Polymeric vehicles for transport and delivery of DNA via cationic micelle template method
- 136 Downloads
- 1 Citations
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.
Keywords
Micelleplexes Polymer carriers DNA Gene deliveryNotes
Funding information
This work was supported by the Bulgarian National Science Fund (Project T02/7-2014).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
References
- 1.Mulligan R (1993) The basic science of gene therapy. Science 260:926–932CrossRefGoogle 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 17:1–9CrossRefGoogle Scholar
- 3.Cross D, Burmester JK (2006) Gene therapy for cancer treatment: past, present and future. Clin Med Res 4:218–227CrossRefGoogle Scholar
- 4.Mintzer M, Simanek E (2009) Nonviral vectors for gene delivery. Chem Rev 109:259–302CrossRefGoogle Scholar
- 5.Pichon C, Billiet L, Midoux P (2010) Chemical vectors for gene delivery: uptake and intracellular trafficking. Curr Opin Biotechnol 21:640–645CrossRefGoogle Scholar
- 6.Yue Y, Wu C (2013) Progress and perspectives in developing polymeric vectors for in vitro gene delivery. Biomater Sci 1:152–170CrossRefGoogle Scholar
- 7.De Smedt SC, Demeester J, Hennink WE (2000) Cationic polymer based gene delivery systems. Pharm Res 17:113–126CrossRefGoogle Scholar
- 8.Park TG, Jeong JH, Kim SW (2006) Current status of polymeric gene delivery systems. Adv Drug Deliv Rev 58:467–486CrossRefGoogle Scholar
- 9.Wong S, Pelet J, Putnam D (2007) Polymer systems for gene delivery—past, present, and future. Prog Polym Sci 32:799–837CrossRefGoogle 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 5:345–354CrossRefGoogle Scholar
- 11.Lasic DD, Strey H, Stuart MCA, Podgornik R, Frederik PM (1997) The structure of dna–liposome complexes. J Am Chem Soc 119:832–833CrossRefGoogle 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 9:102–109CrossRefGoogle 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 311:275–281CrossRefGoogle Scholar
- 14.Pissuwan D, Niidome T, Cortie MB (2011) The forthcoming applications of gold nanoparticles in drug and gene delivery systems. J Control Release 149:65–71CrossRefGoogle Scholar
- 15.O’Rorke S, Keeney M, Pandit A (2010) Non-viral polyplexes: scaffold mediated delivery for gene therapy. Prog Polym Sci 35:441–458CrossRefGoogle Scholar
- 16.Tros de Ilarduya C, Sunb Y, Düzgünes N (2010) Gene delivery by lipoplexes and polyplexes. Eur J Pharm Sci 40:159–170CrossRefGoogle Scholar
- 17.Lungwitz U, Breunig M, Blunk T, Gopferich A (2005) Polyethylenimine-based non-viral gene delivery systems. Eur J Pharm Biopharm 60:247–266CrossRefGoogle 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 140:40–46CrossRefGoogle 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 15:1358–1368CrossRefGoogle Scholar
- 20.Agarwal S, Zhang Y, Maji S, Greiner A (2012) PDMAEMA based gene delivery materials. Mater Today 15:388–393CrossRefGoogle 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 65:1234–1270CrossRefGoogle 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 17:354–361CrossRefGoogle 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 209:77–87CrossRefGoogle Scholar
- 24.Zhang Y, Liu Y, Sen S, Král P, Gemeinhart RA (2015) Charged group surface accessibility determines micelleplexes formation and cellular interaction. Nano 7:7559–7564Google 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 331:167–175CrossRefGoogle Scholar
- 26.Vonarbourg A, Passirani C, Saulnier P, Benoit JP (2006) Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials 27:4356–4373CrossRefGoogle 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 54:5166–5173CrossRefGoogle Scholar
- 28.Haladjova E, Rangelov S, Tsvetanov C, Simon P (2014) Preparation of polymeric nanocapsules via nano-sized poly(methoxydiethyleneglycol methacrylate) colloidal templates. Polymer 55:1621–1627CrossRefGoogle 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 15:4377–4395CrossRefGoogle 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 68:65–73CrossRefGoogle Scholar
- 31.Dimitrov IV, Petrova EB, Kozarova RG, Apostolova MD, Tsvetanov CB (2011) A mild and versatile approach for DNA encapsulation. Soft Matter 7:8002–8004CrossRefGoogle Scholar
- 32.Haladjova E, Rangelov S, Tsvetanov CB, Pispas S (2012) DNA encapsulation via nanotemplates from cationic block copolymer micelles. Soft Matter 8:2884–2889CrossRefGoogle Scholar
- 33.Petrov PD, Ivanova NI, Apostolova MD, Tsvetanov CB (2013) Biodegradable polymer network encapsulated polyplex for DNA delivery. RSC Adv 3:3508–3511CrossRefGoogle 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 23:4080–4084CrossRefGoogle 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 17:2691–2700CrossRefGoogle Scholar
- 36.Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63CrossRefGoogle 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 84:27–37CrossRefGoogle 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 30:8193–8200CrossRefGoogle 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 31:10017–10025CrossRefGoogle 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 115:844–860CrossRefGoogle Scholar
- 41.Dias RS, Lindman B (2008) DNA interaction with polymers and surfactants. John Wiley & Sons, Inc., Hoboken, CrossRefGoogle 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 17:3580–3590CrossRefGoogle Scholar