Novel Magnetic Nanoparticles for Biomedical Application

该项目的长期目标是开发具有合适性能的新型生物相容磁性纳米晶材料用于医学。潜在的应用包括用作磁性靶向药物载体，用于治疗致命疾病，以及用作磁性标记或磁共振成像的诊断工具。目前可用材料在生物医学应用中的一个主要限制是缺乏在生物流体中化学稳定、具有较大磁化率和低颗粒间相互作用的定义良好和表征良好的颗粒。同时完成这些任务是一项重大的研究挑战。该项目的重点是开发定义更好的 特性更好的磁性材料纳米颗粒(例如，铁、钴、其氧化物和金属/氧化物复合材料)，在生理pH值下在人体体液中无毒和稳定。我们的策略是设计一种纳米级的无机/有机复合材料，其中无机核单独决定其磁性，而亲水的有机壳层控制其在水中的稳定性和溶解性。根据特定应用的需要，将制备不同尺寸和磁性的颗粒，并用透射电子显微镜、X射线衍射仪和磁性测量对其进行表征。我们将用来实现我们的目标的技术是唯一可控的：磁芯的形成和生长以及随后将其封装到亲水有机外壳中可以作为单独的步骤完成。新开发的 将合成长链多齿亲水桥联配体，并测试其在生物体液中增溶和稳定纳米颗粒的能力。配体将以生物相容化合物为基础，由三个结构部分组成：预先排列的多齿给体头，用于结合到纳米粒子表面的几个金属中心(例如，苹果酸、柠檬酸或邻苯二甲酸)；长亲水链(例如，聚氧乙烷)，以确保纳米粒子核心之间的充分分离；以及末端官能团，用于结合生物和/或药物分子(例如，COOH，NH2)。利用动态光学散射技术和分光光度法研究得到的无机/有机复合纳米粒子在生理pH值条件下在水溶液中的溶解度、稳定性和动态行为。基于 结果通过改变取代基的长度以及引入中性基团(CH2OH)和离子基团(SO3-)以及羧基和氨基来控制它们。

The long-term goal of this project is to develop novel biocompatible magnetic nanocrystalline materials with suitable properties for use in medicine. Potential applications include their use as magnetic targeted drug carriers for treatment of lethal diseases and as diagnostic tools in magnetic labeling or magnetic resonance imaging. A major limitation to the use of currently available materials in biomedical applications is the lack of well-defined and well-characterized particles that are chemically stable in biological fluids, have large magnetic susceptibility, and low inter-particle interactions. Fulfillment of these tasks simultaneously represents a significant research challenge. This project focuses on the development of better-defined and better-characterized nanoscale particles of magnetic materials (e.g. Fe, Co, their oxides and metal/oxide composites) that would be non-toxic and stable in human fluids at physiological pH. Our strategy is to design a nanoscale inorganic/organic composite, where the inorganic core alone determines its magnetic properties, while the hydrophilic organic shell controls its stability and solubility in water. As required by a particular application, particles of different sizes and magnetic behavior will be prepared and characterized by transmission electron microscopy, X-ray diffractometry and magnetic measurements. The technique we will use to achieve our goal is uniquely controllable: the formation and growth of the magnetic core and its subsequent encapsulation into a hydrophilic organic shell can be done as separate steps. Newly developed long-chain polydentate hydrophilic bridging ligands will be synthesized and tested for their ability to solubilize and stabilize the nanoparticles in the biological fluids. The ligands will be based on biocompatible compounds and consist of three structural parts: a polydentate donor head prealigned for binding to several metal centers on a nanoparticle surface (e.g. malic, citric or phthalic acids), a long hydrophilic chain (e.g. polyethylene oxide) to assure sufficient separation between the nanoparticle cores, and a terminal functional group for binding biological and/or drug molecules (e.g. COOH, NH2). Solubility, stability and dynamic behavior of the obtained inorganic/organic composite nanoparticles in aqueous solution at physiological pH values will be studied by dynamic optical scattering techniques and spectrophotometry. Based on the results, they will be controlled by varying the length of the substituents and by introducing neutral (CH2OH) and ionic (SO3-) groups along with carboxy and amino termini.