Novel Magnetic Nanoparticles for Biomedical Application

用于生物医学应用的新型磁性纳米粒子

• 批准号: 6727050
• 负责人: Galina Z. Goloverda
• 金额: $ 11.72万
• 依托单位: XAVIER UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6727050
• 关键词: X ray crystallography; acid base balance; biomaterial compatibility; biomaterial development /preparation; chemical synthesis; citrates; crystallization; fluidity; ligands; light scattering; magnetic resonance imaging; malates; metal oxide; metals; nanotechnology; phthalates; spectrometry; transmission electron microscopy

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.

该项目的长期目标是开发具有适合医学特性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磁性药物载体治疗致命疾病以及磁性标记或磁共振成像中的诊断工具。在生物医学应用中使用当前可用的材料的主要局限性是缺乏定义明确且特征良好的颗粒，这些颗粒在生物流体中具有化学稳定，具有较大的磁化易感性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。该项目着重于定义更好的发展和 在生理pH值下的人体液体中，磁性材料（例如Fe，Co，其氧化物和金属/氧化物复合材料）的纳米级颗粒（例如Fe，Co，其氧化物和金属/氧化物复合材料）将是无毒且稳定的。我们的策略是设计纳米级无机/有机复合材料，仅无机核决定了其磁性，而亲水有机壳可以控制其在水中的稳定性和溶解度。根据特定应用的要求，将制备不同大小和磁性行为的颗粒，并以透射电子显微镜，X射线衍射法和磁性测量为特征。我们将用来实现目标的技术是可控制的：磁芯的形成和生长及其随后的封装在亲水有机壳中，可以作为单独的步骤完成。新开发 长链多源性亲水性桥接配体将合成并测试其在生物流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：一个多态供体的头部，预先定制了与几个金属中心结合纳米颗粒表面上的几个金属（例如，母酸，柠檬酸或邻苯甲酸），长长的氢链（例如，氧化物）的替代（例如，多乙烯氧化物）在nanopictial consipation（例如，多乙烯氧化物）之间进行了良好的分离（例如，多乙烯氧化物）和/或药物分子（例如COOH，NH2）。在生理pH值下，在水溶液中获得的无机/有机复合纳米颗粒的溶解度，稳定性和动态行为将通过动态光学散射技术和分光光度计来研究。基于 结果，将通过改变取代基的长度以及引入中性（CH2OH）和离子（SO3-）组以及羧基和氨基末端来控制它们。