Supramolecular Organization and siRNA Binding of Hyaluronic Acid-Coated Lipoplexes for Targeted Delivery to the CD44 Receptor
The dynamics of the formation of siRNA-lipoplexes coated with hyaluronic acid (HA) and the parameters influencing their supramolecular organization were studied. The insertion of a HA-dioleylphosphatidylethanolamine (DOPE) conjugate in the liposome structure as well as subsequent complexation with s...
Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1992. - 31(2015), 41 vom: 20. Okt., Seite 11186-94 |
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1. Verfasser: | |
Weitere Verfasser: | , , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2015
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Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Hyaluronan Receptors Lipid Bilayers RNA, Small Interfering Hyaluronic Acid 9004-61-9 |
Zusammenfassung: | The dynamics of the formation of siRNA-lipoplexes coated with hyaluronic acid (HA) and the parameters influencing their supramolecular organization were studied. The insertion of a HA-dioleylphosphatidylethanolamine (DOPE) conjugate in the liposome structure as well as subsequent complexation with siRNA increased the liposome size. Lipoplexes were around 110 nm at high ± charge ratios with a zeta potential around +50 mV and around 230 nm at low ± ratios, with a zeta potential that decreased to negative values, reaching -45 mV. The addition of the conjugate did not compromise siRNA binding to liposomes, although these nucleic acids induced a displacement of part of the HA-DOPE conjugate upon lipoplex formation, as confirmed by capillary electrophoresis. Isothermal titration calorimetry, X-ray diffraction studies, and cryo-TEM microscopy demonstrated that in addition to electrostatic interactions with siRNA a rearrangement of the lipid bilayers takes place, resulting in condensed oligolamellar vesicles. This phenomenon is dependent on the number of siRNA molecules and the degree of modification with HA. Finally, the suitable positioning of HA on the lipoplex surface and its ability to bind specifically to the CD44 receptors in a concentration-dependent manner was demonstrated by surface plasmon resonance analysis |
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Beschreibung: | Date Completed 20.04.2016 Date Revised 16.11.2017 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1520-5827 |
DOI: | 10.1021/acs.langmuir.5b01979 |