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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=551424
• 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.

放射治疗和化疗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，在这些方案中加入金纳米粒子（GNPs）增强了肿瘤细胞的杀伤作用。GNPs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。在本研究项目中，GNPs将用于优化放疗和化疗的联合治疗效果。GNPs在这方面可以作为一个完美的模型系统，因为它们的大小、形状和表面性质可以很容易地定制。例如，我之前的工作表明，在单层细胞水平上，NPs的大小和形状在细胞摄取和运输过程中起着重要作用，我在该领域的出版物在不到五年的时间里被引用了1000多次。这也表明需要进行这样的基础研究。然而，在本研究项目中，我们将首次超越单层水平进入多层细胞模型（组织样材料），研究NPs的大小，形状，表面特性的行为和综合治疗反应。首先，我们将研究辐射剂量增强效应在单层和多层细胞模型中随NPs大小、形状和表面性质的变化。接下来，我们将在GNPs上涂覆抗癌药物，然后在单层和多层细胞模型上研究联合治疗效果。了解NPs在组织样多细胞模型中的行为和联合治疗反应将更快地连接研究和临床之间的接口。然而，基于np的平台仍处于发展的初始阶段，在应用于临床之前，需要进行更多的基础研究。该计划将让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也将使学生在一个更协作的工作环境中训练。这些学生将在未来的合作研究中成为优秀的团队成员。