Year

2022

Degree Name

Doctor of Philosophy

Department

Institute for Superconducting and Electronic Materials

Abstract

Cancer is one of leading cause of human mortality across the world, both in developed and developing countries. Cancer is a complex disease due to its multifacets and multifactor nature. Recently, various studies on cancer revealed that the redox imbalance is one of underlying factor for cancer development and progression. The imbalance in redox homeostasis is mainly caused by overproduction of free radicals, predominately by reactive oxygen species (ROS). ROS can be generated from extrinsic (chemicals, pollutants, radiations, and certain drugs) or intrinsic (mitochondrion, inflammation or enzymatic components). These free radicals cause oxidative stress and leads to damage of biomolecules and tissues. Higher level of ROS and dysregulation of antioxidant system result in malignant transformation and progression through biomolecules attack.

To support the underperforming antioxidant system and suppress the overproduction of ROS, different types of antioxidant or ROS scavenging materials are employed. These materials can be organic or inorganic and function by slowing down or preventing the autoxidation of oxidizable molecules. Inorganic nanoparticles (NPs) offers great advantages over organic NPs due to their excellent diagnostic and therapeutic properties. As compared to organic nanoparticles, inorganic NPs offers higher selectivity in drug delivery, higher drug loading capability, stability in the biological environment, higher surface area, higher photostability, longer life-cycle and improved bioavailability. Combining the properties into one entity or nanosystem is very advantageous regarding to reduce the side effects of multicomponents or multidrugs. A single nanoplatform can offer multifunctional (diagnostic and therapeutic) characteristics with higher efficiency and biocompatibility.

Malignant cells usually generate and adopt to higher level of ROS and oxidative stress for their survival and progression. Nanostructures with controlled surface properties can be synthesized for selective generation and scavenging of ROS. ROS generation and scavenging depend upon various factors such as pH of microenvironment, morphology and oxidation state of elements in the nanostructure, retention and selective behaviour of components. An increased ROS level can enhance oxidative stress beyond threshold limit and can cause oxidative burst. An oxidative burst in malignant cells can be an effective tool to kill cancer cells. Various nanostructures based Au, Ag, Mn, Mg Ce, Se, Fe, Ti, Zn, In, Bi, Ta, redox polymer and polyphenols cab be selectively employed in ROS scavenging or generation. The properties of metal oxide NPs can be altered by modification through oxygen surface deficiency or polymer binding or coating. Processing the nanostructures under controlled parameters such as inert atmosphere and chemical selection greatly affect the final properties of the structures. In this research, most potential oxide materials of La2O3, γ-Fe2O3, and CeO2 have been selected, and their nanostructures were synthesized for efficient diagnostic and therapeutic role in cancer treatment.

FoR codes (2008)

100709 Nanomedicine

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.