Laboratory of Radiochemistry, Department of Chemistry, Faculty of Pharmacy, FI-00014 University of Helsinki, Finland.
Mol Pharm. 2012 Mar 5;9(3):654-63. doi: 10.1021/mp200611d. Epub 2012 Feb 1.
Rapid immune recognition and subsequent elimination from the circulation hampers the use of many nanomaterials as carriers to targeted drug delivery and controlled release in the intravenous route. Here, we report the effect of a functional self-assembled protein coating on the intravenous biodistribution of (18)F-labeled thermally hydrocarbonized porous silicon (THCPSi) nanoparticles in rats. (18)F-Radiolabeling enables the sensitive and easy quantification of nanoparticles in tissues using radiometric methods and allows imaging of the nanoparticle biodistribution with positron emission tomography. Coating with Trichoderma reesei HFBII altered the hydrophobicity of (18)F-THCPSi nanoparticles and resulted in a pronounced change in the degree of plasma protein adsorption to the nanoparticle surface in vitro. The HFBII-THCPSi nanoparticles were biocompatible in RAW 264.7 macrophages and HepG2 liver cells making their intravenous administration feasible. In vivo, the distribution of the nanoparticles between the liver and spleen, the major mononuclear phagocyte system organs in the body, was altered compared to that of uncoated (18)F-THCPSi. Identification of the adsorbed proteins revealed that certain opsonins and apolipoproteins are enriched in HFBII-functionalized nanoparticles, whereas the adsorption of abundant plasma components such as serum albumin and fibrinogen is decreased.
快速的免疫识别和随后从循环系统中的清除,阻碍了许多纳米材料作为载体用于静脉途径的靶向药物输送和控制释放。在这里,我们报告了功能化自组装蛋白涂层对(18)F 标记的热烃化多孔硅(THCPSi)纳米粒子在大鼠体内静脉生物分布的影响。(18)F 放射性标记使组织中纳米粒子的定量变得敏感和容易,并且允许使用正电子发射断层扫描术对纳米粒子的生物分布进行成像。用里氏木霉 HFBII 涂层处理改变了(18)F-THCPSi 纳米粒子的疏水性,并导致在体外纳米粒子表面上的血浆蛋白吸附程度发生明显变化。HFBII-THCPSi 纳米粒子在 RAW 264.7 巨噬细胞和 HepG2 肝细胞中具有生物相容性,使得它们的静脉给药成为可能。在体内,与未涂层的(18)F-THCPSi 相比,纳米粒子在肝脏和脾脏之间的分布(机体中主要的单核吞噬细胞系统器官)发生了改变。鉴定吸附的蛋白质表明,某些调理素和载脂蛋白在 HFBII 功能化纳米粒子中富集,而大量的血浆成分如血清白蛋白和纤维蛋白原的吸附减少。