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|Title:||Engineering functional nanomaterials for photonic applications||Authors:||Chan, Kok Ken||Keywords:||Engineering::Electrical and electronic engineering||Issue Date:||2020||Publisher:||Nanyang Technological University||Source:||Chan, K. K. (2020). Engineering functional nanomaterials for photonic applications. Doctoral thesis, Nanyang Technological University, Singapore.||Abstract:||The tremendous progress in nanotechnology has provided diverse nanosized materials with unique and interesting features including but not limited to fluorescence, high sensitivity, high loading capacity, and photothermal properties which are beneficial for a wide range of photonic applications. Photons are employed in photonics to detect, transmit, transport, and process information that can achieve a tremendous enhancement in efficiency, capacity, simplicity, and speed. In view of these advantages, this thesis aims to perform in-depth studies of the synthesis and properties characterization that centered on three types of nanomaterial groups, including polymer, carbon, and perovskite-based nanoparticles. This work also exploits the respective unique features to showcase the potential of these nanoparticles in photonic applications. The work outlined in this thesis will be divided into three major photonic applications: i) cancer therapeutics, ii) single and multiphoton cellular imaging, and iii) sensing of trace level pollutants in food and water samples. Despite the remarkable advances made in understanding cancer biology and the development of new cancer therapies, cancer mortality is one of the rising mortalities causes throughout the world, and research has shown that this trend is expected to persist. In particular, pancreatic cancer is one of the deadliest with pancreatic cancer patients having a median survival rate of fewer than 6 months and the overall 5-year survival rate is less than 5%. Traditional pancreatic cancer treatments including, surgery, radiation, and chemotherapy, come with some adverse side effects such as low specificity, dose-limiting toxicity, poor pharmacokinetics, and insufficient uptake at the targeted site. Addressing these concerns, nanomaterial-based delivery systems stand as the alternative to overcome the limitations of traditional delivery of therapeutic agents. The employment of nanomaterials offers unparalleled options to introduce new functionalities for synergistic therapy, as well as to modulate fundamental properties such as solubility, drug-release behavior, blood circulation half-life, and immunogenicity. The nanoparticle-based delivery system can also provide a more effective administration route, reduce potential toxicity, offer protection towards therapeutic agents, encapsulate drugs with poor aqueous solubility, deliver therapeutic loads to targeted sites, and increase therapeutic efficiency, thus lowers dosage and frequency of administration. On the basis of the aforementioned facts, the first section in this thesis focus on developing biodegradable charged polyester-based vectors (BCPVs) for the co-delivery of K-ras and Notch1 siRNA to overcome drug resistance to gemcitabine (chemotherapeutic drug) in Mia PaCa-2, a pancreatic cancer cell line. K-ras regulates many downstream single molecules such as Raf kinase, Raf guanine, and nucleotide exchange factors that regulate cell growth, differentiation, and survival. Mutated K-ras gene at codon 12 keeps the constitutive GTPase activity and locks the protein to the guanosine triphosphate-bound “on” state, resulting in the cells having tumor phenotype and eventually evolve into cancer. On the other hand, overexpression of Notch1 resulted in the acquisition of epithelia-mesenchymal transition (EMT) phenotype by pancreatic cancer cells. EMT is often linked with resistance to chemotherapeutic drugs, thus lowering the therapeutic efficacy of chemotherapeutic agents. Hence, the silencing of both K-ras and Notch1 is a promising strategy since both genes are significant contributors to pancreatic tumorigenesis. BCPVs which are based on cationic polylactide has shown great potential as a delivery vehicle due to its low toxicity, biodegradability and biocompatible. In this work, BCPVs was used as a delivery vehicle for the co-delivery of K-ras and Notch1 siRNA to silence the multiple gene mutations in pancreatic cancer cells and to reduce drug resistance to gemcitabine. After treatment, the cell migration, proliferation and invasion were clearly inhibited, and the cell apoptosis was evidently increased by the synergistic therapeutic effect of the nanocomplex. The combinational RNAi therapy was also found to be able to improve the sensitivity of the Mia PaCa-2 cells towards gemcitabine. In the following chapter, graphene quantum dots (GQDs) were synthesized, characterized, and employed as a light-triggered fluorescent nanocarrier for co-delivery of K-ras siRNA and Doxorubicin (DOX) for combinational gene and chemotherapy for pancreatic cancer treatment. GQDs was employed as a nanocarrier due to its facile synthesis approach, low toxicity, biocompatible, and unique optical properties. DOX is an anthracycline antibiotic that has been found to be highly effective in killing cancer cells in both solid and liquid tumors by binding to DNA-associated topoisomerase enzymes II. To achieve a nanocomplex capable of performing combinational therapy, a GQD/DOX/BCPV/siRNA nanocomplex consists of DOX and siRNA with the assistance of BCPVs to modify the surface properties of GQDs for the co-loading of DOX and siRNA through electrostatic interaction. The formation of the nanocomplexes was carefully optimized to ensure the optimal loading of the