journal article·2013-01

Thermally sensitive polypeptide-based copolymer for DNA complexation into stable nanosized polyplexes

Emilya Ivanova, Ivaylo Dimitrov, Rahila Kozarova, Sevdalina Turmanova, Margarita Apostolova

Journal of Nanoparticle Research· Volume 15· Issue 1
Publisher page

Abstract

Gene therapy based on non-viral synthetic delivery vectors has attracted much attention in the past two decades. However, it is still in clinical trial stages, mainly due to the lack of safe and efficient delivery vehicles. Herein, we report on the synthesis and DNA complexation ability of novel, hybrid copolymer comprising poly(N-isopropylacrylamide) (PNIPAm) block with poly(ethylene glycol) (PEG) side chains and a polycationic block of poly(l-lysine) (PLLys). The copolymer was synthesized in a two-step procedure. In the first step, a thermally sensitive PNIPAm-g-PEG copolymer with terminal ammonium hydrochloride group was prepared. The second step involves controlled ring-opening polymerization of Z-l-lysine N-carboxyanhydride initiated by the PNIPAm-g-PEG macroinitiator. The hybrid copolymer obtained show high ability to condense DNA into stable polyplexes with sizes below 100 nm. Cytotoxicity evaluation of both hybrid copolymer and its polyplex with DNA indicates that it might be a good candidate for gene-delivery applications.
Source: openaire · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: RNA Interference and Gene Delivery · Advanced Polymer Synthesis and Characterization · Nanoparticle-Based Drug Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (34)

