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Cationic Liposomes Carrying siRNA: Impact of Lipid Composition on Physicochemical Properties, Cytotoxicity and Endosomal Escape
Lechanteur, Anna; Sanna, Vincent; Duchemin, Amandine et al.
2018In Nanomaterials, 8 (5)
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Abstract :
[en] Abstract: In recent year, cationic liposomes have gained a lot of attention for siRNA delivery. Despite this, intracellular barriers as endosomal escape and cytosolic delivery of siRNA still represent a challeng, as well as the cytotoxicity due to cationic lipids. To address these issues, we developed four liposomal formulations, composed of two different cationic lipids (DOTAP and DC-Cholesterol) and different ratio of co-lipids (cholesterol and DOPE). The objective is to dissect these impacts on siRNA efficacy and cytotoxicity. Liposomes were complexed to siRNA at six different N/P molar ratios, physico-chemical properties were characterized, and consequently, N/P 2.5, 5 and 10 were selected for in vitro experiments. We have shown that cytotoxicity is influenced by the N/P ratio, the concentration of cationic lipid, as well as the nature of the cationic lipid. For instance, cell viability decreased by 70% with liposomes composed of DOTAP/Cholesterol/DOPE 1/0.75/0.5 at a N/P ratio 10, whereas the same formulation at a N/P ratio of 2.5 was safe. Interestingly, we have observed differences in terms of mRNA knock-down efficiency, whereas the transfection rate was quite similar for each formulation. Liposomes containing 50% of DOPE induced a mRNA silencing of around 80%. This study allowed us to highlight crucial parameters in order to develop lipoplexes which are safe, and which induce an efficient intracytoplasmic release of siRNA.
Research center :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Lechanteur, Anna  ;  Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Sanna, Vincent ;  Université de Liège - ULiège > Master spéc. pharma. ind.
Duchemin, Amandine ;  Université de Liège - ULiège > Molecular Biology of Diseases-Gene Expression & Cancer
Evrard, Brigitte  ;  Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Mottet, Denis ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Piel, Géraldine ;  Université de Liège - ULiège > Département de pharmacie > Développement de nanomédicaments
Language :
English
Title :
Cationic Liposomes Carrying siRNA: Impact of Lipid Composition on Physicochemical Properties, Cytotoxicity and Endosomal Escape
Publication date :
2018
Event name :
EuroNanomed
Event place :
Paris, France
Event date :
juillet 2018
Audience :
International
Journal title :
Nanomaterials
eISSN :
2079-4991
Publisher :
MDPI AG, Basel, Switzerland
Volume :
8
Issue :
5
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 13 February 2019

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