Department of Zoology, Faculty of Science, Sohag University, Sohag 82524, Egypt.
Chemistry Department, Animal Health Research Institute, Agricultural Research Center, Sohag, Egypt.
Acta Histochem. 2022 Jul;124(5):151907. doi: 10.1016/j.acthis.2022.151907. Epub 2022 May 25.
Polyethylene glycol (PEG) is widely used polymer in the field of pharmaceutics, particularly in which related to drug delivery systems (DDS). Surface coating of the nanoparticles (NPs) with PEG (i.e. pegylation) adds novel characteristics that make their use in vivo more effective with lower cytotoxicity. The biodistribution profiles, reaction, and fate of PEG-coated NPs in vivo still unclear and need more detailed studies. Here in this study, we prepared PEG-coated iron oxide nanoclusters (PEG-coated IONCs) to investigate their biodistribution profiles and reactions in spleen after intravenous injection time-dependently. Using Prussian blue staining method as specific histochemical reaction for iron detection in the tissues, the PEG-coated IONCs were observed in a higher ratio in spleen red pulp after 1 day of injection but decreased time-dependently after 10 days and 20 days. Interestingly, PEG-coated IONCs moved from red pulp into the white pulp specially after 20 days of injection. After long time exposure (20 days), higher amount of PEG-coated IONCs was observed in the center of spleen white pulp follicle. Using histological staining, the reaction of PEG-coated IONCs with splenocytes or immune cells induced cellular abnormalities such as, nucleic acid damages, induction of megakaryocytes number, and sever vacuolation in the white pulp area specially after 20 days of injection. Histochemically, the localization of PEG-coated IONCs in the splenic parenchyma induced the level of the collagen fibers particularly after 1 day and 10 days of injection. Interestingly, cellular abnormalities in the splenic red pulp as well as collagen levels decreased after 20 days of injection due to the clearance of PEG-coated IONCs from this area. This data indicated that cytotoxicity produced by the reaction of PEG-coated IONCs in the spleen are reversible specially after 20 days of in the intravenous injection. Understanding the detailed mechanism of the fate and reaction of the coated nanomaterials after intravenous injection is important to design effective and safe DDS based NPs.
聚乙二醇（PEG）在药剂学领域被广泛应用，特别是在药物传递系统（DDS）中。纳米颗粒（NPs）表面涂覆 PEG（即 PEG 化）增加了新的特性，使其在体内更有效且细胞毒性更低。PEG 涂层 NPs 在体内的生物分布、反应和命运仍不清楚，需要更详细的研究。在这里，我们制备了 PEG 涂层的氧化铁纳米团簇（PEG 涂层的 IONCs），以研究它们在静脉注射后随时间变化在脾脏中的生物分布和反应。使用普鲁士蓝染色法作为组织中铁检测的特异性组织化学反应，我们观察到在注射后 1 天，PEG 涂层的 IONCs 在脾脏红髓中的比例更高，但在 10 天和 20 天后随时间依赖性降低。有趣的是，PEG 涂层的 IONCs 在注射后 20 天从红髓转移到白髓。长时间暴露（20 天）后，在脾脏白髓滤泡中心观察到更多的 PEG 涂层的 IONCs。使用组织学染色，PEG 涂层的 IONCs 与脾细胞或免疫细胞的反应导致细胞异常，如核酸损伤、巨核细胞数量增加以及白髓区域的严重空泡化，特别是在注射后 20 天。组织化学染色显示，PEG 涂层的 IONCs 在脾脏实质中的定位特别是在注射后 1 天和 10 天诱导胶原纤维水平升高。有趣的是，由于脾脏红髓中 PEG 涂层的 IONCs 被清除，注射后 20 天脾红髓中的细胞异常和胶原水平降低。这些数据表明，PEG 涂层的 IONCs 在脾脏中的反应产生的细胞毒性在静脉注射后 20 天是可逆的。了解静脉注射后涂层纳米材料的命运和反应的详细机制对于设计基于 NPs 的有效和安全的 DDS 非常重要。
