Spontaneous penetration of gold nanoparticles through the blood brain barrier (BBB).
BACKGROUND
The blood brain barrier (BBB) controls the brain microenvironment and limits penetration of the central nervous system (CNS) by chemicals, thus creating an obstacle to many medical imaging and treatment procedures. Research efforts to identify viable routes of BBB penetration have focused on structures such as micelles, polymeric nanoparticles and liposomes as drug carriers, however, many of them failed to provide unequivocal proof of BBB penetration. Here we proved that gold nanoparticles (AuNPs) penetrate the BBB in rats to reach brain regions.


RESULTS
Injection of AuNPs to the abdominal cavity of rats resulted in levels of gold found in blood, urine, brain regions and body organs. After perfusion the concentration of gold in brain regions diminished dramatically indicating that most of the gold was in venous blood and not in the brain tissues. Injection of Na, K or Ca ion channel blockers reduced BBB penetration by half. A biological half-life of 12.9 ± 4.9 h was found for the gold nanoparticles. Possible mechanisms for the transport of AuNPs through the BBB are discussed.


CONCLUSIONS
BBB penetration by AuNPs is spontaneous without the application of an external field. A major amount of gold resides in blood vessels therefore perfusion required. Ion channel blockers can be used to control the transport of AuNPs.
Department of Biomedical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel. hagitsel@post.bgu.ac.il.|Department of Chemistry, NRCN, P.O. Box 9001, Beer-Sheva, 8419001, Israel. hagitsel@post.bgu.ac.il.
Hagit
H
Sela
The State of Israel Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Beer-Sheva Mental Health Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel. hagitc@bgu.ac.il.
Hagit
H
Cohen
Department of Biomedical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel. pazel@post.bgu.ac.il.
Paz
P
Elia
Department of Biomedical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel. raya970@gmail.com.
Raya
R
Zach
Department of Chemistry, NRCN, P.O. Box 9001, Beer-Sheva, 8419001, Israel. zeevkar44@gmail.com.
Zeev
Z
Karpas
Department of Biomedical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel. yehuda.zeiri@gmail.com.|Department of Chemistry, NRCN, P.O. Box 9001, Beer-Sheva, 8419001, Israel. yehuda.zeiri@gmail.com.
Yehuda
Y
Zeiri
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D006046:Gold / Q000737:chemistry*; D007700:Kinetics; D008027:Light; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D010477:Perfusion; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D006046:Gold