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，在单个包装中提供与诊断和治疗能力相结合的位点特异性。将被调查的纳米颗粒材料是一个PI已在先进的陶瓷和无机有机混合复合材料的发展。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和有效控制颗粒表面处的有机官能团的能力。尚未确定的是工艺条件对与其用作造影剂相关的物理性质及其在动物模型中的行为的影响。用这些材料获得的初步结果，r1 > 30 mM（-1）s（-1），没有努力优化组成，清楚地表明GadAL材料值得进行拟议的研究。该R21应用的目标是建立基于纳米颗粒的系统的物理性质的基准值，其关于稳定性、弛豫率和粒度，以用作磁共振成像（MRI）对比度增强剂。基准性能将用于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Alerion公司，其将作为本申请的分包商，具有进行材料合成和分析以优化纳米颗粒造影剂性能所需的能力和专业知识，进行毒理学和药代动力学分析，并开始试剂开发过程（如果本申请的结果得到保证）。

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.