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Cellular uptake of self-assembled phytantriol-based hexosomes is independent of major endocytic machineries
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
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2019 (Engelska)Ingår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 553, s. 820-833Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Despite increasing interests in non-lamellar liquid crystalline dispersions, such as hexosomes, for drug delivery, little is known about their interactions with cells and mechanism of cell entry. Here we examine the cellular uptake of hexosomes based on phytantriol and mannide monooleate by HeLa cells using live cell microscopy in comparison to conventional liposomes. To investigate the importance of specific endocytosis pathways upon particle internalization, we silenced regulatory proteins of major endocytosis pathways using short interfering RNA. While endocytosis plays a significant role in liposome internalization, hexosomes are not taken up via endocytosis but through a mechanism that is dependent on cell membrane tension. Biophysical studies using biomembrane models highlighted that hexosomes have a high affinity for membranes and an ability to disrupt lipid layers. Our data suggest that direct biomechanical interactions of hexosomes with membrane lipids play a crucial role and that the unique morphology of hexosomes is vital for their membrane activity. Based on these results, we propose a mechanism, where hexosomes destabilize the bilayer, allowing them to "phase through" the membrane. Understanding parameters that influence the uptake of hexosomes is critical to establish them as carrier systems that can potentially deliver therapeutics efficiently to intracellular sites of action.

Ort, förlag, år, upplaga, sidor
ACADEMIC PRESS INC ELSEVIER SCIENCE , 2019. Vol. 553, s. 820-833
Nyckelord [en]
Hexosomes, Phytantriol, Mannide monooleate, Self-assembly, Nanostructure, Endocytosis, Cell take, Biomembrane models
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
URN: urn:nbn:se:umu:diva-164503DOI: 10.1016/j.jcis.2019.06.045ISI: 000483454400086PubMedID: 31284226OAI: oai:DiVA.org:umu-164503DiVA, id: diva2:1374022
Tillgänglig från: 2019-11-28 Skapad: 2019-11-28 Senast uppdaterad: 2019-11-28Bibliografiskt granskad

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Larsson, ElinMoodie, Lindon W. K.Lundmark, RichardHubert, Madlen

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Schneider, FabianLarsson, ElinMoodie, Lindon W. K.Lundmark, RichardHubert, Madlen
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Institutionen för integrativ medicinsk biologi (IMB)Kemiska institutionen
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Journal of Colloid and Interface Science
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

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