Date of Degree
PhD (Doctor of Philosophy)
Salem, Aliasger K.
Larsen, Sarah C.
First Committee Member
Second Committee Member
Third Committee Member
Fourth Committee Member
Fifth Committee Member
The unique properties of nanomaterials, such as their small size and large surface area-to-volume ratios, have attracted tremendous interest in the scientific community over the last few decades. Thus, the synthesis and characterization of many different types of nanoparticles has been well defined and reported on in the literature. Current research efforts have redirected from the basic study of nanomaterial synthesis and their properties to more application-based studies where the development of functionally active materials is necessary. Today such nanoparticle-based systems exist for a range of biomedical applications including imaging, drug delivery and sensors. The inherent properties of the nanomaterial, although important, aren’t always ideal for specific applications. In order to optimize nanoparticles for biomedical applications it is often desirable to tune their surface properties. Researchers have shown that these surface properties (such as charge, hydrophobicity, or reactivity) play a direct role in the interactions between nanoparticles and biological systems can be altered by attaching molecules to the surface of nanoparticles.
In this work, the effects of physicochemical properties of a wide variety of nanoparticles was investigated using in vitro and in vivo models. For example, copper oxide (CuO) nanoparticles were of interest due to their instability in biological media. These nanoparticles undergo dissolution when in an aqueous environment and tend to aggregate. Therefore, the cytotoxicity of two sizes of CuO NPs was evaluated in cultured cells to develop a better understanding of how these propertied effect toxicity outcomes in biological systems. From these studies, it was determined that CuO NPs are cytotoxic to lung cells in a size-dependent manner and that dissolved copper ions contribute to the cytotoxicity however it is not solely responsible for cell death. Moreover, silica nanoparticles are one of the most commonly used nanomaterials because they are easy to synthesize and their properties (such as size, porosity and surface chemistry) can be fine-tuned. Silica nanoparticles can be found in thousands of commercially available products such as toothpastes, cosmetics and detergents and are currently being developed for biomedical applications such as drug delivery and biomedical imaging. Our findings herein indicate that the surface chemistry of silica nanoparticles can have an effect on lung inflammation after exposure. Specifically, amine-modified silica NPs are considered to be less toxic compared to bare silica nanoparticles. Together, these studies provide insight into the role that material properties have on toxicity and allow for a better understanding of their impact on human and environmental health.
The final aim of this thesis was to develop surface-modified nanoparticles for drug delivery applications. For this, biodegradable, polymeric NPs were used due to their inert nature and biocompatibility. Furthermore, polymeric NPs are excellent for loading drugs and using them as drug delivery vehicles. In this work, poly (lactic-co-glycolic acid) (PLGA) NPs were loaded with a therapeutic peptide. These NPs were then coated with chitosan (a mucoadhesive polymer) for the treatment of allergic asthma or coated with a small cationic mitochondrial targeting agent for the treatment of ischemia/reperfusion injury.
Taken as a whole, this thesis sheds light on the impact of NPs on human health. First by providing useful toxological data for CuO and silica NPs as well as highlighting the potential of surface-modified polymeric NPs to be used in drug delivery-based applications.
The unique properties of nanoparticles, such as their small size and large surface area-to- volume ratios, have attracted tremendous interest in the scientific community over the last few decades. A nanomaterial is defined as having one or more dimension in the nanometer (or 10-9 meters) size range. Although nanoparticles are already present in many consumer products such as toothpastes, cosmetics and sunscreens, it is not clear how exposure to nanoparticles will impact human and environmental health. Furthermore, there are conflicting and inconsistent toxicity profiles in the scientific literature for any given nanomaterial. Therefore, it is difficult to accurately assess the safety of nanoparticles upon human exposure. The first section of this thesis provides useful information concerning nanoparticle toxicity to the lungs. This work is important because inhalation is a major route of exposure for humans and it is necessary to understand the harm that nanoparticles can have on lung cells and tissue.
The second aim of this work was to use polymeric nanoparticles in a drug delivery-based application. Here, polymeric nanoparticles were used to encapsulate a drug. This is advantageous to protect the drug from degrading in the body and to target it to a specific tissue or organ. This nanoparticle-based system was found to be effective for preventing the onset of allergic asthma as well as for treating heart cells during injury.
Taken as a whole, this thesis addresses the impact of nanoparticles on human health by providing useful toxological data as well as highlighting the potential polymeric nanoparticles to be used in drug delivery-based applications.
Cell Culture, Nanoparticle, Toxicity
xix, 125 pages
Includes bibliographical references (pages 106-125).
Copyright © 2017 Angie Sue (Morris) Thorn
Thorn, Angie Sue (Morris). "The impact of nanoparticle surface chemistry on biological systems." PhD (Doctor of Philosophy) thesis, University of Iowa, 2017.