Mechanism of hard-nanomaterial clearance by the liver.
Mechanism of hard-nanomaterial clearance by the liver.
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DOI：
10.1038/nmat4718
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发表时间：
2016-11
期刊：
影响因子：
41.2
通讯作者：
Chan, Warren C. W.
中科院分区：
文献类型：
--
作者：
Tsoi, Kim M.;MacParland, Sonya A.;Ma, Xue-Zhong;Spetzler, Vinzent N.;Echeverri, Juan;Ouyang, Ben;Fadel, Saleh M.;Sykes, Edward A.;Goldaracena, Nicolas;Kaths, Johann M.;Conneely, John B.;Alman, Benjamin A.;Selzner, Markus;Ostrowski, Mario A.;Adeyi, Oyedele A.;Zilman, Anton;McGilvray, Ian D.;Chan, Warren C. W.
肝脏和脾是转化纳米药物的主要生物学障碍，因为它们隔离了大多数给药的纳米材料，并阻止了向患病组织的传递。在这里，我们研究了给予硬纳米材料的血液清除机制与血流动力学、器官微结构和细胞表型的关系。我们发现，纳米材料进入和穿过肝脏时，速度会减慢1000倍，导致纳米材料与肝细胞的相互作用是外周细胞的7.5倍。在肝脏中，库普弗细胞(84.8%±6.4%)、肝B细胞(81.5%±9.3%)和肝窦内皮细胞(64.6%±13.7%)与聚乙二醇化量子点相互作用，而脾巨噬细胞(25.4±10.1%)因表型不同而较少。另外两种类型的纳米材料和五种不同的表面化学物质的吸收模式相似。克服靶外纳米材料堆积的潜在新策略可能包括操纵器官内血流动力学和调节细胞表型以改变肝细胞相互作用。
The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture, and cellular phenotype. We found that nanomaterial velocity reduces 1000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8%±6.4%), hepatic B cells (81.5±9.3%), and liver sinusoidal endothelial cells (64.6±13.7%) interacted with administered PEGylated quantum dots but splenic macrophages took up less (25.4±10.1%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating cellular phenotype to alter hepatic cell interaction.
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