[en] Lipid-based nanocarriers such as liposomes or lipid nanoparticles (LNPs) have demonstrated high interest in delivering genetic material. This has been recently emphasized by the approval of Onpattro® and COVID-19 vaccines. PEGylation is known to provide lipid-based nanocarriers with stealth properties, but it also leads to reduced cellular uptake and endosomal escape, and to the production of anti-PEG antibodies causing accelerated blood clearance (ABC) and hypersensitivity reactions (HSR). This work highlights the great potential of amphiphilic poly(N-methyl-N-vinylacetamide) (PNMVA) derivatives as alternatives to lipid-PEG for post-insertion into lipoplexes and pre-insertion into LNPs designed for siRNA delivery. PNMVA compounds with different degrees of polymerization and hydrophobic segments, such as octadecyl and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), were synthesized. Among them, DSPE-PNMVA efficiently integrated into lipoplex and LNP membranes and prevented protein corona formation around these lipid carriers, exhibiting stealth properties comparable to DSPE-PEG. However, unlike DSPE-PEG, DSPE-PNMVA24 showed no adverse impact on lipoplexes cell uptake and endosomal escape. In in vivo study with mice, DSPE-PNMVA24 lipoplexes demonstrated no liver accumulation, indicating good stealth properties, extended circulation time after a second dose, reduced immunological reaction, and no systemic pro-inflammatory response. Safety of DSPE-PNMVA24 was confirmed at the cellular level and in animal models of zebrafish and mice. Overall, DSPE-PNMVA is an advantageous substitute to DSPE-PEG for siRNA delivery, offering comparable stealth and toxicity properties while improving efficacy of the lipid-based carriers by minimizing the dilemma effect and reducing immunological reactions, meaning no ABC or HSR effects.
Research Center/Unit :
CESAM - Complex and Entangled Systems from Atoms to Materials - ULiège CERM - Center for Education and Research on Macromolecules - ULiège CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège GIGA - Cancer - ULiège GIGA - Molecular Biology of Diseases - ULiège GIGA - Platform Zebrafish Facility & Transgenics - ULiège [ BE ]
Berger, Manon ✱; University of Liège [ULiège] - Center for Interdisciplinary Research on Medicines [CIRM] - Laboratory of Pharmaceutical Technology and Biopharmacy - Belgium
Toussaint, François ✱; University of Liège [ULiège] - Complex and Entangled Systems from Atoms to Materials [CESAM] - Research Unit, Center for Education and Research on Macromolecules [CERM] - Belgium
Djemaa, Sanaa Ben ✱; University of Liège [ULiège] - GIGA-Molecular Biology of Diseases - Laboratory of Gene Expression and Cancer [GEC] - Belgium
Maquoi, Erik ; University of Liège [ULiège] - GIGA-Cancer - Laboratory of Tumor and Development Biology - Belgium
Pendeville-Samain, Hélène ; University of Liège [ULiège] - GIGA - Platform Zebrafish Facility and Transgenics - Belgium
Evrard, Brigitte ; University of Liège [ULiège] - Center for Interdisciplinary Research on Medicines [CIRM] - Laboratory of Pharmaceutical Technology and Biopharmacy - Belgium
Jérôme, Christine ; University of Liège [ULiège] - Complex and Entangled Systems from Atoms to Materials [CESAM] - Research Unit, Center for Education and Research on Macromolecules [CERM] - Belgium
Chain, Jeanne Leblond; University of Bordeaux - Centre National de la Recherche Scientifique [CNRS] - Institut national de la santé et de la recherche médicale [INSERM] - Laboratory " Acides nucléiques : Régulations naturelles et artificielles [ARNA] " - France
Lechanteur, Anna ; University of Liège [ULiège] - Center for Interdisciplinary Research on Medicines [CIRM] - Laboratory of Pharmaceutical Technology and Biopharmacy - Belgium
Mottet, Denis ✱; University of Liège [ULiège] - GIGA-Molecular Biology of Diseases - Laboratory of Gene Expression and Cancer [GEC] - Belgium
Debuigne, Antoine ✱; University of Liège [ULiège] - Complex and Entangled Systems from Atoms to Materials [CESAM] - Research Unit, Center for Education and Research on Macromolecules [CERM] - Belgium
Piel, Géraldine ✱; University of Liège [ULiège] - Center for Interdisciplinary Research on Medicines [CIRM] - Laboratory of Pharmaceutical Technology and Biopharmacy - Belgium
✱ These authors have contributed equally to this work.
