Magnetic/Plasmonic Nanoparticles for Cancer Theranostics

本项目涉及用于癌症诊断和治疗的多功能纳米颗粒的合成和表征。这些纳米颗粒包括几层：超顺磁性氧化铁核、二氧化硅层、金壳和聚乙二醇（PEG）涂层。磁芯为磁共振成像提供了增强的对比度和被交变磁场加热的能力，通过高热破坏肿瘤。金外壳有利于光学成像，并且可以通过近红外辐射加热，通过光热消融提供癌症治疗。二氧化硅层抑制磁性纳米颗粒的聚集并介导颗粒的形成。S光学性质。PEG涂层提供了一种生物相容性表面，可以通过靶向配体进一步实现生物功能化。这项研究的智力价值在于，几个项目活动如果成功，将代表突破性的成就。该项目涉及纳米颗粒合成和这些纳米颗粒装载的生物系统表征的相互作用。目前正在开发一种工艺，通过一系列气相工艺生产三层纳米颗粒，这些工艺构成了一条纳米颗粒制造装配线，其中每层的尺寸和组成都被控制在纳米级公差范围内。在这些合成研究的密切配合下，研究人员对这些纳米颗粒在生物组织中的吸收、性质和行为进行了研究。如果成功，该项目将构成几个突破：通过一系列气相工艺生产多层纳米颗粒的新方法；避免使用分子标记的第一个细胞内金壳纳米颗粒摄取的拉曼成像；首次测量纳米颗粒负载生物系统中的激光热产生，以关联从亚细胞到组织的尺度上的光学和热方法；这是第一种将热量产生与每个细胞中纳米颗粒的数量联系起来的方法，从而提出了一种简单的光学方法来确定细胞中纳米颗粒的摄取。该项目涉及一项合作，将纳米颗粒合成和气溶胶途径加工方面的专业知识与生物系统传热传质方面的专业知识结合起来。这项工作是高度跨学科的，涉及颗粒和多相过程，纳米制造，生物工程，生物材料，热学和质量传输科学，光学和化学。该项目有几个更广泛的影响。这个项目正在开发的工具可能有一天会在癌症治疗方面取得重大进展。更广泛地说，这个项目将导致对纳米粒子与生物系统的相互作用有更深入的了解。纳米粒子制造装配线可以构成为其他类型应用（例如能量转换）生产多功能纳米粒子的原型。这个项目涉及两个研究生在一个高度跨学科的环境。pi在让妇女和其他代表性不足的群体以及本科生参与研究方面有着良好的记录，并且在本项目中继续这样做。最后，pi积极参与了几个项目，包括向K-12学生和更广泛的公众推广，以及更广泛的公众，这种类型的推广活动将通过跨学科项目而丰富。

1066343 PI: Girshick This project is concerned with the synthesis and characterization of multifunctional nanoparticles for cancer diagnosis and therapy. These nanoparticles include several layers: a superparamagnetic iron oxide core, a silica layer, a gold shell, and a coating of polyethylene glycol (PEG).The magnetic core provides enhanced contrast for magnetic resonance imaging and the ability to be heated by alternating magnetic fields, destroying tumors by hyperthemia. The gold shell facilitates optical imaging, and can be heated by near infrared radiation, providing cancer therapy by photothermal ablation. The silica layer suppresses aggregation of the magnetic nanoparticles and mediates the particle?s optical properties. The PEG coating provides a biocompatible surface that can be further biofunctionalized with targeting ligands. The intellectual merit of this research lies in the fact that several project activities will, if successful, represent groundbreaking accomplishments. The project involves an interplay of nanoparticle synthesis and characterization of biological systems in which these nanoparticles are loaded. A process is being developed in which three-layer nanoparticles are produced by a sequence of vapor-phase processes that constitute a nanoparticle manufacturing assembly line in which the dimensions and composition of each layer are controlled to nanoscale tolerances. In close interaction with these synthesis studies, studies are conducted of the uptake, properties and behavior of these nanoparticles in biological tissue. If successful the project will constitute several breakthroughs: a new methodology for production of multilayer nanoparticles by a sequence of gas-phase processes; the first Raman imaging of gold-shell nanoparticle uptake in cells that avoids the use of molecular labels; the first measurement of laser heat generation in nanoparticle-laden biological systems to correlate optical and thermal approaches at scales ranging from sub-cellular to tissue; the first method to link heat generation to the number of nanoparticles per cell, thereby suggesting a simple optical method for determining nanoparticle uptake in cells. The project involves a collaboration that brings together expertise in nanoparticle synthesis and processing by aerosol routes with expertise in heat and mass transfer in biological systems. This work is highly interdisciplinary, involving particulate and multiphase processes, nanomanufacturing, bioengineering, biomaterials, thermal and mass transport sciences, optics and chemistry. The project has several broader impacts. This project is developing tools that may one day constitute a major advance in the treatment of cancer. More broadly, this project will lead to greater understanding of the interactions of nanoparticles with biological systems. The nanoparticle manufacturing assembly line could constitute a prototype for producing multifunctional nanoparticles for other types of applications, for example in energy conversion. This project involves two graduate students in a highly interdisciplinary environment. The PIs have a strong record of involving women and other under-represented groups, as well as undergraduates, in their research, and are continuing to do so in this project. Finally, the PIs have been active in several programs involving outreach to K-12 students and the broader public, and the broader public, and outreach activities of this type will be enriched by the interdisciplinary project.