Engineering of Nanoparticles for Improved Outcome in Biomedical Applications

放射治疗和化疗仍然是癌症治疗中使用最广泛的治疗方案，癌症研究的最新进展表明，将金纳米颗粒(GNPs)掺入这些方案中可以增强对肿瘤细胞的杀伤力。GNP在癌症治疗中被用作辐射剂量增强剂，在化疗中也被用作抗癌药物载体。在这项研究项目中，GNPs将被用于优化放射治疗和化疗的联合治疗效果。在这方面，GNP可以作为一种完美的模型系统，因为它们的大小、形状和表面属性可以很容易地定制。例如，我以前的工作表明，纳米粒子的大小和形状在其单层细胞水平的细胞摄取和运输过程中发挥着重要作用，我在这一领域的出版物在不到五年的时间里被引用了1000多篇。这也表明了进行此类基础性研究的必要性。然而，在这个研究计划中，我们将首次超越单层水平进入多层细胞模型(类组织材料)来研究纳米粒子的行为和联合治疗反应随其大小、形状和表面属性的函数。首先，我们将研究单层和多层细胞模型中辐射剂量增强效应随纳米粒子尺寸、形状和表面性质的变化。接下来，我们将把抗癌药物包覆在GNPs上，然后在单层和多层细胞模型中研究它们的联合治疗效果。了解NPs在组织状多细胞模型中的行为和联合治疗反应将更快地在研究和临床之间架起一座桥梁。然而，基于NP的平台仍处于发展的初级阶段，在能够应用于临床之前，还需要进行更多的基础研究，如本次拨款申请所建议的那样。拟议的项目将允许学生学习许多与纳米技术和生物学相关的技术。这种类型的多学科研究还将允许学生在更具协作性的工作环境中进行培训。这些学生将在未来的合作研究中成为很好的团队合作伙伴。

Radiation therapy and chemotherapy remain the most widely used treatment options in cancer treatment and recent developments in cancer research show that the incorporation of gold nanoparticles (GNPs) into those protocols has enhanced tumor cell killing. GNPs are being used as a radiation dose enhancer in cancer therapy and also as an anticancer drug carrier in chemotherapy. In this research project, GNPs will be used to optimize the combined therapeutic effects of radiation therapy and chemotherapy. GNPs can be used as a perfect model system in this regard since their size, shape and surface properties can be tailored easily. For example, my previous work shows that size and shape of NPs play a big role in their cellular uptake and transport process at monolayer cell level and my publications in this field have received over 1,000 citations in less than five years. This shows the need for such fundamental studies as well. However, in this research program, we will go beyond monolayer level into multilayer cell models (tissue like materials) for the first time to study the behavior and combined therapeutic response as a function of size, shape, surface properties of NPs. First, we will investigate the variation of radiation dose enhancement effects in monolayer and multilayer cell models as a function of size, shape and surface properties of NPs. Next, we will coat anticancer drugs onto GNPs and then investigate the combined therapeutic effects in monolayer and multilayer cell models. Understanding of the behavior and combined therapeutic response of NPs in tissue-like multicellular models will bridge the interface between research and clinic sooner. However, NP-based platforms are still at the initial stage of development and much more fundemental studies is required as proposed in this grant application before they can be applied in the clinic. The proposed project will allow students to learn many techniques related to nanotechnology and biology. This type of multidisciplinary research will also allow students to train in a more collaborative working environment. These students will become good team players in the future collaborative research.