Engineering of Nanoparticles for Improved Outcome in Biomedical Applications

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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.