) Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Ther 9:102–109

    Article  CAS  Google Scholar 

  13. Mykhaylyk O, Vlaskou D, Tresilwised N, Pithayanukul P, Möller W, Plank C (2007) Magnetic nanoparticle formulations for DNA and siRNA delivery. J Magn Magn Mater 311:275–281

    Article  CAS  Google Scholar 

  14. Pissuwan D, Niidome T, Cortie MB (2011) The forthcoming applications of gold nanoparticles in drug and gene delivery systems. J Control Release 149:65–71

    Article  CAS  Google Scholar 

  15. O’Rorke S, Keeney M, Pandit A (2010) Non-viral polyplexes: scaffold mediated delivery for gene therapy. Prog Polym Sci 35:441–458

    Article  Google Scholar 

  16. Tros de Ilarduya C, Sunb Y, Düzgünes N (2010) Gene delivery by lipoplexes and polyplexes. Eur J Pharm Sci 40:159–170

    Article  CAS  Google Scholar 

  17. Lungwitz U, Breunig M, Blunk T, Gopferich A (2005) Polyethylenimine-based non-viral gene delivery systems. Eur J Pharm Biopharm 60:247–266

    Article  CAS  Google Scholar 

  18. Deng R, Yue Y, Jin F, Chen Y, Kung HF, Lin MCM, Wu C (2009) Revisit the complexation of PEI and DNA—how to make low cytotoxic and highly efficient PEI gene transfection non-viral vectors with a controllable chain length and structure? J Control Release 140:40–46

    Article  CAS  Google Scholar 

  19. Ivanova E, Dimitrov I, Kozarova R, Turmanova S, Apostolova M (2013) Thermally sensitive polypeptide-based copolymer for DNA complexation into stable nanosized polyplexes. J Nanopart Res 15:1358–1368

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. Buschmann MD, Merzouki A, Lavertu M, Thibault M, Jean M, Darras V (2013) Chitosans for delivery of nucleic acids. Adv Drug Deliv Rev 65:1234–1270

    Article  CAS  Google Scholar 

  22. Osawa S, Osada K, Hiki S, Dirisala A, Ishii T, Kataoka K (2016) Polyplex micelles with double-protective compartments of hydrophilic shell and thermoswitchable palisade of poly(oxazoline)-based block copolymers for promoted gene transfection. Biomacromolecules 17:354–361

    Article  CAS  Google Scholar 

  23. Li J, Chen Q, Zha Z, Li H, Toh K, Dirisala A, Matsumoto Y, Osada K, Kataoka K, Ge Z (2015) Ternary polyplex micelles with PEG shells and intermediate barrier to complexed DNA cores for efficient systemic gene delivery. J Control Release 209:77–87

    Article  CAS  Google Scholar 

  24. Zhang Y, Liu Y, Sen S, Král P, Gemeinhart RA (2015) Charged group surface accessibility determines micelleplexes formation and cellular interaction. Nano 7:7559–7564

    CAS  Google Scholar 

  25. De Wolf HK, Snel CJ, Verbaan FJ, Schiffelers RM, Hennink WE, Storm G (2007) Effect of cationic carriers on the pharmacokinetics and tumor localization of nucleic acids after intravenous administration. Int J Pharm 331:167–175

    Article  Google Scholar 

  26. Vonarbourg A, Passirani C, Saulnier P, Benoit JP (2006) Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials 27:4356–4373

    Article  CAS  Google Scholar 

  27. Toncheva N, Tsvetanov C, Rangelov S, Trzebicka B, Dworak A (2013) Hydroxyl end-functionalized poly(2-isopropyl oxazoline)s used as nano-sized colloidal templates for preparation of hollow polymeric nanocapsules. Polymer 54:5166–5173

    Article  CAS  Google Scholar 

  28. Haladjova E, Rangelov S, Tsvetanov C, Simon P (2014) Preparation of polymeric nanocapsules via nano-sized poly(methoxydiethyleneglycol methacrylate) colloidal templates. Polymer 55:1621–1627

