Sela Hagit, Cohen Hagit, Elia Paz, Zach Raya, Karpas Zeev, Zeiri Yehuda
Department of Biomedical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.
Department of Chemistry, NRCN, P.O. Box 9001, Beer-Sheva, 8419001, Israel.
J Nanobiotechnology. 2015 Oct 21;13:71. doi: 10.1186/s12951-015-0133-1.
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.
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.
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.
血脑屏障（BBB）控制着脑微环境，并限制化学物质进入中枢神经系统（CNS），从而给许多医学成像和治疗程序造成障碍。确定血脑屏障穿透可行途径的研究工作主要集中在胶束、聚合物纳米颗粒和脂质体等作为药物载体的结构上，然而，其中许多未能提供血脑屏障穿透的确切证据。在此，我们证明了金纳米颗粒（AuNPs）可穿透大鼠血脑屏障到达脑区。
向大鼠腹腔注射金纳米颗粒后，在血液、尿液、脑区和身体器官中均检测到金的存在。灌注后，脑区中金的浓度显著降低，这表明大部分金存在于静脉血中而非脑组织中。注射钠、钾或钙离子通道阻滞剂可使血脑屏障的穿透率降低一半。发现金纳米颗粒的生物半衰期为12.9±4.9小时。文中讨论了金纳米颗粒通过血脑屏障运输的可能机制。
金纳米颗粒可自发穿透血脑屏障，无需施加外部场。大部分金存在于血管中，因此需要进行灌注。离子通道阻滞剂可用于控制金纳米颗粒的运输。
