Innate immuno-response to nanoparticle uptake in liver and spleen mimics pathogen infection

Systemically administered nanoparticles (NPs) designed for biomedical applications are retained in liver and spleen where they become rapidly phagocyted by tissue macrophages leading to inflammation. To gain insight into the NP-immune cell interaction in liver spleen and lungs, we followed the distribution of molybdenum nanoparticles (MoNPs) <i>in vivo</i> by X-Ray Fluorescence Imaging (XRF) and examined the NP-macrophage interaction and physiological response in these organs. XRF imaging showed that intravenously administered MoNPs transiently accumulate in lungs, liver, and spleen. This leads to increments in the number of Kupffer cells (KC), natural killer (NK) cells, oxidative stress, and inflammation. Macrophage phenotype switched from pro- to an anti-inflammatory. In parallel genes with immunoregulatory and cytoprotective functions were expressed to maintain homeostasis. Nanoparticle uptake in spleen was operated by CD169/Siglec1 splenic macrophages indicating initiation of a secondary immune response. Silica coating reduced nanoparticle toxicity. The innate immunoresponse to NP uptake in liver and spleen is similar to viral or bacterial infections in these organs. A possible secondary immunoresponse to NPs can be primed in spleen aided by CD169/Siglec1 splenic macrophages. Silica coating of metal NPs tunes down this response.

用于生物医学应用的全身给药纳米颗粒（nanoparticles, NPs）会在肝脏与脾脏中潴留，并被组织巨噬细胞快速吞噬，进而引发炎症反应。为深入解析纳米颗粒与免疫细胞在肝、脾及肺组织中的相互作用机制，本研究通过X射线荧光成像（X-Ray Fluorescence Imaging, XRF）追踪了钼纳米颗粒（molybdenum nanoparticles, MoNPs）的体内分布，并检测了上述器官内纳米颗粒与巨噬细胞的相互作用及生理响应。X射线荧光成像结果显示，静脉注射的MoNPs会在肺、肝和脾脏中出现暂时性蓄积。该蓄积过程可导致库普弗细胞（Kupffer cells, KC）、自然杀伤细胞（natural killer cells, NK）数量增加，同时诱发氧化应激与炎症反应；巨噬细胞表型也会从促炎表型向抗炎表型转变。与此同时，机体会表达具有免疫调节与细胞保护功能的基因以维持体内稳态。脾脏内的纳米颗粒摄取由CD169/Siglec1阳性脾脏巨噬细胞介导，这提示次级免疫反应的启动。二氧化硅涂层可降低纳米颗粒的毒性。机体对肝、脾中纳米颗粒摄取的固有免疫应答，与这些器官发生病毒或细菌感染时的免疫应答模式相似。针对纳米颗粒的潜在次级免疫应答可在脾脏中被CD169/Siglec1阳性脾脏巨噬细胞诱导启动，而金属纳米颗粒的二氧化硅涂层可减弱该免疫应答过程。