Fullerene Nanoparticles Selectively Enter Oxidation-Damaged Cerebral Microvessel Endothelial Cells and Inhibit JNK-Related Apoptosis

详细信息    查看全文

• 作者：Fang Lao ; Long Chen ; Wei Li ; Cuicui Ge ; Ying Qu ; Quanmei Sun ; Yuliang Zhao ; Dong Han ; Chunying Chen
• 刊名：ACS Nano
• 出版年：2009
• 出版时间：November 24, 2009
• 年：2009
• 卷：3
• 期：11
• 页码：3358-3368
• 年卷期：0
• ISSN：1936-086X

文摘

There is a dearth in fundamental cellular-level understanding of how nanoparticles interact with the cells of the blood brain barrier (BBB), particularly under the oxidative environment. The apoptosis of cerebral microvessel endothelial cells (CMECs) induced by oxidative stress injury plays a key role in the dysfunction of BBB. By use of CMECs as an in vitro BBB model, we show for the first time that C₆₀(C(COOH)₂)₂ nanoparticles can selectively enter oxidized CMECs rather than normal cells, and maintain CMECs integrity by attenuating H₂O₂-induced F-actin depolymerization via the observation of several state-of-the art microscopic techniques. Additionally, we have found that C₆₀(C(COOH)₂)₂ nanoparticles greatly inhibit the apoptosis of CMECs induced by H₂O₂, which is related to their modulation of the JNK pathway. C₆₀(C(COOH)₂)₂ nanoparticles can regulate several downstream signaling events related to the JNK pathway, including reduction of JNK phosphorylation, activation of activator protein 1 (AP-1) and caspase-3, and inhibition of polyADP-ribose polymerase (PARP) cleavage and mitochondrial cytochrome c release. Our results indicate that C₆₀(C(COOH)₂)₂ nanoparticles possess a novel ability of selectively entering oxidation-damaged cerebral endothelial cells rather than normal endothelial cells and then protecting them from apoptosis.