Role of cholesterol on the transfection barriers of cationic lipid/DNA complexes
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Role of cholesterol on the transfection barriers of cationic lipid/DNA complexes. / Pozzi, Daniela; Cardarelli, Francesco; Salomone, Fabrizio; Marchini, Cristina; Amenitsch, Heinz; La Barbera, Giorgia; Caracciolo, Giulio.
I: Applied Physics Letters, Bind 105, Nr. 7, 073701, 2014.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Role of cholesterol on the transfection barriers of cationic lipid/DNA complexes
AU - Pozzi, Daniela
AU - Cardarelli, Francesco
AU - Salomone, Fabrizio
AU - Marchini, Cristina
AU - Amenitsch, Heinz
AU - La Barbera, Giorgia
AU - Caracciolo, Giulio
N1 - (Ekstern)
PY - 2014
Y1 - 2014
N2 - Most lipid formulations need cholesterol for efficient transfection, but the precise motivation remains unclear. Here, we have investigated the effect of cholesterol on the transfection efficiency (TE) of cationic liposomes made of 1,2-dioleoyl-3-trimethylammonium-propane and dioleoylphosphocholine in Chinese hamster ovary cells. The transfection mechanisms of cholesterol-containing lipoplexes have been investigated by TE, synchrotron small angle X-ray scattering, and laser scanning confocal microscopy experiments. We prove that cholesterol-containing lipoplexes enter the cells using different endocytosis pathways. Formulations with high cholesterol content efficiently escape from endosomes and exhibit a lamellar-nonlamellar phase transition in mixture with biomembrane mimicking lipid formulations. This might explain both the DNA release ability and the high transfection efficiency. These studies highlight the enrichment in cholesterol as a decisive factor for transfection and will contribute to the rational design of lipid nanocarriers with superior TE.
AB - Most lipid formulations need cholesterol for efficient transfection, but the precise motivation remains unclear. Here, we have investigated the effect of cholesterol on the transfection efficiency (TE) of cationic liposomes made of 1,2-dioleoyl-3-trimethylammonium-propane and dioleoylphosphocholine in Chinese hamster ovary cells. The transfection mechanisms of cholesterol-containing lipoplexes have been investigated by TE, synchrotron small angle X-ray scattering, and laser scanning confocal microscopy experiments. We prove that cholesterol-containing lipoplexes enter the cells using different endocytosis pathways. Formulations with high cholesterol content efficiently escape from endosomes and exhibit a lamellar-nonlamellar phase transition in mixture with biomembrane mimicking lipid formulations. This might explain both the DNA release ability and the high transfection efficiency. These studies highlight the enrichment in cholesterol as a decisive factor for transfection and will contribute to the rational design of lipid nanocarriers with superior TE.
UR - http://www.scopus.com/inward/record.url?scp=84929430382&partnerID=8YFLogxK
U2 - 10.1063/1.4892915
DO - 10.1063/1.4892915
M3 - Journal article
AN - SCOPUS:84929430382
VL - 105
JO - Applied Physics Letters
JF - Applied Physics Letters
SN - 0003-6951
IS - 7
M1 - 073701
ER -
ID: 231311193