Language :
English
Title :
Poly(N-methyl‐N‐vinylacetamide): a strong alternative to PEG for lipid‐based nanocarriers delivering siRNA
Publication date :
2024
Journal title :
Advanced Healthcare Materials
ISSN :
2192-2640
eISSN :
2192-2659
Publisher :
Wiley, Germany
Pages :
e2302712
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
The "LIPEGALT" project
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique Actions de Recherche Concertées [ARC] - ULiège Walloon region
Funding text :
The research was supported by the Wallonia-Brussels Federation (grant for Concerted Research Actions, LIPEGALT project, ULiège). Authors would like to thank Luc Duwez and Olivier Nivelles (GIGA-Mouse facility, University of Liege) for their help in mice experiments. Our data of flow cytometry and toxicity in Zebrafish were obtained with the assistance of the GIGA-Flow Cytometry and GIGA-Zebrafish facilities of the University of Liege. A.D. and DM are FNRS Senior Research Associate. They thank FNRS for financial support.
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Bibliography
C. H. Albertsen, J. A. Kulkarni, D. Witzigmann, M. Lind, K. Petersson, J. B. Simonsen, Adv. Drug Delivery Rev. 2022, 188, 114416.
F. P. Polack, S. J. Thomas, N. Kitchin, J. Absalon, A. Gurtman, S. Lockhart, J. L. Perez, G. Pérez Marc, E. D. Moreira, C. Zerbini, R. Bailey, K. A. Swanson, S. Roychoudhury, K. Koury, P. Li, W. V. Kalina, D. Cooper, R. W. Frenck Jr, L. L. Hammitt, O. Tureci, H. Nell, A. Schaefer, S. Unal, D. B. Tresnan, S. Mather, P. R. Dormitzer, U. Sahin, K. U. Jansen, W. C. Gruber, N. Engl. J. Med. 2020, 383, 2603.
D. Adams, A. Gonzalez-Duarte, W. D. O'Riordan, C.-C. Yang, M. Ueda, A. V. Kristen, I. Tournev, H. H. Schmidt, T. Coelho, J. L. Berk, K.-P. Lin, G. Vita, S. Attarian, V. Polante-Bordeneuve, M. M. Mezei, J. M. Campistol, J. Buades, T. H. Brannagam 3rd, B. J. Kim, J. Oh, Y. Parman, Y. Sekijima, P. N. Hawkins, S. D. Solomon, M. Polydefkis, P. J. Dyck, P. J. Gandhi, S. Goyal, J. Chen, A. L. Strahs, et al., N. Engl. J. Med. 2018, 379, 11.
L. R. Baden, H. M. El Sahly, B. Essink, K. Kotloff, S. Frey, R. Novak, D. Diemert, S. A. Spector, N. Rouphael, C. B. Creech, J. Mcgettigan, S. Khetan, N. Segall, J. Solis, A. Brosz, C. Fierro, H. Schwartz, K. Neuzil, L. Corey, P. Gilbert, H. Janes, D. Follmann, M. Marovich, J. Mascola, L. Polakowski, J. Ledgerwood, B. S. Graham, H. Bennett, R. Pajon, C. Knightly, et al., N. Engl. J. Med. 2021, 384, 403.
