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Cellular uptake of self-assembled phytantriol-based hexosomes is independent of major endocytic machineries
Ludwig Maximilians Univ Munchen, Dept Pharm Pharmaceut Technol & Biopharm, Butenandtstr 5-13, DE-81377 Munich, Germany.
Tech Univ Munich, Walter Schottky Inst, Phys Dept, Coulombwall 4a, DE-85748 Garching, Germany;Tech Univ Munich, Walter Schottky Inst, Inst Adv Study, Coulombwall 4a, DE-85748 Garching, Germany.ORCID iD: 0000-0002-3146-4815
Tech Univ Munich, Soft Matter Phys Grp, Phys Dept, James Franck Str 1, DE-85748 Garching, Germany.
Umea Univ, Dept Integrat Med Biol, Johan Bures Vag 12, SE-90187 Umea, Sweden.
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2019 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 553, p. 820-833Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE , 2019. Vol. 553, p. 820-833
Keywords [en]
Hexosomes, Phytantriol, Mannide monooleate, Self-assembly, Nanostructure, Endocytosis, Cell uptake, Biomembrane models
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-394188DOI: 10.1016/j.jcis.2019.06.045ISI: 000483454400086PubMedID: 31284226OAI: oai:DiVA.org:uu-394188DiVA, id: diva2:1359464
Funder
EU, European Research Council, 256270EU, European Research Council, 724261Swedish Cancer Society, CAN2014/746Swedish Cancer Society, CAN 2017/735German Research Foundation (DFG)Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-10-09Bibliographically approved

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Moodie, Lindon W. K.

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