    Article  CAS  Google Scholar 

  29. Haladjova E, Toncheva-Moncheva N, Apostolova MD, Trzebicka B, Dworak A, Petrov P, Dimitrov I, Rangelov S, Tsvetanov CB (2014) Polymeric nanoparticle engineering: from temperature-responsive polymer mesoglobules to gene delivery systems. Biomacromolecules 15:4377–4395

    Article  CAS  Google Scholar 

  30. Trzebicka B, Haladjova E, Otulakowski Ł, Oleszko N, Wałach W, Libera M, Rangelov S, Dworak A (2015) Hybrid nanoparticles obtained from mixed mesoglobules. Polymer 68:65–73

    Article  CAS  Google Scholar 

  31. Dimitrov IV, Petrova EB, Kozarova RG, Apostolova MD, Tsvetanov CB (2011) A mild and versatile approach for DNA encapsulation. Soft Matter 7:8002–8004

    Article  CAS  Google Scholar 

  32. Haladjova E, Rangelov S, Tsvetanov CB, Pispas S (2012) DNA encapsulation via nanotemplates from cationic block copolymer micelles. Soft Matter 8:2884–2889

    Article  CAS  Google Scholar 

  33. Petrov PD, Ivanova NI, Apostolova MD, Tsvetanov CB (2013) Biodegradable polymer network encapsulated polyplex for DNA delivery. RSC Adv 3:3508–3511

    Article  CAS  Google Scholar 

  34. Ivanova ED, Ivanova NI, Apostolova MD, Turmanova SC, Dimitrov IV (2013) Polymer gene delivery vectors encapsulated in thermally sensitive bioreducible shell. Bioorg Med Chem Lett 23:4080–4084

    Article  CAS  Google Scholar 

  35. Szweda R, Trzebicka B, Dworak A, Otulakowski L, Kosowski D, Hertlein J, Haladjova E, Rangelov S, Szweda D (2016) Smart polymeric nanocarriers of Met-enkephalin. Biomacromolecules 17:2691–2700

    Article  CAS  Google Scholar 

  36. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  Google Scholar 

  37. Grancharov G, Gancheva V, Kyulavska M, Momekova D, Momekov G, Petrov P (2016) Functional multilayered polymeric nanocarriers for delivery of mitochondrial targeted anticancer drug curcumin. Polymer 84:27–37

    Article  CAS  Google Scholar 

  38. Haladjova E, Rangelov S, Tsvetanov CB, Posheva V, Peycheva E, Maximova V, Momekova D, Mountrichas G, Pispas S, Bakandritsos A (2014) Enhanced gene expression promoted by hybrid magnetic/cationic block copolymer micelles. Langmuir 30:8193–8200

    Article  CAS  Google Scholar 

  39. Haladjova E, Halacheva S, Posheva V, Peycheva E, Moskova-Doumanova V, Topouzova-Hristova T, Doumanov J, Rangelov S (2015) Comblike polyethylenimine-based polyplexes: balancing toxicity, cell internalization, and transfection efficiency via polymer chain topology. Langmuir 31:10017–10025

    Article  CAS  Google Scholar 

  40. Lee H, Son SH, Sharma R, Won YY (2011) A discussion of the pH-dependent protonation behaviors of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(ethylenimine-ran-2-ethyl-2-oxazoline) (P(EI-r-EOz)). J Phys Chem B 115:844–860

    Article  CAS  Google Scholar 

  41. Dias RS, Lindman B (2008) DNA interaction with polymers and surfactants. John Wiley & Sons, Inc., Hoboken,

    Book  Google Scholar 

  42. Mees M, Haladjova E, Momekova D, Momekov G, Shestakova PS, Tsvetanov CB, Hoogenboom R, Rangelov S (2016) Partially hydrolyzed poly(n-propyl-2-oxazoline): synthesis, aqueous solution properties, and preparation of gene delivery systems. Biomacromolecules 17:3580–3590

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Bulgarian National Science Fund (Project T02/7-2014).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Petar Petrov.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Haladjova, E., Kyulavska, M., Doumanov, J. et al. Polymeric vehicles for transport and delivery of DNA via cationic micelle template method. Colloid Polym Sci 295, 2197–2205 (2017). https://doi.org/10.1007/s00396-017-4193-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00396-017-4193-7

Keywords

Navigation