J. Rüger, S. Ioannou, D. Castanotto, C. A. Stein, Trends Pharmacol. Sci. 2020, 41, 27.
T. Thanh, H. Thi, E. J. A. Suys, J. S. Lee, D. H. Nguyen, K. D. Park, N. P. Truong, Vaccines 2021, 8, 359.
Y. Sakurai, H. Hatakeyama, Y. Sato, M. Hyodo, H. Akita, H. Harashima, Mol. Ther. 2013, 21, 1195.
J. S. Suk, Q. Xu, N. Kim, J. Hanes, L. M. Ensign, Adv. Drug Delivery Rev. 2016, 99, 28.
Q. Yang, S. K. Lai, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2015, 7, 655.
T. Ishida, M. Harada, X. Y. Wang, M. Ichihara, K. Irimura, H. Kiwada, J. Controlled Release 2005, 105, 305.
A. S. Abu Lila, H. Kiwada, T. Ishida, J. Controlled Release 2013, 172, 38.
A. S. Nosova, O. O. Koloskova, A. A. Nikonova, V. A. Simonova, V. V. Smirnov, D. Kudlay, M. R. Khaitov, MedChemComm 2019, 10, 369.
F. Zahednezhad, M. Saadat, H. Valizadeh, P. Zakeri-Milani, B. Baradaran, J. Controlled Release 2019, 305, 194.
T. Suzuki, Y. Suzuki, T. Hihara, K. Kubara, K. Kondo, K. Hyodo, K. Yamazaki, T. Ishida, H. Ishihara, Int. J. Pharm. 2020, 588, 119792.
S. Zalba, T. L. M. Ten Hagen, C. Burgui, M. J. Garrido, J. Controlled Release 2022, 351, 22.
A. A. D'souza, R. Shegokar, Expert Opin. Drug Deliv. 2016, 13, 1257.
H. Hatakeyama, H. Akita, H. Harashima, Biol. Pharm. Bull. 2013, 36, 892.
D. Vllasaliu, R. Fowler, S. Stolnik, Expert Opin. Drug Deliv. 2014, 11, 139.
Y. Xia, J. Tian, X. Chen, Biomaterials 2016, 79, 56.
M. Kanamala, B. D. Palmer, H. Ghandehari, W. R. Wilson, Z. Wu, Pharm. Res. 2018, 35, 154.
M. Dominska, D. M. Dykxhoorn, J. Cell Sci. 2010, 123, 1183.
Y. Luo, Y. Hong, L. Shen, F. Wu, X. Lin, AAPS PharmSciTech 2021, 22, 34.
J. Kopecek, J. Yang, Adv. Drug Delivery Rev. 2020, 156, 40.
M. Kurakula, G. S. N. K. Rao, J. Drug Delivery Sci. Technol. 2020, 60, 102046.
M. Kurakula, G. S. N. Koteswara Rao, Eur. Polym. J. 2020, 136, 109919.
W. B. Liechty, D. R. Kryscio, B. V. Slaughter, N. A. Peppas, Annu. Rev. Chem. Biomol. Eng. 2010, 1, 149.
N. Roka, O. Kokkorogianni, P. Kontoes-Georgoudakis, I. Choinopoulos, M. Pitsikalis, Polymers (Basel) 2022, 14, 701.
M. S. B. Husain, A. Gupta, B. Y. Alashwal, S. Sharma, Energy Sources Part A 2018, 40, 2388.
M. Teodorescu, M. Bercea, S. Morariu, Biotechnol. Adv. 2019, 37, 109.
M. Teodorescu, M. Bercea, Polym. – Plast. Technol. Eng. 2015, 54, 923.
V. Pautu, E. Lepeltier, A. Mellinger, J. Riou, A. Debuigne, C. Jérôme, N. Clere, C. Passirani, Cancers 2021, 13, 2028.
P. H. Kierstead, H. Okochi, V. J. Venditto, T. C. Chuong, S. Kivimae, J. M. J. Fréchet, F. C. Szoka, J. Controlled Release 2015, 213, 1.
V. P. Torchilin, T. S. Levchenko, K. R. Whiteman, A. A. Yaroslavov, A. M. Tsatsakis, A. K. Rizos, E. V. Michailova, M. I. Shtilman, Biomaterials 2001, 22, 3035.
I. A. Yamskov, A. N. Kuskov, K. K. Babievsky, B. B. Berezin, M. A. Krayukhina, N. A. Samoylova, V. E. Tikhonov, M. I. Shtilman, Appl. Biochem. Microbiol. 2008, 44, 624.
M. Berger, F. Toussaint, S. B. Djemaa, J. Laloy, H. Pendeville, B. Evrard, C. Jerôme, A. Lechanteur, D. Mottet, A. Debuigne, G. Piel, J. Controlled Release 2023, 361, 87.
