Mohammad Faruq, Al-Lohedan Hamad A
Surfactant Research Chair, Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Surfactant Research Chair, Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Mater Sci Eng C Mater Biol Appl. 2017 Jul 1;76:692-700. doi: 10.1016/j.msec.2017.03.162. Epub 2017 Mar 20.
In this, we developed superparamagnetic iron oxide nanoparticles (SPIONs) to be appropriate for the diagnosis and treatment of cancer cells by means of magnetic resonance imaging (MRI) and magnetically controlled hyperthermia/drug delivery (respectively). For the preparation of composite, we started with SPIONs, followed by its coating with gold to form SPIONs@Au, which further conjugated with luteinizing hormone-releasing hormone (LHRH) protein by making use of the cysteamine (Cyst) space linker and finally loaded with 5-Fluororacil (5-Fu) anticancer drug to form SPIONs@Au-Cyst-LHRH_5-Fu composite. Thus formed composite was thoroughly characterized by making use of the instrumental analysis such as HRTEM, EDAX, DLS, TGA, XPS, UV-vis, FTIR, HPLC and SQUID magnetics. We found from the analysis that the particles are spherical in shape, monodispersed with a size distribution of around 6.9nm in powdered dry form, while in solution phase it is 8.7nm. The UV-vis, FTIR, and HPLC studies confirmed for the loading of the 5-Fu drug onto the surface of SPIONs core and the maximum amount of drug that got adsorbed to be about 42%. The SQUID magnetic studies provided the information for the superparamagnetic behavior of the drug loaded SPIONs and the saturation magnetization (Ms) values observed to be about 11emu/g and the blocking temperature (T) of 348K. On testing the particles to see the effects of magnetic fluid hyperthermia (MFH) due to some changes in the solvent medium and oscillating frequency, the material seems to be highly active in aqueous medium and the activity gets increased with respect to the applied frequency of oscillation (430Hz>230Hz>44Hz). From the heat release studies, the calculated specific power loss (SPL) values for the SPIONs@Au-Cyst-LHRH_5-Fu composite are at the highest of 1068W/g in water (430Hz) vs the least of 68W/g in toluene (44Hz). Further, the drug release studies tested under the influence of magnetic field provided the information that the composite released its entire loaded drug following an exposure to the magnetic field (430Hz over 4h time), while only 53% (over 5h) for the controlled measurements of no magnetic field, thereby supporting to have the magnetic field so as to observe the externally controlled drug release effects. Finally, the results of the study provide the information that the SPIONs@Au-Cyst-LHRH_5-Fu composite can be potential for theranostic applications of cancer through the phenomenon of applying for MRI, magnetically controlled hyperthermia and drug delivery externally.
在此，我们开发了超顺磁性氧化铁纳米颗粒（SPIONs），使其分别适用于通过磁共振成像（MRI）进行癌细胞诊断以及通过磁控热疗/药物递送进行癌细胞治疗。为了制备复合材料，我们从SPIONs开始，接着用金对其进行包覆以形成SPIONs@Au，然后利用半胱胺（Cyst）间隔连接体使其与促黄体生成素释放激素（LHRH）蛋白共轭，最后负载5-氟尿嘧啶（5-Fu）抗癌药物以形成SPIONs@Au-Cyst-LHRH_5-Fu复合材料。通过诸如高分辨透射电子显微镜（HRTEM）、能量散射X射线光谱仪（EDAX）、动态光散射（DLS）、热重分析（TGA）、X射线光电子能谱（XPS）、紫外可见光谱（UV-vis）、傅里叶变换红外光谱（FTIR）、高效液相色谱（HPLC）和超导量子干涉仪磁学（SQUID magnetics）等仪器分析对如此形成的复合材料进行了全面表征。我们从分析中发现，颗粒呈球形，在干燥粉末形式下尺寸分布约为6.9nm，单分散，而在溶液相中为8.7nm。紫外可见光谱、傅里叶变换红外光谱和高效液相色谱研究证实了5-Fu药物负载在SPIONs核表面，吸附的最大药物量约为42%。超导量子干涉仪磁学研究提供了负载药物的SPIONs的超顺磁性行为信息，观察到的饱和磁化强度（Ms）值约为11emu/g，阻塞温度（T）为348K。在测试颗粒以观察由于溶剂介质和振荡频率的某些变化而产生的磁流体热疗（MFH）效果时，该材料在水性介质中似乎具有高活性，并且活性随着施加的振荡频率（430Hz>230Hz>44Hz）而增加。从热释放研究来看，SPIONs@Au-Cyst-LHRH_5-Fu复合材料在水中（430Hz）计算得到的比功率损耗（SPL）值最高为1068W/g，而在甲苯中（44Hz）最低为68W/g。此外，在磁场影响下进行的药物释放研究提供的信息表明，复合材料在暴露于磁场（430Hz，持续4小时）后释放了其全部负载的药物，而在无磁场的对照测量中仅释放了53%（持续5小时），从而支持了施加磁场以观察外部控制药物释放效果。最后，研究结果表明，通过应用MRI、磁控热疗和外部药物递送现象，SPIONs@Au-Cyst-LHRH_5-Fu复合材料在癌症的诊疗应用方面具有潜力。
