Spontaneous penetration of gold nanoparticles through the blood brain barrier (BBB)

Abstract

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.