W. Fan, S. Yamago, Angew. Chem., Int. Ed. 2019, 58, 7113.
M. Dréan, P. Guégan, C. Detrembleur, C. Jérôme, J. Rieger, A. Debuigne, Macromolecules 2016, 49, 4817.
A. Debuigne, A. N. Morin, A. Kermagoret, Y. Piette, C. Detrembleur, C. Jérôme, R. Poli, Chem. Eur. J. 2012, 18, 12834.
M. Dréan, A. Debuigne, C. Goncalves, C. Jérôme, P. Midoux, J. Rieger, P. Guégan, Biomacromolecules 2017, 18, 440.
A. Dupre–Demorsy, O. Coutelier, M. Destarac, C. Nadal, V. Bourdon, T. Ando, H. Ajiro, Macromolecules 2022, 55, 1127.
P. R. Cullis, M. J. Hope, Mol. Ther. 2017, 25, 1467.
W. Viricel, S. Poirier, A. Mbarek, R. M. Derbali, G. Mayer, J. Leblond, Nanoscale 2017, 9, 31.
M. Langlais, O. Coutelier, M. Destarac, Macromolecules 2018, 51, 4315.
M. Destarac, C. Kalai, A. Wilczewska, L. Petit, E. Van Gramberen, S. Z. Zard, ACS Symp. Ser. 2006, 944, 564.
T. John, Z. X. Voo, C. Kubeil, B. Abel, B. Graham, L. Spiccia, L. L. Martin, MedChemComm 2017, 8, 1112.
A. Mechler, S. Praporski, K. Atmuri, M. Boland, F. Separovic, L. L. Martin, Biophys. J. 2007, 93, 3907.
M. C. Dixon, J. Biomol. Tech. 2008, 19, 151.
G. Sauerbrey, Z. Med. Phys. 1959, 155, 206.
M. Berger, M. Degey, J. Leblond Chain, E. Maquoi, B. Evrard, A. Lechanteur, G. Piel, Pharmaceutics 2023, 15, 597.
H.-R. Jia, Y.-X. Zhu, Q.-Y. Duan, Z. Chen, F.-G. Wu, J. Controlled Release 2019, 311, 301.
K. Y. Lee, G. H. Jang, C. H. Byun, M. Jeun, P. C. Searson, K. H. Lee, Biosci. Rep. 2017, 37, BSR2010199.
A. Ledoux, A. St-Gelais, E. Cieckiewicz, O. Jansen, A. Bordignon, B. Illien, N. Di Giovanni, A. Marvilliers, F. Hoareau, H. Pendeville, J. Quetin-Leclercq, M. Frédérich, J. Nat. Prod. 2017, 80, 1750.
S. Sieber, P. Grossen, P. Uhl, P. Detampel, W. Mier, D. Witzigmann, J. Huwyler, Nanomed. Nanotechnol. Biol. Med. 2019, 17, 82.
A. Debuigne, G. Piel, D. Mottet, F. Toussaint, M. Berger, S. Ben Djemaa, A. Lechanteur, Polymer Derivatives and Their Use as Lipid Nanoparticle Modifiers 2023, EP23171538, 4.
A. Lechanteur, T. Furst, B. Evrard, P. Delvenne, P. Hubert, G. Piel, Int. J. Pharm. 2015, 483, 268.
A. Lechanteur, T. Furst, B. Evrard, P. Delvenne, G. Piel, P. Hubert, Mol. Pharmaceutics 2017, 14, 1706.
T. Furst, G. R. Dakwar, E. Zagato, A. Lechanteur, K. Remaut, B. Evrard, K. Braeckmans, G. Piel, J. Controlled Release 2016, 236, 68.
T. Furst, V. Bettonville, E. Farcas, A. Frere, A. Lechanteur, B. Evrard, M. Fillet, G. Piel, A.-C. Servais, Electrophoresis 2016, 37, 2685.
A. Lechanteur, T. Furst, B. Evrard, P. Delvenne, P. Hubert, G. Piel, Eur. J. Pharm. Sci. 2016, 93, 493.
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