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Membrane fusogenic high-density lipoprotein nanoparticles.
- Source :
-
Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2019 Oct 01; Vol. 1861 (10), pp. 183008. Date of Electronic Publication: 2019 Jun 15. - Publication Year :
- 2019
-
Abstract
- Membrane fusion under mildly acidic pH occurs naturally during viral infection in cells and has been exploited in the field of nanoparticle-mediated drug delivery to circumvent endosomal entrapment of the cargo. Herein, we aimed to confer virus-like fusogenic activity to HDL in the form of a ca. 10-nm disc comprising a discoidal lipid bilayer and two copies of a lipid-binding protein at the edge. A series of HDL mutants were prepared with a mixture of three lipids and a cell-penetrating peptide (TAT, penetratin, or Arg8) fused to the protein. In a lipid-mixing assay with anionic liposomes at pH 5.5, one HDL mutant showed the fusogenic activity higher than known fusogenic liposomes. In live mammalian cells, this HDL mutant showed high plasma membrane-binding activity in the presence of serum independent of pH. In the absence of serum, a mildly acidic pH dependency for binding to the plasma membrane and the subsequent lipid mixing between them was observed for this mutant. We propose a novel strategy to develop HDL-based drug carriers by taking advantage of the HDL lipid/protein composite structure.<br /> (Copyright © 2019. Published by Elsevier B.V.)
- Subjects :
- Amino Acid Sequence
Animals
Cell Line, Tumor
Cell Membrane metabolism
Cell-Penetrating Peptides
Endosomes metabolism
Humans
Hydrogen-Ion Concentration
Lipid Bilayers metabolism
Lipids
Lipoproteins, HDL metabolism
Liposomes metabolism
Membrane Fusion drug effects
Membranes metabolism
Peptide Fragments chemistry
Lipoproteins, HDL chemistry
Membrane Fusion physiology
Nanoparticles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1879-2642
- Volume :
- 1861
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Biomembranes
- Publication Type :
- Academic Journal
- Accession number :
- 31207206
- Full Text :
- https://doi.org/10.1016/j.bbamem.2019.06.007