Show source-provided references
1. Baum C, Kustikova O, Modlich U, Li Z, Fehze B (2006) Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors. Hum Gene Ther 17:253–26310.1089/hum.2006.17.253 ↗
2. Check E (2002) Gene therapy: a tragic setback. Nature 420:116–11810.1038/420116a ↗
3. Cho YW, Kim Y-D, Park K (2003) Polycation gene delivery systems: escape from endosomes to cytosol. J Pharm Pharmacol 55:721–73410.1211/002235703765951311 ↗
4. Choi YH, Liu F, Kim J-S, Choi YK, Park YS, Kim SW (1998) Polyethylene glycol-grafted poly-l-lysine as polymeric gene carrier. J Control Release 54:39–4810.1016/S0168-3659(97)00174-0 ↗
5. Dash PR, Read ML, Barrett LB, Wolfert MA, Seymour LW (1999) Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery. Gene Ther 6:643–65010.1038/sj.gt.3300843 ↗
6. de Ilarduya CT, Sun Y, Düzgüneş N (2010) Gene delivery by lipoplexes and polyplexes. Eur J Pharm Sci 40:159–17010.1016/j.ejps.2010.03.019 ↗
7. Dimitrov I, Schlaad H (2003) Synthesis of nearly monodisperse polystyrene-polypeptide block copolymers via polymerisation of N-carboxyanhydrides. Chem Commun 23:2944–294510.1039/B308990H ↗
8. Dimitrov I, Berlinova I, Vladimirov N (2006) Synthesis of poly(oxyethylene)-poly(Z-l-lysine) hybrid graft copolymers. Macromolecules 39:2423–242610.1021/ma0524981 ↗
9. Dimitrov I, Trzebicka B, Müller AHE, Dworak A, Tsvetanov C (2007) Thermosensitive water-soluble copolymers with doubly responsive reversibly interacting entities. Prog Polym Sci 32:1275–134310.1016/j.progpolymsci.2007.07.001 ↗
10. Dimitrov I, Berlinova I, Iliev P, Vladimirov N (2008) Controlled synthesis of peptide-based amphiphilic copolymers. Macromolecules 41:1045–104910.1021/ma071798a ↗
11. Dimitrov I, Petrova E, Kozarova R, Apostolova M, Tsvetanov C (2011) A mild and versatile approach for DNA encapsulation. Soft Matter 7:8002–800410.1039/c1sm05805c ↗
12. Du F-S, Wang Y, Zhang R, Li Z-C (2010) Intelligent nucleic acid delivery systems based on stimuli-responsive polymers. Soft Matter 6:835–84810.1039/B915020J ↗
13. Gil ES, Hudson SM (2004) Stimuli-responsive polymers and their bioconjugates. Prog Polym Sci 29:1173–122210.1016/j.progpolymsci.2004.08.003 ↗
14. 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–S8210.1098/rsif.2009.0260 ↗
15. Grisham J (2000) Inquiry into gene therapy widens. Nat Biotechnol 18:254–25510.1038/73673 ↗
16. Hinrichs WLJ, Schuurmans-Nieuwenbroek NME, van de Wetering P, Hennink WE (1999) Thermosensitive polymers as carriers for DNA delivery. J Control Release 60:249–25910.1016/S0168-3659(99)00075-9 ↗
17. Itaka K, Harada A, Nakamura K, Kawaguchi H, Kataoka K (2002) Evaluation by fluorescence resonance energy transfer of the stability of nonviral gene delivery vectors under physiological conditions. Biomacromolecules 3:841–84510.1021/bm025527d ↗
18. Kakizawa Y, Kataoka K (2002) Block copolymer micelles for delivery of gene and related compounds. Adv Drug Deliv Rev 54:203–22210.1016/S0169-409X(02)00017-0 ↗
19. Karmali PP, Chaudhuri A (2007) Cationic liposomes as non-viral carriers of gene medicines: resolved issues, open questions, and future promises. Med Res Rev 27:696–72210.1002/med.20090 ↗
20. Kurisawa M, Yokoyama M, Okano T (2000) Gene expression control by temperature with thermo-responsive polymeric gene carriers. J Control Release 69:127–13710.1016/S0168-3659(00)00297-2 ↗
21. Lavigne MD, Pennadam SS, Ellis J, Yates LL, Alexander C, Górecki DC (2007) Enhanced gene expression through temperature profile-induced variations in molecular architecture of thermoresponsive polymer vectors. J Gene Med 9:44–5410.1002/jgm.992 ↗
22. LePecq J-B, Paoletti C (1967) A fluorescent complex between ethidium bromide and nucleic acids. Physical–chemical characterization. J Mol Biol 27:87–10610.1016/0022-2836(67)90353-1 ↗
23. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–6310.1016/0022-1759(83)90303-4 ↗
24. O’Rorke S, Keeney M, Pandit A (2010) Non-viral polyplexes: scaffold mediated delivery for gene therapy. Prog Polym Sci 35:441–45810.1016/j.progpolymsci.2010.01.005 ↗
25. Oupický D, Reschel T, Koňak Č, Oupická 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 36:6863–687210.1021/ma034039a ↗
26. Poché D, Moore M, Bowles J (1999) An unconventional method for purifying the N-carboxyanhydride derivatives of γ-alkyl-l-glutamates. Synth Commun 29:843–85410.1080/00397919908086042 ↗
27. Roques C, Fattal E, Fromes Y (2009) Comparison of toxicity and transfection efficiency of amphiphilic block copolymers and polycationic polymers in striated muscles. J Gene Med 11:240–24910.1002/jgm.1304 ↗
28. Schaffer DV, Fidelman NA, Dan N, Lauffenburger DA (2000) Vector unpacking as a potential barrier for receptor-mediated polyplex gene delivery. Biotechnol Bioeng 67:598–60610.1002/(SICI)1097-0290(20000305)67:5<598::AID-BIT10>3.0.CO;2-G ↗
29. Shen Z, Shi B, Zhang H, Bi J, Dai S (2012) Exploring low-positively charged thermosensitive copolymers as gene delivery vectors. Soft Matter 8:1385–139410.1039/C1SM06262J ↗
30. Soliman M, Allen S, Davies MC, Alexander C (2010) Responsive polyelectrolyte complexes for triggered release of nucleic acid therapeutics. Chem Commun 46:5421–543310.1039/c0cc00794c ↗
31. Trentin D, Hubbell J, Hall H (2005) Non-viral gene delivery for local and controlled DNA release. J Control Release 102:263–27510.1016/j.jconrel.2004.09.029 ↗
32. Vinogradov SV, Bronich TK, Kabanov AV (1998) Self-assembly of polyamine-poly(ethylene glycol) copolymers with phosphorothioate oligonucleotides. Bioconjug Chem 9:805–81210.1021/bc980048q ↗
33. Wong SY, Pelet JM, Putnam D (2007) Polymer systems for gene delivery—past, present, and future. Prog Polym Sci 32:799–83710.1016/j.progpolymsci.2007.05.007 ↗
34. Zintchenko A, Ogris M, Wagner E (2006) Temperature dependent gene expression induced by PNIPAM-based copolymers: potential of hyperthermia in gene transfer. Bioconjug Chem 17:766–77210.1021/bc050292z ↗