Zaloga Jan, Stapf Marcus, Nowak Johannes, Pöttler Marina, Friedrich Ralf P, Tietze Rainer, Lyer Stefan, Lee Geoffrey, Odenbach Stefan, Hilger Ingrid, Alexiou Christoph
Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius Stiftungsprofessur for Nanomedicine, University Hospital Erlangen, 91054 Erlangen, Germany.
Institute for Diagnostic and Interventional Radiology, University Hospital Jena, 07747 Jena, Germany.
Int J Mol Sci. 2015 Aug 14;16(8):19291-307. doi: 10.3390/ijms160819291.
Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEON(LA-BSA), which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION suspensions need to be purified of excess surfactant and concentrated. Conventional methods for the purification and concentration of such ferrofluids often involve high shear stress and low purification rates for macromolecules, like albumin. In this work, removal of albumin by low shear stress tangential ultrafiltration and its influence on SEON(LA-BSA) particles was studied. Hydrodynamic size, surface properties and, consequently, colloidal stability of the nanoparticles remained unchanged by filtration or concentration up to four-fold (v/v). Thereby, the saturation magnetization of the suspension can be increased from 446.5 A/m up to 1667.9 A/m. In vitro analysis revealed that cellular uptake of SEON(LA-BSA) changed only marginally. The specific absorption rate (SAR) was not greatly affected by concentration. In contrast, the maximum temperature Tmax in magnetic hyperthermia is greatly enhanced from 44.4 °C up to 64.9 °C by the concentration of the particles up to 16.9 mg/mL total iron. Taken together, tangential ultrafiltration is feasible for purifying and concentrating complex hybrid coated SPION suspensions without negatively influencing specific particle characteristics. This enhances their potential for magnetic treatment.
超顺磁性氧化铁纳米颗粒(SPIONs)常用于药物靶向、热疗及其他生物医学用途。最近,我们报道了月桂酸/白蛋白包覆的氧化铁纳米颗粒SEON(LA-BSA)的合成,该颗粒是使用过量白蛋白合成的。为了优化磁治疗应用,需要去除SPION悬浮液中的过量表面活性剂并进行浓缩。此类铁磁流体的传统纯化和浓缩方法通常涉及高剪切应力以及对白蛋白等大分子的低纯化率。在这项工作中,研究了通过低剪切应力切向超滤去除白蛋白及其对SEON(LA-BSA)颗粒的影响。通过过滤或浓缩至四倍(v/v),纳米颗粒的流体动力学尺寸、表面性质以及胶体稳定性均保持不变。由此,悬浮液的饱和磁化强度可从446.5 A/m提高至1667.9 A/m。体外分析表明,SEON(LA-BSA)的细胞摄取仅略有变化。比吸收率(SAR)受浓度影响不大。相比之下,通过将颗粒浓度提高至总铁含量为16.9 mg/mL,磁热疗中的最高温度Tmax从44.4°C大幅提高至64.9°C。综上所述,切向超滤对于纯化和浓缩复杂的混合包覆SPION悬浮液是可行的,且不会对特定颗粒特性产生负面影响。这增强了它们在磁治疗中的潜力。
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