Magnetic/Plasmonic Nanoparticles for Cancer Theranostics

1066343 PI：Girshick该项目关注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。磁性核为磁共振成像提供增强的对比度，并能够被交变磁场加热，通过高温破坏肿瘤。金壳有利于光学成像，并可通过近红外辐射加热，通过光热消融提供癌症治疗。二氧化硅层抑制聚集的磁性纳米粒子和介导的颗粒？的光学性质。PEG涂层提供生物相容性表面，其可以用靶向配体进一步生物官能化。这项研究的智力价值在于，若干项目活动如果成功，将代表开创性的成就。该项目涉及纳米粒子合成和生物系统的表征，其中这些纳米粒子加载的相互作用。正在开发一种方法，其中通过一系列气相方法生产三层纳米颗粒，所述气相方法构成纳米颗粒制造装配线，其中将每层的尺寸和组成控制为纳米级公差。在与这些合成研究的密切相互作用中，对这些纳米颗粒在生物组织中的摄取、性质和行为进行研究。如果成功，该项目将构成几个突破：一种通过一系列气相过程生产多层纳米颗粒的新方法;第一次对细胞中金壳纳米颗粒摄取的拉曼成像，避免使用分子标记;第一次测量载有纳米颗粒的生物系统中的激光热生成，以关联从亚细胞到组织的尺度上的光学和热方法;第一种方法将热量产生与每个细胞的纳米颗粒数量联系起来，从而提出了一种用于确定细胞中纳米颗粒摄取的简单光学方法。该项目涉及一项合作，将纳米颗粒合成和气溶胶路线处理方面的专业知识与生物系统中热量和质量传递方面的专业知识结合在一起。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，热和质量传输科学，光学和化学。该项目有几个更广泛的影响。该项目正在开发的工具可能有一天会成为癌症治疗的重大进展。更广泛地说，该项目将导致更好地理解纳米粒子与生物系统的相互作用。纳米颗粒生产装配线可以构成生产用于其他类型应用的多功能纳米颗粒的原型，例如在能量转换中。该项目涉及两名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其研究方面有着良好的记录，并将继续在该项目中这样做。最后，PI一直积极参与涉及K-12学生和更广泛公众的几个项目，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得到丰富。

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.