Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier

Sci Rep. 2017 Jul 10;7(1):4970. doi: 10.1038/s41598-017-05148-9.


Vitamin E is one of the most important natural antioxidants, protecting polyunsaturated fatty acids in the membranes of cells. Among different chemical isoforms assimilated from dietary regimes, RRR-α-tocopherol is the only one retained in higher animals. This is possible thanks to α-Tocopherol Transfer Protein (α-TTP), which extracts α-tocopherol from endosomal compartments in liver cells, facilitating its distribution into the body. Here we show that, upon binding to its substrate, α-TTP acquires tendency to aggregation into thermodynamically stable high molecular weight oligomers. Determination of the structure of such aggregates by X-ray crystallography revealed a spheroidal particle formed by 24 protein monomers. Oligomerization is triggered by refolding of the N-terminus. Experiments with cultured cell monolayers demonstrate that the same oligomers are efficiently transported through an endothelial barrier (HUVEC) and not through an epithelial one (Caco-2). Discovery of a human endogenous transport protein with intrinsic capability of crossing endothelial tissues opens to new ways of drug delivery into the brain or other tissues protected by endothelial barriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Crystallography, X-Ray
  • Endosomes / metabolism*
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Models, Molecular
  • Nanoparticles / chemistry
  • Protein Aggregates
  • Protein Conformation
  • Protein Folding
  • Protein Multimerization
  • Protein Stability
  • Thermodynamics
  • alpha-Tocopherol / metabolism*


  • Carrier Proteins
  • Protein Aggregates
  • alpha-tocopherol transfer protein
  • alpha-Tocopherol