Inorganic Nanoparticles in Non-Polymeric Organic Coating for Biomedical Applicati

描述(申请人提供)：磁性纳米颗粒作为药物输送、热疗和细胞跟踪剂的性能取决于它们在生物介质中的磁化率、迁移率和扩散特性。今天市场上的大多数功能纳米颗粒都使用生物兼容聚合物包裹这些颗粒，从而稳定它们的胶体。由于聚合物随机附着在颗粒表面，因此它们必须很大，才能提供足够的稳定效果。因此，它们对核壳纳米复合材料的抗磁性贡献掩盖了其对外部磁场的预期响应。此外，聚合物壳使纳米复合材料变得很大，从而限制了其流动性和穿透性能。拟议的项目解决了这一问题。该项目的最终目标是开发新的合成方法，以制备具有优异性能的生物医学应用的非聚合物配体封端的无机纳米颗粒。为实现这一目标，现提出以下计划。我们将首先研究多齿1-羟基羧酸对金属氧化物纳米晶表面的配位作用，以了解无机-有机界面的结构如何影响纳米粒子的胶体性质。我们将使用其分子几何构型可能会以桥联模式促进其配位的酸，而不结合一个或多个活性基团。然后，为了在纳米颗粒上覆盖一层生物相容的有机外壳保护层，我们计划使用酸的非结合官能团直接在酸帽纳米颗粒的表面进行有机合成。胶体氧化铝将与超顺磁性氧化铁一起用于有机配体合成，这将减少不必要的氧化可能性，并允许使用核磁共振进行产物分析。这个假设是，为氧化铝开发的有机合成技术也将适用于氧化铁。或者，将氧化铝-有机纳米复合材料用强酸或强碱分解，并将分离的自由配体与无配体的氧化铁纳米颗粒反应，组装成磁性无机核-有机壳层纳米复合材料。将对组装的纳米复合材料在水溶液中的胶体稳定性和磁化率测量进行系统的研究。动态光散射法和电泳法将用于测量流体动力学尺寸和Zeta电位。形成最稳定胶体和具有最强磁响应的纳米复合材料将被送往体外测试。 与公共卫生相关：该项目旨在开发具有优异性能的新型磁性递送剂，用于靶向治疗受癌症影响的组织。为了确保稳定性和与生物流体的兼容性，这些无聚合物载体的表面将直接在纳米颗粒表面通过有机合成进行化学修饰。这种有机合成将在该项目中进行开发。

DESCRIPTION (provided by applicant): The performance of magnetic nanoparticles as drug delivery, hyperthermia and cell tracking agents depends on their magnetic susceptibility, mobility, and diffusion properties in biological media. Most of the functional nanoparticles on the market today utilize biocompatible polymers which wrap these particles and therefore stabilize their colloids. Since polymers attach to the particle surface randomly, they must be large in order to provide a sufficient stabilizing effect. As a consequence, their diamagnetic contribution to the core-shell nanocomposite obscures its desired response to an external magnetic field. In addition, polymeric shells make the nanocomposite large and thus limit its mobility and penetration properties. The proposed project addresses this problem. The ultimate goal of this project is to develop new synthetic methods for the preparation of non-polymeric- ligand-capped inorganic nanoparticles with superior properties for biomedical applications. The following plan is being proposed to achieve this goal. We will first study the coordination of polydentate 1-hydroxycarboxylic acids to the surfaces of metal oxide nanocrystals in order to gain an understanding of how the structure of the inorganic - organic interface affects the colloidal properties of the nanoparticles. We will use acids whose molecular geometry will likely promote their coordination in a bridging mode, while leaving one or more active groups unbound. Then in order to cover the nanoparticles with a protective layer of a biocompatible organic shell, we plan to perform organic synthesis directly on the surface of the acid-capped nanoparticles using the acid's unbound functional groups. Colloidal alumina will be used along with superparamagnetic iron oxides for the development of organic ligand synthesis which will decrease the possibility of undesired oxidation and also allow the use of NMR for the product analysis. The hypothesis is that organic synthesis techniques developed for alumina will work for iron oxides as well. Alternatively, the alumina-organic nanocomposites will be decomposed using a strong acid or base, and the isolated free ligands will be reacted with the ligand-free iron oxide nanoparticles to assemble the magnetic inorganic core-organic shell nanocomposites. A systematic study of the colloidal stability in aqueous solutions and the magnetic susceptibility measurements will be conducted for the assembled nanocomposites. Dynamic Light Scattering and electrophoretic methods will be used for measuring the hydrodynamic sizes and zeta potentials. The nanocomposites forming the most stable colloids and having the strongest magnetic response will be sent for in vitro testing. PUBLIC HEALTH RELEVANCE: The project aims at the development of novel magnetic delivery agents with superior properties for the targeted treatment of cancer-affected tissues. To assure stability and compatibility with biological fluids, the surface of these polymer-free carriers will be chemically modified by organic synthesis directly on the nanoparticle's surface. This organic synthesis will be developed in the project.