The role of serum complement on the organ distribution of intravenously administered poly (methyl methacrylate) nanoparticles: Effects of pre-coating with plasma and with serum complement
The role of serum complement on the organ distribution of intravenously administered poly (methyl methacrylate) nanoparticles: Effects of pre-coating with plasma and with serum complement
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DOI：
10.1023/a:1016010808522
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发表时间：
1996-07-01
影响因子：
3.7
通讯作者：
Kreuter, J
中科院分区：
文献类型：
--
作者：
Borchard, G;Kreuter, J
目的.研究了血浆蛋白和血清补体包裹的放射性标记聚甲基丙烯酸甲酯（PMMA）纳米粒在大鼠体内的器官分布，以确定血清补体对网状内皮系统（RES）器官吞噬PMMA纳米粒的影响。将PMMA-纳米颗粒用血浆蛋白或血清补体包被过夜，并注射到Wistar大鼠中。通过器官样品的闪烁计数测量纳米颗粒的体内分布。此外，在注射前通过热处理使吸附在颗粒表面的蛋白质失活，并如上所述测量颗粒的分布。而未包覆的纳米颗粒（对照组）主要由肝脏中的枯否细胞摄取，将颗粒在血浆中孵育12小时，然后热灭活，30分钟后将肝脏中的颗粒浓度降低至仅22%。120分钟后，肝脏浓度仍低于对照组，并且热灭活颗粒组的给药剂量的几乎30%存在于非RES器官和组织中。非灭活补体颗粒在30 min后以29%的浓度在肺中积累，120 min后增加至71%，而灭活补体包被的颗粒在30 min后已经达到肺浓度的70%以上。涂覆有血浆组分的颗粒能够避免被RES摄取，特别是在吸附的血浆组分热灭活之后。然而，单独的补体蛋白的吸附和热灭活不具有与用血浆蛋白包被然后热灭活相同的结果。因此，可以得出结论，血浆成分而不是补体蛋白参与RES激活和吞噬注射的纳米颗粒的过程。
Purpose. The organ distribution of radiolabeled poly (methyl methacrylate) (PMMA) nanoparticles coated with plasma proteins and serum complement in rats was studied in order to determine the effect of serum complement on the particle phagocytosis by the organs of the reticulo-endothelial system (RES).Methods. PMMA-nanoparticles were coated overnight with plasma proteins or serum complement, and injected into Wistar rats. The body distribution of nanoparticles was measured by means of scintillation counting of organ samples. In addition, proteins adsorbed to the particle surface were inactivated by heat treatment prior to injection, and the particles's distribution was measured as described above.Results. Whereas uncoated nanoparticles (control group) were mainly taken up by the Kupffer cells in the liver, incubation of the particles in plasma for 12 h followed by heat inactivation reduced the particle concentrations in the liver to merely 22% after 30 min. After 120 min, liver concentrations were still lower than the control group, and almost 30% of the administered dose of the heat-inactivated particle group was present in non-RES organs and tissues. Particles with non-inactivated complement were accumulated in the lung at concentrations of 29% after 30 min, which increased to 71% after 120 min, whereas those coated with inactivated complement reached lung concentrations above 70% already after 30 min.Conclusions. Particles coated with plasma components are able to avoid uptake by the RES, especially after heat inactivation of the plasma components adsorbed. Adsorption and heat inactivation of complement proteins alone, however, does not have the same result as coating with plasma proteins followed by heat inactivation. Therefore, it is concluded that plasma components other than complement proteins take part in the process of RES activation and phagocytosis of injected nanoparticles.