[en] RNAi therapeutics are promising therapeutic tools that have sparked the interest of many researchers. In an effort to provide a safe alternative to PEI, we have designed a series of new guanidinium and/or morpholino functionalized biocompatible and biodegradable polycarbonate vectors. The impact of different functions (morpholino-, guanidinium-, hydrophobic groups), of the architecture (linear homopolymer to dumbbell-shape) and of the molecular weight of these copolymers on their capacity to form polyplexes and to decrease the expression of two epigenetic regulators of gene expression, HDAC7 and HDAC5 was evaluated. The use of one of these polymers combining morpholine and guanidine functions at the ratio >1 and hydrophobic trimethylene carbonate groups showed a significant decrease of mRNA and protein level in HeLa cells, similar to PEI. These results highlight the potential of polycarbonate vectors for future in vivo application as an anti-cancer therapy.
Research Center/Unit :
Centre Interfacultaire de Recherche du Médicament - CIRM
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Frère, Antoine ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Kawalec, Michal; Université de Mons - UMONS
Tempelaar, Sarah; Université de Mons - UMONS
Peixoto, Paul ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Hendrick, Elodie ; Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Peulen, Olivier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Evrard, Brigitte ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Dubois, Philippe; Université de Mons - UMONS
Mespouille, Laetitia; Université de Mons - UMONS
Mottet, Denis ; Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Piel, Géraldine ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Language :
English
Title :
Impact of the Structure of Biocompatible Aliphatic Polycarbonates on siRNA Transfection Ability
Publication date :
January 2015
Journal title :
Biomacromolecules
ISSN :
1525-7797
eISSN :
1526-4602
Publisher :
American Chemical Society, Washington, United States - District of Columbia
Peixoto, P.; Castronovo, V.; Matheus, N.; Polese, C.; Peulen, O.; Gonzalez, A.; Boxus, M.; Verdin, E.; Thiry, M.; Dequiedt, F.; Mottet, D. Cell Death Differ. 2012, 19, 1239-52
Resnier, P.; Montier, T.; Mathieu, V.; Benoit, J. P.; Passirani, C. Biomaterials 2013, 34, 6429-43
Owens, D. E., 3rd; Peppas, N. A. Int. J. Pharm. 2006, 307, 93-102
Bertrand, N.; Leroux, J. C. J. Controlled Release 2012, 161, 152-63
Varkouhi, A. K.; Scholte, M.; Storm, G.; Haisma, H. J. J. Controlled Release 2011, 151, 220-8
Bareford, L. M.; Swaan, P. W. Adv. Drug Delivery Rev. 2007, 59, 748-58
Tietze, N.; Pelisek, J.; Philipp, A.; Roedl, W.; Merdan, T.; Tarcha, P.; Ogris, M.; Wagner, E. Oligonucleotides 2008, 18, 161-74
Cavallaro, G.; Licciardi, M.; Amato, G.; Sardo, C.; Giammona, G.; Farra, R.; Dapas, B.; Grassi, M.; Grassi, G. Int. J. Pharm. 2014, 466, 246-257
Tros de Ilarduya, C.; Sun, Y.; Duzgunes, N. Eur. J. Pharm. Sci. 2010, 40, 159-70
Kang, H. C.; Huh, K. M.; Bae, Y. H. J. Controlled Release 2012, 164, 256-264
Yousefi, A.; Storm, G.; Schiffelers, R.; Mastrobattista, E. J. Controlled Release 2013, 170, 209-18
Han, L.; Tang, C.; Yin, C. Biomaterials 2013, 34, 5317-5327
Zhu, K. J.; Hendren, R. W.; Jensen, K.; Pitt, C. G. Macromolecules 1991, 24, 1736-1740
Le Hellaye, M.; Fortin, N.; Guilloteau, J.; Soum, A.; Lecommandoux, S.; Guillaume, S. M. Biomacromolecules 2008, 9, 1924-33
