Surface Engineered Nanoparticles for MRI Contrast

描述(由申请人提供)： 这项研究的长期目标是开发一种用于癌症成像的多功能纳米颗粒造影剂，通过适当的表面工程，在单一包装中提供部位特异性以及诊断和治疗能力。将被研究的纳米颗粒材料是PI用于开发先进陶瓷和无机-有机杂化复合材料的材料。已经建立了对陶瓷纳米颗粒的元素组成进行表面工程的能力以及有效地控制颗粒表面的有机功能的能力。尚未确定的是工艺条件对它们用作造影剂的相关物理性质的影响，以及它们在动物模型中的行为。在没有努力优化成分的情况下，使用这些材料(R1&gt；30 mm(-1))S(-1)获得的初步结果清楚地证明，伽达尔材料证明了拟议的调查是合理的。此R21应用程序的目标是为基于纳米颗粒的系统的稳定性、弛豫度和颗粒大小的物理特性建立基准值，以用作磁共振成像(MRI)对比增强剂。基准性能将被用来确定纳米颗粒材料是否适合进一步研究。我们为这项R21研究工作组建的跨学科项目团队，SRI的物理科学、生物制药、政策部门和Alarion，Inc.将成为这一应用的分包商，他们拥有必要的能力和专业知识来执行材料合成和分析，以优化纳米颗粒造影剂的性能，进行毒理学和药代动力学分析，并开始试剂开发过程，如果此应用的结果得到保证。

DESCRIPTION (provided by applicant): The long-term goal of this research is to develop a multifunctional nanoparticulate contrast agent for cancer imaging that, through proper surface engineering, affords site specificity coupled with both diagnostic and therapeutic capabilities in a single package. The nanoparticulate material that will be investigated is one that the PI has employed in the development of advanced ceramics and inorganicorganic hybrid composites. The ability to surface engineer the elemental composition of the ceramic nanoparticle and the ability to effectively control the organic functionalities at the surface of the particulates have been established. What has not been established is the effect that process conditions have upon the physical properties relevant to their use as contrast agents, and their behavior in animal models. The preliminary results that have been obtained with these materials, r1 > 30 mM(-1)s(-1), with no effort to optimize the composition, clearly establishes that the GadAL materials warrant the proposed investigation. The goal of this R21 application is to establish benchmark values for the physical properties of a nanoparticle based system with respect to stability, relaxivity, and particle size for use as a magnetic resonance imaging (MRI) contrast enhancement agent. The benchmark properties will be used to determine if the nanoparticulate materials are suitable for further study. The interdisciplinary project team we have assembled for this R21 research effort, SRI's Physical Sciences, Biopharmaceutical, Policy Divisions and from Alerion, Inc., who will be a subcontractor on this application, have the capability and expertise necessary to perform the materials synthesis and analysis for optimization of the nanoparticulate contrast agent performance, conduct the toxicological and pharmacokinetics analysis, and begin the process of agent development should the results of this application warrant.