Inorganic Nanoparticles in Non-Polymeric Organic Coating for Biomedical Applicati

用于生物医学应用的非聚合有机涂层中的无机纳米颗粒

• 批准号: 7895786
• 负责人: Galina Z. Goloverda
• 金额: $ 11.22万
• 依托单位: XAVIER UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895786
• 关键词: Acids; Address; Affect; Air; Aluminum Oxide; Area; Binding; Biocompatible; Biological; Biomedical Engineering; Carboxylic Acids; Cells; Chemistry; Collaborations; Colloids; Complement; Complex; Data; Development; Diffusion; Drug Delivery Systems; Epoxy Compounds; Ethylene Oxide; Fever; Goals; Grant; Hydrolysis; Hydroxyl Radical; In Vitro; Intention; Left; Ligands; Liquid substance; Magnetism; Marketing; Measurement; Measures; Medical; Metals; Methods; Minerals; Modeling; Molecular; Organic Synthesis; Oxides; Oxygen; Paper; Penetration; Performance; Pharmacologic Substance; Pharmacy facility; Polymers; Powder dose form; Predisposition; Preparation; Principal Investigator; Property; Publications; Reaction; Research; Science; Solutions; Spectrometry; Structure; Surface; Techniques; Thick; Tissues; Training; Work; X ray diffraction analysis; X-Ray Diffraction; adduct; aqueous; base; biocompatible polymer; cancer therapy; college; functional group; in vitro testing; interest; iron oxide; light scattering; magnetic field; magnetite ferrosoferric oxide; metal oxide; nanocomposite; nanocrystal; nanoparticle; novel; nucleophilic addition; oxidation; particle; programs; public health relevance; response; zeta potential

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.

描述（由申请人提供）：磁性纳米粒子作为药物输送、热疗和细胞追踪剂的性能取决于它们在生物介质中的磁化率、移动性和扩散特性。目前市场上的大多数功能性纳米颗粒都采用生物相容性聚合物来包裹这些颗粒，从而稳定其胶体。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期望响应。此外，聚合物壳使纳米复合材料变大，从而限制了其流动性和渗透性能。拟议的项目解决了这个问题。该项目的最终目标是开发新的合成方法来制备具有优异性能的非聚合物配体封端的无机纳米粒子，用于生物医学应用。为了实现这一目标，现提出以下计划。我们将首先研究多齿1-羟基羧酸与金属氧化物纳米晶体表面的配位，以了解无机-有机界面的结构如何影响纳米颗粒的胶体性质。我们将使用其分子几何形状可能会促进其以桥接模式配位的酸，同时使一个或多个活性基团未结合。然后，为了用生物相容性有机壳的保护层覆盖纳米颗粒，我们计划利用酸的未结合官能团直接在酸封端纳米颗粒的表面上进行有机合成。胶体氧化铝将与超顺磁性氧化铁一起用于有机配体合成的开发，这将减少不需要的氧化的可能性，并且还允许使用 NMR 进行产品分析。假设为氧化铝开发的有机合成技术也适用于氧化铁。或者，使用强酸或强碱分解氧化铝-有机纳米复合材料，并且分离的游离配体将与不含配体的氧化铁纳米颗粒反应以组装磁性无机核-有机壳纳米复合材料。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研究。动态光散射和电泳方法将用于测量流体动力学尺寸和 zeta 电位。形成最稳定的胶体并具有最强磁响应的纳米复合材料将被送往体外测试。 公共健康相关性：该项目旨在开发具有卓越特性的新型磁性输送剂，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体液的相容性，这些无聚合物载体的表面将通过直接在纳米颗粒表面上的有机合成进行化学修饰。该项目将开发这种有机合成。