The effects of nanoparticle properties on biological imaging and photothermal cancer treatment

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Aioub, Mena
El-Sayed, Mostafa A.
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Over the past two decades, gold nanoparticles (AuNPs) have emerged as promising tools for biomedical applications. Their unique optical properties enable sensitive detection and effective treatment strategies. Additionally, the expanding toolkit of AuNP colloidal synthesis, combined with their straightforward surface functionalization, allowing for their conjugation with a variety of targeting and / or therapeutic ligands, contribute to their increasing use. This thesis explores the effects of nanoparticle size, shape, composition, and surface chemistry in the design and application of AuNPs for biological imaging and cancer treatment applications. The 1st chapter introduces various AuNP synthesis, characterization, and conjugation strategies, and presents an overview of their tunable optical properties. Recent AuNP applications such as biological imaging, diagnostics, and cancer treatments (Chapter 1) are reviewed to prepare the reader for the remaining chapters. Then, Chapter 2 discusses the effect of varying surface chemistries on nanoparticle localization within living cells. Using different targeting ligands, a dynamic profile of AuNP localization was obtained. Cellular localization was found to critically affect AuNP scattering properties, a crucial component of biological imaging. Increased subcellular targeting was found to result in greater and more rapid localization, resulting in increased light scattering and enhanced imaging (Chapter 2). Subsequently, the nuclear-targeted AuNPs (NT-AuNPs) previously found to give the greatest imaging enhancement were employed as probes to increase the inherent light scattering from cells. Chapter 3 describes a technique to use these NT-AuNPs to compare the relative efficacies of three clinically relevant chemotherapeutic drugs. This allows the use of a single sample of cells in real-time using inexpensive lab equipment, saving time and material costs while imparting the potential to rapidly screen drugs or analogs to determine the most effective option. The remainder of this thesis focuses on plasmonic photothermal therapy (PPT), an emerging treatment where AuNPs convert light into heat, causing cell death specifically in the vicinity of the targeted AuNPs. Chapter 4 discusses the use of NT-AuNPs to induce PPT cell death while simultaneously serving as scattering probes to monitor the associated molecular changes through time-dependent surface-enhanced Raman spectroscopy of single cells. The same molecular changes were observed using different AuNP sizes, concentrations, and laser intensities, indicating the consistency mechanism of action of PPT. Finally, the use of platinum-coated gold nanorods (PtAuNRs) is introduced in Chapter 5 to mitigate the side effects of PPT. Platinum, commonly used for oxygen reduction in catalysis, is incorporated to scavenge reactive oxygen species (ROS), allowing the decoupling of thermal and chemical effects during PPT. The PtAuNRs protected untreated cells from the ROS byproducts of PPT, making them ideal candidates to advance the treatment while reducing deleterious side effects. This thesis presents a fundamental investigation of the influence of AuNP properties on imaging and cancer treatment, which can be used to continue advancing their utility and applications.
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