不同的磁性纳米粒子涂层决定了它们在静脉注射到小鼠体内 15 个月后的体内降解动力学。

BACKGROUND: The surface coating of iron oxide magnetic nanoparticle (MNPs) drives their intracellular trafficking and degradation in endolysosomes, as well as dictating other cellular outcomes. As such, we assessed whether MNP coatings might influence their biodistribution, their accumulation in certain organs and their turnover therein, processes that must be understood in vivo to optimize the design of nanoformulations for specific therapeutic/diagnostic needs. RESULTS: In this study, three different MNP coatings were analyzed, each conferring the identical 12 nm iron oxide cores with different physicochemical characteristics: 3-aminopropyl-triethoxysilane (APS), dextran (DEX), and dimercaptosuccinic acid (DMSA). When the biodistribution of these MNPs was analyzed in C57BL/6 mice, they all mainly accumulated in the spleen and liver one week after administration. The coating influenced the proportion of the MNPs in each organ, with more APS-MNPs accumulating in the spleen and more DMSA-MNPs accumulating in the liver, remaining there until they were fully degraded. The changes in the physicochemical properties of the MNPs (core size and magnetic properties) was also assessed during their intracellular degradation when internalized by two murine macrophage cell lines. The decrease in the size of the MNPs iron core was influenced by their coating and the organ in which they accumulated. Finally, MNP degradation was analyzed in the liver and spleen of C57BL/6 mice from 7 days to 15 months after the last intravenous MNP administration. CONCLUSIONS: The MNPs degraded at different rates depending on the organ and their coating, the former representing the feature that was fundamental in determining the time they persisted. In the liver, the rate of degradation was similar for all three coatings, and it was faster than in the spleen. This information regarding the influence of coatings on the in vivo degradation of MNPs will help to choose the best coating for each biomedical application depending on the specific clinical requirements.

背景：氧化铁磁性纳米粒子（MNPs）的表面涂层决定了它们在内溶酶体中的细胞内运输和降解，以及其他细胞结果。因此，我们评估了 MNP 涂层是否会影响它们的生物分布、在某些器官中的积累及其在其中的转化，这些过程必须在体内进行理解，以优化针对特定治疗/诊断需求的纳米制剂的设计。

结果：在这项研究中，分析了三种不同的 MNP 涂层，每种涂层都赋予相同的 12nm 氧化铁核，但具有不同的物理化学特性：3-氨丙基三乙氧基硅烷（APS）、葡聚糖（DEX）和二巯基丁二酸（DMSA）。当这些 MNPs 的生物分布在 C57BL/6 小鼠中进行分析时，它们在给药后一周主要积聚在脾脏和肝脏中。涂层影响了 MNPs 在每个器官中的比例，APS-MNPs 更多地积聚在脾脏中，DMSA-MNPs 更多地积聚在肝脏中，直到它们完全降解。还评估了两种小鼠巨噬细胞系内吞后 MNPs 体内降解过程中 MNPs 的物理化学性质（核大小和磁性）的变化。MNPs 核大小的减小受其涂层和积聚的器官影响。最后，在最后一次静脉内 MNP 给药后 7 天至 15 个月，在 C57BL/6 小鼠的肝脏和脾脏中分析了 MNP 降解。

结论：根据器官和涂层的不同，MNPs 的降解速度也不同，前者是决定它们持续时间的基本特征。在肝脏中，三种涂层的降解速度相似，且快于脾脏。关于涂层对 MNPs 体内降解影响的这一信息将有助于根据具体的临床需求，为每个生物医学应用选择最佳的涂层。