Ong, Z. Y.; Fukushima, K.; Coady, D. J.; Yang, Y. Y.; Ee, P. L.; Hedrick, J. L. J. Controlled Release 2011, 152, 120-6
Allen, C.; Dos Santos, N.; Gallagher, R.; Chiu, G. N. C.; Shu, Y.; Li, W. M.; Johnstone, S. A.; Janoff, A. S.; Mayer, L. D.; Webb, M. S.; Bally, M. B. Biosci. Rep. 2002, 22, 225-250
Dominska, M.; Dykxhoorn, D. M. J. Cell Sci. 2010, 123, 1183-9
Boussif, O.; Lezoualc'h, F.; Zanta, M. A.; Mergny, M. D.; Scherman, D.; Demeneix, B.; Behr, J. P. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 7297-301
Hatakeyama, H.; Akita, H.; Kogure, K.; Oishi, M.; Nagasaki, Y.; Kihira, Y.; Ueno, M.; Kobayashi, H.; Kikuchi, H.; Harashima, H. Gene Ther. 2007, 14, 68-77
Pollard, H.; Remy, J. S.; Loussouarn, G.; Demolombe, S.; Behr, J. P.; Escande, D. J. Biol. Chem. 1998, 273, 7507-11
Moghimi, S. M.; Symonds, P.; Murray, J. C.; Hunter, A. C.; Debska, G.; Szewczyk, A. Mol. Ther. 2005, 11, 990-5
Reschner, A.; Shim, Y. H.; Dubois, P.; Delvenne, P.; Evrard, B.; Marcelis, L.; Moucheron, C.; Kirsch-De Mesmaeker, A.; Defrancq, E.; Raes, M.; Piette, J.; Collard, L.; Piel, G. J. Biomed. Nanotechnol. 2013, 9, 1432-40
Shrestha, R.; Elsabahy, M.; Florez-Malaver, S.; Samarajeewa, S.; Wooley, K. L. Biomaterials 2012, 33, 8557-8568
Goncalves, C.; Berchel, M.; Gosselin, M. P.; Malard, V.; Cheradame, H.; Jaffres, P. A.; Guegan, P.; Pichon, C.; Midoux, P. Int. J. Pharm. 2014, 460, 264-272
Rokicki, G. Prog. Polym. Sci. 2000, 25, 259-342
Lu, L.; Huang, K. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 2468-2475
Lakadamyali, M.; Rust, M. J.; Zhuang, X. Cell 2006, 124, 997-1009
Geihe, E. I.; Cooley, C. B.; Simon, J. R.; Kiesewetter, M. K.; Edward, J. A.; Hickerson, R. P.; Kaspar, R. L.; Hedrick, J. L.; Waymouth, R. M.; Wender, P. A. Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 13171-6
Tempelaar, S.; Mespouille, L.; Coulembier, O.; Dubois, P.; Dove, A. P. Chem. Soc. Rev. 2013, 42, 1312-36
Pratt, R. C.; Nederberg, F.; Waymouth, R. M.; Hedrick, J. L. Chem. Commun. (Cambridge, U. K.) 2008, 114-6
Dove, A. P.; Pratt, R. C.; Lohmeijer, B. G.; Waymouth, R. M.; Hedrick, J. L. J. Am. Chem. Soc. 2005, 127, 13798-9
Araki, J.; Zhao, C.; Ito, K. Macromolecules 2005, 38, 7524-7527
Liu, K. L.; Goh, S. H.; Li, J. Polymer 2008, 49, 732-741
Livak, K. J.; Schmittgen, T. D. Methods 2001, 25, 402-8
Yang, C.; Ong, Z. Y.; Yang, Y. Y.; Ee, P. L.; Hedrick, J. L. Macromol. Rapid Commun. 2011, 32, 1826-33
Synatschke, C. V.; Schallon, A.; Jerome, V.; Freitag, R.; Muller, A. H. Biomacromolecules 2011, 12, 4247-55
Mespouille, L.; Coulembier, O.; Kawalec, M.; Dove, A. P.; Dubois, P. Prog. Polym. Sci. 2014, 39, 1144-1164
Kiesewetter, M. K.; Scholten, M. D.; Kirn, N.; Weber, R. L.; Hedrick, J. L.; Waymouth, R. M. J. Org. Chem. 2009, 74, 9490-9496
Kiesewetter, M. K.; Shin, E. J.; Hedrick, J. L.; Waymouth, R. M. Macromolecules 2010, 43, 2093-2107
Zhang, L.; Pratt, R. C.; Nederberg, F.; Horn, H. W.; Rice, J. E.; Waymouth, R. M.; Wade, C. G.; Hedrick, J. L. Macromolecules 2010, 43, 1660-1664
Nederberg, F.; Lohmeijer, B. G. G.; Leibfarth, F.; Pratt, R. C.; Choi, J.; Dove, A. P.; Waymouth, R. M.; Hedrick, J. L. Biomacromolecules 2006, 8, 153-160
Cooley, C. B.; Trantow, B. M.; Nederberg, F.; Kiesewetter, M. K.; Hedrick, J. L.; Waymouth, R. M.; Wender, P. A. J. Am. Chem. Soc. 2009, 131, 16401-16403
Sahay, G.; Alakhova, D. Y.; Kabanov, A. V. J. Controlled Release 2010, 145, 182-95
