Well-Defined Macromolecule-Magnetic Nanoparticle Complexes

研究项目的智力价值。本研究的重点是嵌段共聚物的分子设计，其锚段有望与磁性金属或金属氧化物颗粒和尾块结合，以在水和有机载体介质中提供空间分散性。重点放在两个相互关联的要点上。其中包括具有疏水、玻璃状锚块和控制分子量尾部的共聚物分散剂的合成，研究它们作为胶束模板的功能，以生成控制尺寸的钴纳米颗粒，与粒径和共聚物结构/形态相关的分散特性，以及分析它们在提高磁性金属纳米颗粒耐久性方面的有效性。第二个重点是设计酶降解的磁铁矿分散剂，并研究磁性尺寸从10-100纳米增加到100纳米时的分散性。这些分散剂具有硅烷或硅氧烷锚，具有羧酸结合基团和选定的肽尾块。与通过碳二酰亚胺激活的氨基酸偶联或通过n -羧基氢化物开环制备的易聚合反应相比，多肽块包括本质上具有单模态分子量分布的模型。该研究的预期成果是制备尺寸可控的钴和磁性纳米颗粒的方法，并涂有大分子分散剂。所获得的有关共聚物结构和组成、粒度和分散性的知识将使配合物能够以磁性组分的最高体积分数制备。这将提供具有最高磁响应的分散性磁配合物。随着未来无机磁性组分的开发，也将为预测其他颗粒大分子组成物的性质提供坚实的基础。该计划的预期更广泛的方面：定制的大分子与磁性金属和金属氧化物纳米粒子的复合物可以为微电子和关键的生物医学技术“打开大门”。生物应用包括动脉内磁场定向药物定位的可能性，骨髓治疗的磁分离细胞靶向，通过交变磁场产生的热量治疗难以到达的恶性肿瘤的局部体内热疗，改进的诊断成像工具，以及视网膜脱离的治疗。量身定制的大分子分散剂的开发和理解是获得在必要的载体介质中保持分散性的配合物中磁性组分体积分数最大的材料的关键。也有可能：(1)合成这些纳米颗粒的反应介质的溶液结构可以用来控制原位生成的颗粒大小，(2)改进的聚合物涂层可以赋予生物相容性，(3)这些涂层可以提高颗粒抗氧化的耐久性。该项目将专注于培养研究生。在这种情况下，人们认识到今天的基础研究方法是多学科和全球性的。学生将通过在整个项目中就相互关联的研究重点进行合作，通过完成1学分的课程，提高所需的团队建设和沟通技巧。技术写作和口头交流课程，并通过每年参加科学会议来展示研究成果。他们将参加一个国际多学科工作组，通过电子方式分享想法，并为小组中的物理学家和药理学家准备研究的模型材料。通过这种方式，他们将获得与他们的材料相关的多学科研究成果，并将为物理学家和药理学家能够对定义良好的大分子和大分子磁性颗粒复合物进行仔细研究的研究基础设施做出贡献。

Intellectual Merit of the Research Program. This research focuses on the molecular design of block copolymers with anchor segments expected to bind to magnetic metal or metal oxide particles and tail blocks to provide steric dispersibility in aqueous and organic carrier media. Emphasis is devoted to two inter-related thrusts. One includes syntheses of copolymer dispersants with hydrophobic, glassy anchor blocks and controlled molecular weight tails, a study of their function as micellar templates for generating controlled-size cobalt nanoparticles, dispersive properties as related to particle size and copolymer structure/morphology, and anaylses of their effectiveness in improving durability of magnetic metal nanoparticles. The second thrust encompasses the design of enzymatically degradable dispersants for magnetite, and a study of dispersibility as related to magnetic size as it is increased from 10-100 nm in diameter. These dispersants have silane or siloxane anchors with carboxylate binding groups and selected peptide tail blocks. The polypeptide blocks include models with essentially uni-modal molecular weight distributions as compared to those prepared in facile polymerizations via carbodiimide-activated aminoacid coupling or by ring-opening of N-carboxyanhydrides. Anticipated outcomes of teh research are methodologies for preparing controlled size cobalt and magnetic nanoparticles, well-coated with macromolecular dispersants. The knowledge gained relating copolymer structure and composition, particle size, and dispersibility will enable complexes to be prepared with the highest possible volume fractions of the magnetic components. This will provide dispersible magnetic complexes with the highetst magnetic response. It will also provide a firm basis for predicting properties of other particle-macromolecular compositions as future inorganic magnetic components are developed. Anticipated Broader Aspects of the Program: Complexes of tailored macromolecules with magnetic metal and metal oxide nanoparticles could "open the door" to microelectronics and critical biomedical technologies. Biological applicatons include possibilities for intra-arterial, magnetic field-directed localization of drugs, cell targeting with magnetic separations for bone marrow treatments, localized in-vivo hyperthermia treatments for treating difficult-to-reach malignancies with heat generated via alternating magnetic fields, improved diagnostic imaging tools, and treatments for retinal detachments. The development and understanding of tailored macromolecular dispersants hold the key to obtaining materials with the maximum volume fraction of the magnetic component in the complexes that remain dispersible in the necessary carrier media. It is also probable (1) that the solution structures of the reaction media for synthesizing these nanoparticles can be used to control the in-situ generated particle size, (2) that improved polymer coatings can impart biocompatibility, and (3) that these coatings can improve particle durability against oxidation. The program will concentrate on educating graduate students. In this vein, it is recognized that today's fundamental research methods are multi-disciplinary and global. The students will enhance needed team-building and communication skills by collaborating throughout the program on inter-related research thrusts, by completing a 1-cr. course each in technical writing and in technical oral communication, and by annual participation in scientific meetings to present research findings. They will participate in an international multi-disciplinary working group by electronically sharing ideas, and by preparing model materials for study for physicists and pharmacologists in the group. In this way, they will derive multi-disciplinary research findings related to their materials and will also contribute to a research infrastructure whereby the physicists and pharmacologists will be able to conduct careful studies on well-defined macromolecules and macromolecular-magnetic particle complexes.