The effect of nanoparticle size on the probability to cross the blood-brain barrier: An in-vitro endothelial cell model

Malka Shilo, Anat Sharon, Koby Baranes, Menachem Motiei, Jean Paul M. Lellouche, Rachela Popovtzer

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


Background: During the last decade nanoparticles have gained attention as promising drug delivery agents that can transport through the blood brain barrier. Recently, several studies have demonstrated that specifically targeted nanoparticles which carry a large payload of therapeutic agents can effectively enhance therapeutic agent delivery to the brain. However, it is difficult to draw definite design principles across these studies, owing to the differences in material, size, shape and targeting agents of the nanoparticles. Therefore, the main objective of this study is to develop general design principles that link the size of the nanoparticle with the probability to cross the blood brain barrier. Specifically, we investigate the effect of the nanoparticle size on the probability of barbiturate coated GNPs to cross the blood brain barrier by using bEnd.3 brain endothelial cells as an in vitro blood brain barrier model. Results: The results show that GNPs of size 70 nm are optimal for the maximum amount of gold within the brain cells, and that 20 nm GNPs are the optimal size for maximum free surface area. Conclusions: These findings can help understand the effect of particle size on the ability to cross the blood brain barrier through the endothelial cell model, and design nanoparticles for brain imaging/therapy contrast agents.

Original languageEnglish
Article number19
JournalJournal of Nanobiotechnology
Issue number1
StatePublished - 4 Mar 2015

Bibliographical note

Funding Information:
This work was supported by the Israel Cancer Research Fund (ICRF), by Teva Pharmaceutical Industries Ltd. under the Israeli National Network of Excellence in Neuroscience (NNE) established by Teva and by the Christians for Israel Chair in Medical Research.

Publisher Copyright:
© 2015 Shilo et al.


  • BEnd.3 cells
  • Barbiturate
  • Blood-brain Barrier
  • Gold Nanoparticles
  • Nanoparticle size


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