Date of Award
December 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Julia Zhao
Second Advisor
Diane Darland
Abstract
Nanomaterials have emerged as a pivotal area of research in chemistry, driven by their unique properties that make them suitable for both industrial and biomedical applications. Among nanomaterials, nanozyme is a series of nanomaterials with enzyme-mimetic activities that can proceed with the catalytic reactions of natural enzymes, conferring significant potential for their use in various biomedical applications. Herein, we describe three types of nanomaterials products with distinct properties and applications: 1) Fe³⁺-doped graphene quantum dots (GQDs) for sensitive H₂O₂ detection; 2) ratiometric fluorescent nanoprobes based on near-infrared (NIR) semiconducting polymer dots for label-free detection of dopamine; and 3) Multifunctional near Infrared polymer pots for enhanced synergistic photodynamic/photothermal therapy.In this dissertation, the first chapter is a comprehensive review of nanozymes and their biotargets, including the challenges with natural enzymes and the rapid development of nanozymes, their synthetic counterparts. This chapter highlights the different types of nanozymes and their functional groups, including metal or metal oxide-based nanozymes, metal-organic frameworks (MOFs), and carbon-based nanomaterials. I further explore and compare the reaction mechanisms of nanozymes, such as peroxidase, oxidase, and superoxide dismutase-like activities. I also provide my perspective on current and future applications for biosensing from ions, small molecules, nucleic acids, and proteins to cancer cell detection. The chapter was finished with current challenges in the field, suggesting future research directions to address impediments to nanozyme synthesis and application.
The second chapter details the development of sensitive fluorescence-based GQDs, synthesized using polyethyleneimine (PEI) as a precursor, doped with Fe³⁺ via a “bottom-up” method. The Fe³⁺ in the GQDs facilitated catalase-like activity by catalyzing H₂O₂ through a complex Fenton reaction. The synthesized GQDs-Fe exhibited a high quantum yield (67%) and rapid sensitivity to H₂O₂ in neutral pH, with a low limit of detection (LOD) of 20 nM, achieved within seconds. These features are a marked improvement compared with current methods.In the third chapter, ratiometric fluorescent nanoprobes based on NIR semiconducting Pdots were prepared by blending two semiconducting polymers: poly[(9,9-dioctyl-2,7-divinylenefluorenylene)-alt-(2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene)] (PFPV) and Poly [2,1,3-benzothiadiazole-4,7-diyl-2,5-thiophenediyl(9,9-dioctyl-9H-9-silafluorene-2,7-diyl)-2,5-thiophenediyl] (PSiF-DBT), combined with an amphiphilic polymer Poly(Styrene-Co-maleic anhydride) cumene terminated (PSMA). The strong NIR fluorescence exhibited was due to the efficient Förster resonance energy transfer (FRET) from PFPV to PSiF-DBT. Dopamine quenched the NIR fluorescence through photo-induced electron transfer (PET) process with an LOD of 70 nM when 1 mg/L of Pdots reacted with dopamine for 20 minutes in HEPES buffer (pH = 8) with specificity compared to other common cellular molecules and neutransmitters. The fourth chapter describes the synthesis of multifunctional NIR Pdots using poly (styrene-co-maleic anhydride) (PSMA) as a crosslinker and backbone to form a compact core. Poly [2,6-(4,4-bis (2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-b′] dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) was employed as both an NIR photosensitizer and thermal agent, while Mn²⁺ ions were incorporated to produce O₂ through H₂O₂ catalysis, thereby achieving a photothermal conversion efficiency of 53%, a singlet oxygen (¹O₂) quantum yield of 46%, and enhanced ¹O₂ quantum yield up to 64 % with 10 µM H₂O₂. The synergistic photodynamic and photothermal therapeutic effects were tested in MCF7 human adenocarcinoma cells, with results assessed via cell viability assays and confocal imaging under laser irradiation achieving a combination index of 0.25 at effective does (ED) 50, while Pdots showed non-cytotoxic properties without laser irradiation. The fifth chapter summarizes the three research projects, detailing the limitations of nanozymes for biosensing, ratiometric fluorescence nanoprobes for biosensing, and Pdots for cancer therapy. Future strategies to enhance the performance of these nanomaterials are discussed, including improving biocompatibility, targeting specificity, overcoming biological barriers, developing multifunctional nanomaterials, and ensuring sustainable design. Addressing these challenges is essential to solidifying the role of nanomaterials in advancing medical diagnostics and treatment. This dissertation will demonstrate the efficacy of nanoparticles as nanozymes in sensitive detection of H₂O₂ and dopamine, as well as their potential to enhance clinical applications of photodynamic/photothermal therapy for cancer treatment. The anticipated outcomes include the successful development of highly sensitive, fluorescent and specific nanoprobes for biomedical applications, and the establishment of multifunctional Pdots as potential agents in cancer therapy. These findings could significantly contribute to clinical interventions, making early disease diagnosis more accurate and improving the efficacy of late-stage cancer treatments.
Recommended Citation
Wu, Yingfen, "Development, Characterization, And Application Of Nanomaterials For Target Detection And Therapeutic Study" (2024). Theses and Dissertations. 6583.
https://commons.und.edu/theses/6583