Novel Magnetic Nanoparticles for Biomedical Application

该项目的长期目标是开发具有适合医学用途的新型生物相容性磁性纳米晶体材料。潜在的应用包括它们用作治疗致命疾病的磁性靶向药物载体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使用的一个主要限制是缺乏明确定义和良好表征的颗粒，这些颗粒在生物流体中化学稳定、具有大磁化率和低颗粒间相互作用。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更好定义和 具有更好特性的磁性材料纳米级颗粒（例如铁、钴、它们的氧化物和金属/氧化物复合材料），在生理 pH 值下在人体体液中无毒且稳定。我们的策略是设计一种纳米级无机/有机复合材料，其中无机核单独决定其磁性，而亲水性有机壳控制其稳定性和在水中的溶解度。根据特定应用的要求，将制备不同尺寸和磁性行为的颗粒，并通过透射电子显微镜、X射线衍射和磁性测量进行表征。我们用于实现目标的技术是独特可控的：磁芯的形成和生长以及随后封装到亲水有机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配体并测试其在生物液体中溶解和稳定纳米颗粒的能力。配体将基于生物相容性化合物，由三个结构部分组成：预先对准的多齿供体头，用于与纳米颗粒表面上的多个金属中心（例如苹果酸、柠檬酸或邻苯二甲酸）结合，长亲水链（例如聚环氧乙烷）以确保纳米颗粒核心之间的充分分离，以及用于结合生物和/或药物分子（例如COOH、NH2）的末端官能团。通过动态光散射技术和分光光度法研究所获得的无机/有机复合纳米粒子在生理pH值水溶液中的溶解度、稳定性和动态行为。基于 结果，它们可以通过改变取代基的长度以及通过引入中性（CH2OH）和离子（SO3-）基团以及羧基和氨基末端来控制。

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.