Centre of Tumor Medicine and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany.
J Microencapsul. 2012;29(1):9-20. doi: 10.3109/02652048.2011.629741. Epub 2011 Oct 31.
Red blood cells (RBCs) are natural carriers which can be used for targeted drug delivery. Conditions during loading and surface modification are essential for carrier-RBC preparation for specifically targeted drug delivery. Therefore, human RBCs were loaded with albumin and magnetic nanoparticles (NPs) by different hypotonic haemolysis procedures and compared based on loading efficiency and membrane damage. Samples were analysed by flow cytometry and confocal microscopy. The optimized loading procedure resulted in 90% albumin-loaded carrier-RBCs with <4% Annexin V binding and 263 pg iron per RBC after loading with iron oxide NPs. Albumin-loaded RBCs were subsequently surface conjugated with insulin and IgG via biotin-streptavidin. Insulin-conjugated carrier-RBCs were observed to attach and to be internalized by cultured endothelial cells. Uptake was not observed for carrier-RBCs non-specifically modified with IgG. Attachment of other peptides with high specificity will open novel opportunities for targeting various cells, tissues and for crossing biological barriers.
红细胞(RBC)是天然载体,可用于靶向药物递送。在装载和表面修饰过程中的条件对于载体-RBC 的制备对于特定的靶向药物递送至关重要。因此,通过不同的低渗溶血程序将白蛋白和磁性纳米颗粒(NPs)加载到人 RBC 上,并根据载药效率和膜损伤进行比较。通过流式细胞术和共聚焦显微镜分析样品。优化的加载程序导致 90%的白蛋白负载载体-RBC,与<4%的 Annexin V 结合,并且在负载氧化铁 NPs 后每个 RBC 中含有 263 pg 铁。随后通过生物素-链霉亲和素将胰岛素和 IgG 表面偶联到白蛋白负载的 RBC 上。观察到胰岛素偶联的载药 RBC 附着并被培养的内皮细胞内化。未观察到非特异性修饰 IgG 的载药 RBC 被内化。与具有高特异性的其他肽的附着将为靶向各种细胞、组织和跨越生物屏障开辟新的机会。