Department of Chemistry, University of Massachusetts , 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.
ACS Nano. 2016 May 24;10(5):5536-42. doi: 10.1021/acsnano.6b02086. Epub 2016 May 12.
Surface chemistry plays a deciding role in nanoparticle biodistribution, yet very little is known about how surface chemistry influences the suborgan distributions of nanomaterials. Here, using quantitative imaging based on laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), we demonstrate that surface charge dictates the suborgan distributions of nanoparticles in the kidney, liver, and spleen of mice intravenously injected with functionalized gold nanoparticles. Images of the kidney show that positively charged nanoparticles accumulate extensively in the glomeruli, the initial stage in filtering for the nephron, suggesting that these nanoparticles may be filtered by the kidney at a different rate than the neutral or negatively charged nanoparticles. We find that positively and negatively charged nanoparticles accumulate extensively in the red pulp of the spleen. In contrast, uncharged nanoparticles accumulate in the white pulp and marginal zone of the spleen to a greater extent than the positively or negatively charged nanoparticles. Moreover, these uncharged nanoparticles are also more likely to be found associated with Kupffer cells in the liver. Positively charged nanoparticles accumulate extensively in liver hepatocytes, whereas negatively charged nanoparticles show a broader distribution in the liver. Together these observations suggest that neutral nanoparticles having 2 nm cores may interact with the immune system to a greater extent than charged nanoparticles, highlighting the value of determining the suborgan distributions of nanomaterials for delivery and imaging applications.
表面化学在纳米颗粒的生物分布中起着决定性的作用,但人们对表面化学如何影响纳米材料的亚器官分布知之甚少。在这里,我们使用基于激光烧蚀电感耦合等离子体质谱(LA-ICP-MS)的定量成像技术,证明了表面电荷决定了经静脉注射功能化金纳米颗粒的小鼠的肾脏、肝脏和脾脏中纳米颗粒的亚器官分布。肾脏图像显示,带正电荷的纳米颗粒在肾小球中广泛积累,肾小球是肾单位过滤的初始阶段,这表明这些纳米颗粒可能以不同于中性或带负电荷的纳米颗粒的速率被肾脏过滤。我们发现带正电荷和带负电荷的纳米颗粒在脾脏的红髓中广泛积累。相比之下,不带电荷的纳米颗粒在脾脏的白髓和边缘区的积累程度比带正电荷或带负电荷的纳米颗粒更大。此外,这些不带电荷的纳米颗粒也更有可能与肝脏中的库普弗细胞相关联。带正电荷的纳米颗粒在肝实质细胞中广泛积累,而带负电荷的纳米颗粒在肝脏中的分布更广。这些观察结果表明,具有 2nm 核的中性纳米颗粒可能比带电纳米颗粒更能与免疫系统相互作用,这凸显了确定纳米材料亚器官分布对于输送和成像应用的价值。
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