Magnetic/Plasmonic Nanoparticles for Cancer Theranostics

1066343 PI：Girshick 该项目涉及用于癌症诊断和治疗的多功能纳米粒子的合成和表征。这些纳米粒子包括多层：超顺磁性氧化铁核、二氧化硅层、金壳和聚乙二醇 (PEG) 涂层。磁核为磁共振成像提供增强的对比度，并能够通过交变磁场加热，通过高温破坏肿瘤。金壳有利于光学成像，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调节颗粒的光学性质。 PEG 涂层提供了生物相容性表面，可以通过靶向配体进一步进行生物功能化。这项研究的智力价值在于，如果成功，一些项目活动将代表突破性的成就。该项目涉及纳米颗粒合成和装载这些纳米颗粒的生物系统表征之间的相互作用。正在开发一种工艺，其中通过一系列气相工艺生产三层纳米颗粒，该工艺构成纳米颗粒制造装配线，其中每层的尺寸和成分都控制在纳米级公差范围内。在与这些合成研究的密切互动中，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，该项目将实现多项突破：通过一系列气相过程生产多层纳米颗粒的新方法；首次对细胞中金壳纳米颗粒摄取进行拉曼成像，避免使用分子标记；首次测量纳米颗粒生物系统中激光热量的产生，以将从亚细胞到组织尺度的光学和热方法关联起来；第一种将热量产生与每个细胞的纳米颗粒数量联系起来的方法，从而提出了一种确定细胞中纳米颗粒摄取的简单光学方法。该项目涉及的合作汇集了纳米颗粒合成和气溶胶途径加工方面的专业知识以及生物系统中传热和传质方面的专业知识。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有一天可能会成为癌症治疗的重大进步。更广泛地说，该项目将导致人们更好地了解纳米颗粒与生物系统的相互作用。纳米粒子制造装配线可以构成用于生产用于其他类型应用（例如能量转换）的多功能纳米粒子的原型。该项目涉及两名研究生，处于高度跨学科的环境中。 PI 在让女性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，并将在该项目中继续这样做。最后，PI 一直积极参与多项涉及 K-12 学生和更广泛公众的外展活动，而跨学科项目将丰富此类外展活动。

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.