To effectively applied nanomaterials (NMs) in medicine, one of the top priorities is to address a better understanding of the possible sub-organ transfer, clearance routes, and potential toxicity of the NMs in the liver and kidney. Here we explored how the surface chemistry of polyethylene glycol (PEG), chitosan (CS), and polyethylenimine (PEI) capped gold nanoparticles (GNPs) governs their sub-organ biodistribution, transfer, and clearance profiles in the liver and kidney after intravenous injection in mice. The PEG-GNPs maintained dispersion properties in vivo, facilitating passage through the liver sinusoidal endothelium and Disse space, and were captured by hepatocytes and eliminated via the hepatobiliary route. While, the agglomeration/aggregation of CS-GNPs and PEI-GNPs in hepatic Kupffer and endothelial cells led to their long-term accumulation, impeding their elimination. The gene microarray analysis shows that the accumulation of CS-GNPs and PEI-GNPs in the liver induced obvious down-regulation of Cyp4a or Cyp2b related genes, suggesting CS-GNP and PEI-GNP treatment impacted metabolic processes, while the PEI-GNP treatment is related with immune responses. This study demonstrates that manipulation of nanoparticle surface chemistry can help NPs selectively access distinct cell types and elimination pathways, which help to clinical potential of non-biodegradable NPs.

中文翻译：

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表面化学控制着功能性金纳米颗粒在肝脏和肾脏中的亚器官转移，清除和毒性

为了有效地将纳米材料（NMs）应用于医学，首要任务之一是要更好地理解NMs在肝脏和肾脏中的可能的亚器官转移，清除途径以及潜在的毒性。在这里，我们探讨了聚乙二醇（PEG），壳聚糖（CS）和聚乙烯亚胺（PEI）封端的金纳米颗粒（GNP）的表面化学如何控制静脉注射后它们在肝脏和肾脏中的亚器官生物分布，转移和清除情况在小鼠中。PEG-GNPs在体内保持分散特性，有助于通过肝正弦内皮和Disse空间，并被肝细胞捕获并通过肝胆途径消除。而，CS-GNPs和PEI-GNPs在肝Kupffer细胞和内皮细胞中的聚集/聚集导致其长期积累，阻碍了它们的清除。基因芯片分析表明，肝脏中CS-GNPs和PEI-GNPs的积累引起Cyp4a或Cyp2b相关基因的明显下调，表明CS-GNP和PEI-GNP的处理影响了代谢过程，而PEI-GNP的处理与免疫反应有关。这项研究表明，纳米粒子表面化学的操纵可以帮助NP选择性访问不同的细胞类型和消除途径，这有助于不可生物降解NP的临床潜力。提示CS-GNP和PEI-GNP治疗会影响代谢过程，而PEI-GNP治疗与免疫反应有关。这项研究表明，纳米粒子表面化学的操纵可以帮助NPs选择性访问不同的细胞类型和消除途径，这有助于不可生物降解NPs的临床潜力。提示CS-GNP和PEI-GNP治疗会影响代谢过程，而PEI-GNP治疗与免疫反应有关。这项研究表明，纳米粒子表面化学的操纵可以帮助NP选择性访问不同的细胞类型和消除途径，这有助于不可生物降解NP的临床潜力。