Engineering of Nanoparticles for Improved Outcome in Biomedical Applications

纳米颗粒工程可改善生物医学应用的结果

• 批准号: 418453-2012
• 负责人: Chithrani, Devika
• 金额: $ 1.6万
• 依托单位: Ryerson University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=531184
• 关键词: Engineering; Nanoparticles; Improved; Outcome; Biomedical

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.

放射疗法和化学疗法仍然是癌症治疗中最广泛使用的治疗选择，癌症研究的最新进展表明，将金纳米颗粒 (GNP) 纳入这些方案中可以增强肿瘤细胞的杀伤力。 GNP 被用作癌症治疗中的辐射剂量增强剂，也用作化疗中的抗癌药物载体。在这个研究项目中，GNP将用于优化放射疗法和化学疗法的联合治疗效果。 GNP 在这方面可以用作完美的模型系统，因为它们的尺寸、形状和表面特性可以轻松定制。例如，我之前的工作表明，纳米粒子的大小和形状在单层细胞水平的细胞摄取和运输过程中发挥着重要作用，并且我在该领域的出版物在不到五年的时间里就获得了超过 1,000 次引用。这也表明了进行此类基础研究的必要性。然而，在这个研究项目中，我们将首次超越单层水平进入多层细胞模型（组织类材料），以研究纳米粒子的行为和组合治疗反应作为尺寸、形状、表面特性的函数。 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颗粒尺寸、形状和表面特性的变化。接下来，我们将把抗癌药物涂覆在GNP上，然后研究单层和多层细胞模型中的联合治疗效果。了解纳米颗粒在组织样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桥梁。然而，基于 NP 的平台仍处于开发的初始阶段，在应用于临床之前，需要进行更多的基础研究，如本拨款申请中所提出的。拟议的项目将使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使学生能够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良好的团队合作者。