Zaloga Jan, Pöttler Marina, Leitinger Gerd, Friedrich Ralf P, Almer Gunter, Lyer Stefan, Baum Eva, Tietze Rainer, Heimke-Brinck Ralph, Mangge Harald, Dörje Frank, Lee Geoffrey, Alexiou Christoph
Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria; Center for Medical Research, Medical University of Graz, Graz, Austria.
Eur J Pharm Biopharm. 2016 Apr;101:152-62. doi: 10.1016/j.ejpb.2016.01.017. Epub 2016 Feb 8.
In this work we present a new formulation of superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic drug targeting. The particles were reproducibly synthesized from current good manufacturing practice (cGMP) - grade substances. They were surface coated using fatty acids as anchoring molecules for human serum albumin. We comprehensively characterized the physicochemical core-shell structure of the particles using sophisticated methods. We investigated biocompatibility and cellular uptake of the particles using an established flow cytometric method in combination with microwave-plasma assisted atomic emission spectroscopy (MP-AES). The cytotoxic drug mitoxantrone was adsorbed on the protein shell and we showed that even in complex media it is slowly released with a close to zero order kinetics. We also describe an in vitro proof-of-concept assay in which we clearly showed that local enrichment of this SPION-drug conjugate with a magnet allows site-specific therapeutic effects.
在这项工作中,我们提出了一种用于磁性药物靶向的超顺磁性氧化铁纳米颗粒(SPIONs)的新配方。这些颗粒由符合现行良好生产规范(cGMP)等级的物质可重复合成。它们使用脂肪酸作为人血清白蛋白的锚定分子进行表面包覆。我们使用先进方法全面表征了颗粒的物理化学核壳结构。我们结合微波等离子体辅助原子发射光谱法(MP-AES),采用既定的流式细胞术方法研究了颗粒的生物相容性和细胞摄取情况。细胞毒性药物米托蒽醌吸附在蛋白质外壳上,我们表明即使在复杂介质中,它也以接近零级动力学缓慢释放。我们还描述了一种体外概念验证试验,其中我们清楚地表明,用磁体对这种SPION-药物偶联物进行局部富集可实现位点特异性治疗效果。