Elimination Pathways of Nanoparticles
Elimination Pathways of Nanoparticles
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DOI：
10.1021/acsnano.9b01383
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发表时间：
2019-05-01
期刊：
影响因子：
17.1
通讯作者：
Chan, Warren C. W.
中科院分区：
文献类型：
--
作者：
Poon, Wilson;Zhang, Yi-Nan;Chan, Warren C. W.
了解纳米颗粒如何从体内消除是其成功临床转化所必需的。许多用于体内医学应用的有前途的纳米颗粒制剂是大的（> 5.5nm）且不可生物降解的，因此它们不能通过肾脏消除。这些纳米颗粒的拟议途径是肝胆消除，但其运输尚未得到充分研究。在这里，我们探讨了决定通过肝胆途径消除纳米颗粒的障碍。肝胆消除途径通常通过以下途径：（1）肝窦，（2）Disse间隙，（3）肝细胞，（4）胆管，（5）肠和（6）体外。我们发现纳米颗粒与肝非实质细胞（例如，枯否细胞和肝窦内皮细胞）决定消除命运。该路线的每一步都包含可以隔离和化学或物理改变纳米颗粒的细胞，这会影响它们的粪便消除。我们发现，去除枯否细胞使粪便消除增加了>10倍。结合我们的结果与先前的研究，我们可以开始建立一个系统的纳米粒子消除途径，因为它涉及到粒径和其他设计参数。这对于设计医学上有用的和可翻译的纳米技术至关重要。
Understanding how nanoparticles are eliminated from the body is required for their successful clinical translation. Many promising nanoparticle formulations for in vivo medical applications are large (>5.5 nm) and nonbiodegradable, so they cannot be eliminated renally. A proposed pathway for these nanoparticles is hepatobiliary elimination, but their transport has not been well-studied. Here, we explored the barriers that determined the elimination of nanoparticles through the hepatobiliary route. The route of hepatobiliary elimination is usually through the following pathway: (1) liver sinusoid, (2) space of Disse, (3) hepatocytes, (4) bile ducts, (5) intestines, and (6) out of the body. We discovered that the interaction of nanoparticles with liver nonparenchymal cells (e.g., Kupffer cells and liver sinusoidal endothelial cells) determines the elimination fate. Each step in the route contains cells that can sequester and chemically or physically alter the nanoparticles, which influences their fecal elimination. We showed that the removal of Kupffer cells increased fecal elimination by >10 times. Combining our results with those of prior studies, we can start to build a systematic view of nanoparticle elimination pathways as it relates to particle size and other design parameters. This is critical to engineering medically useful and translatable nanotechnologies.