RUI: Development of Multifunctional Fluorine MRI Contrast Agents Based on Porous Silica Nanoparticles
RUI:基于多孔二氧化硅纳米粒子的多功能氟MRI造影剂的开发
基本信息
- 批准号:1410387
- 负责人:
- 金额:$ 13.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-01 至 2018-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Non-Technical:This award by the Biomaterials Program in the Division of Materials Research to Canisius College is to develop novel fluorine-containing MRI contrast agents based on the use of porous silica nanoparticles. The toxicity of many drugs limits the amount of drug that can be administered, especially for many chemotherapies used to treat cancer. Drug-delivery agents are materials that encapsulate drugs and protect healthy tissue from these potentially negative side-effects. Most drug-delivery agents include modifications that allow the drug-delivery agent, and therefore the drug, to accumulate preferentially at only the diseased tissue, allowing an even greater local dose at the target. State-of-the-art drug-delivery agents also contain imaging agents, such as a dye or contrast agent, that allows for the simultaneous pinpointing of diseased tissue and delivery to it. One imaging agent that has seen minimal use in combined drug-delivery applications is fluorine magnetic resonance imaging (MRI), due to limitations in the delivery vehicle. This project aims to create a new class of multifunctional fluorine MRI contrast agents based on a well known drug-delivery system, porous silica nanoparticles. These materials are like microscopic sponges (made out of the same material as sand) that can be modified with the fluorine agent while simultaneously being loaded with a drug, creating a combined drug-delivery and imaging agent. This research will predominantly be carried out by undergraduate researchers at Canisius College, providing an important training opportunity for young chemists. In addition, this research will also enable collaborations with the nearby Roswell Park Cancer Institute and SUNY University at Buffalo. Finally, this project will impact the broader Buffalo community because of the creation and integration of an activity involving nanoscience with the Summer Science Camp at Canisius College, enhancing STEM education in the region.Technical:Targeted drug-delivery using multifunctional particles, combining choice of therapeutic payload, molecular targeting, biocompatibility, and an imaging agent, has become a major research focus as a means to overcome the limitations of low therapeutic efficacy and toxicity caused by systemic administration of chemotherapeutic drugs for treating cancer. There is currently no drug-delivery agent incorporating a fluorine magnetic resonance imaging (MRI) contrast agent that provides all of these characteristics. The objective of this project is to synthesize fluorine MRI contrast agents based on silica nanoparticles and to identify the factors that maximize the fluorine MR signal using this platform. The PI hypothesizes that fluorine atoms immobilized to porous silica particles using linkers that maximize hydration either through charged groups or short hydrophilic polymers will have sufficient molecular flexibility in aqueous systems to be observable by MRI. If successful, these materials will, for the first time, combine the advantages of porous silica nanoparticles with those of fluorine MRI. This project will support undergraduate researchers who will prepare the materials via organic and inorganic synthesis, providing an important training opportunity for young chemists. These students will also use modern equipment to fully characterize the materials, including electron microscopy and fluorine MR imaging at extramural locations, further enhancing the educational impact. Finally, this project will impact the broader Buffalo community because of the creation and integration of an activity involving nanoscience (colloidal gold nanoparticles) with the Summer Science Camp at Canisius College.
非技术性:Canisius学院材料研究部生物材料项目的这一奖项旨在开发基于多孔二氧化硅纳米颗粒使用的新型含氟MRI造影剂。 许多药物的毒性限制了可以施用的药物的量,特别是对于用于治疗癌症的许多化学疗法。药物递送剂是封装药物并保护健康组织免受这些潜在负面副作用的材料。大多数药物递送剂包括允许药物递送剂以及因此药物优先仅在患病组织处积聚的修饰,从而允许在靶处的甚至更大的局部剂量。最先进的药物递送剂还含有成像剂,如染料或造影剂,其允许同时精确定位患病组织并递送至其。由于递送载体的限制,在组合药物递送应用中使用最少的一种成像剂是氟磁共振成像(MRI)。该项目旨在基于众所周知的药物递送系统,多孔二氧化硅纳米颗粒,创建一类新的多功能氟MRI造影剂。这些材料就像显微镜下的海绵(由与沙子相同的材料制成),可以用氟试剂进行修饰,同时装载药物,从而产生组合的药物递送和成像剂。这项研究将主要由Canisius学院的本科研究人员进行,为年轻化学家提供重要的培训机会。此外,这项研究还将与附近的罗斯韦尔公园癌症研究所和纽约州立大学布法罗分校合作。最后,该项目将影响更广泛的布法罗社区,因为创建和整合的活动涉及纳米科学与暑期科学营在卡尼修斯学院,加强STEM教育在region.Technical:有针对性的药物输送使用多功能粒子,结合选择的治疗有效载荷,分子靶向,生物相容性,和成像剂,已成为一个主要的研究重点,作为一种手段,以克服低治疗效果和毒性所造成的局限性全身化疗药物治疗癌症。目前还没有包含氟磁共振成像(MRI)造影剂的药物递送剂提供所有这些特征。本项目的目标是合成基于二氧化硅纳米颗粒的氟MRI造影剂,并确定使用该平台使氟MR信号最大化的因素。PI假设,使用通过带电基团或短亲水聚合物最大化水合的连接体固定到多孔二氧化硅颗粒上的氟原子在水性系统中具有足够的分子柔性,可通过MRI观察到。如果成功的话,这些材料将首次将多孔二氧化硅纳米颗粒的优点与氟MRI的优点联合收割机结合起来。该项目将支持通过有机和无机合成制备材料的本科研究人员,为年轻化学家提供重要的培训机会。这些学生还将使用现代设备来充分表征材料,包括电子显微镜和氟MR成像在校外的位置,进一步提高教育的影响。最后,这个项目将影响更广泛的布法罗社区,因为创建和整合的活动涉及纳米科学(胶体金纳米粒子)与卡尼修斯学院的暑期科学营。
项目成果
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