therapeutic agents. The delivery and therapeutic efficiency of the GQD/DOX/BCPV/siRNA were evaluated in MiaPaCa-2 cells. After treatment, the expression of the K-ras gene, cell proliferation, migration and invasion were reduced while the population of apoptotic cells was enhanced. Furthermore, by exploiting the unique absorption at 650 nm, the GQDs can serve as photothermal agents that can serve as a trigger to release the DOX and siRNA from the GQD/DOX/BCPV/siRNA nanocomplex under near-infrared light (NIR) irradiation. The synergistic therapeutic effects of the GQD/DOX/BCPV/siRNA nanocomplex were found to be enhanced under NIR light irradiation. In the second section of the thesis, novel water-soluble CsPbBr3 nanocrystals were developed for targeted single and multiphoton imaging of cancer cells. Optical imaging is a non-invasive technique for visualizing cancer cells and investigating physiological processes in vitro and in vivo. An ideal optical fluorescent agent typically requires high photoluminescence quantum yield, excellent colloidal stability, long-term photostability, and exhibit multiphoton absorption. In the past decade, perovskite has been gaining huge attention for applications such as solar cells, light-emitting diodes, and photodetectors. However, their highly ionic properties have rendered the material to be highly susceptible to degradation when in contact with water and oxygen. To counter this, we present novel water-soluble CsPbBr3 nanocrystals prepared by first coating the CsPbBr3¬¬¬¬ nanocrystals with a silica shell followed by PEGylation in a phospholipid micelle. The resultant nanocrystals exhibited multiphoton absorption property, which is highly desirable for biological imaging due to the higher penetration depth, lower autofluorescence, improved sensitivity, enhanced resolution, and lower phototoxicity. The CsPbBr3/SiO2/mPEG-DSPE demonstrated good aqueous stability and photostability under various test conditions, i.e., long-term aqueous stability, continuous UV irradiation, and continuous ultrasonication. The CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals were also found to be stable after being dispersed in various biological mediums. The cytotoxicity CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals were evaluated using MTT assay in four different cell lines, including PANC-1, Mia PaCa-2, RAW264.7, and CaCo-2 cells. Next, the CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals were employed as a fluorescent label for targeted single and multiphoton imaging of cancer cells. In the last section, the focus of the thesis is directed towards the approach of using nanoparticles for sensing applications. We first investigated the potential use of CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals for the fluorescence detection of color additives in water samples and food products. Color additives, also known as dyes, can be a major contributor of toxic species to the environment. In the textile industry alone, a large amount of wastewater containing residual dyes is being discharged into rivers and streams, affecting the light penetrating the water and subsequently affecting the natural ecosystem and polluting the water source. Moreover, color additive such as Rhodamine 6G (R6G) is used in food that is often targeted at children. R6G is a derivative of xanthene dyes and can potentially affect the reproductive and development growth in human. Henceforth, we fabricated water-stable CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals as a ratiometric fluorescence sensor to detect the presence of R6G. The emission of the CsPbBr3/SiO¬2/mPEG-DSPE at 518 nm decrease linearly while a new peak at 565 nm increase linearly in the presence of a concentration of R6G. The proposed nanosensor has a detection limit of 0.01 ppm and a linear operating range from 0 to 10 ppm. Other common color additives were also added to the CsPbBr3/SiO¬2/mPEG-DSPE solution and no significant changes in fluorescence intensity were observed, indicating the high selectivity of the nanosensor towards R6G. The CsPbBr3/SiO¬2/mPEG-DSPE nanosensor was also employed to detect the presence of R6G in real food and water samples that contain complex backgrounds such as dissolved nutrients and metal ions. The FRET detection mechanism was also investigated by measuring the lifetime of CsPbBr3/SiO¬2/mPEG-DSPE in the absence and presence of R6G. Lastly, this section also explored the use of carbon dots as a fluorescence sensor for the detection of ferric ions in water samples and intracellularly. Excessive intake of iron is detrimental to human health, leading to many serious diseases such as hemochromatosis leading to liver damage, increased inflammatory markers, and weakened cognitive and motor growth in children. While water that is heavily contaminated by iron is easily detectable owing to the unpleasant taste and stain, trace-level iron contamination in water may not be visible to the naked eyes and long-term exposures remain dangerous to the public. In this work, a facile one-step microwave-assisted pyrolysis is adopted to produce fluorescent carbon dots as a highly sensitive fluorometric sensing probe for Fe3+ ions in aqueous solution. The carbon dots were carefully characterized by transmission electron microscopy, UV-Vis spectrometry, Raman spectrometry, Fourier-transform infrared spectroscopy, X-ray photoelectron spectrometry, and fluorometer. The fluorescence of the carbon dots was found to decrease with increasing concentration of Fe3+ ions. The LOD was determined to be 0.16 µM with a linear operating range from 0 – 500 µM. It was also found that by employing a pH tuning technique, the selectivity of the sensing probe towards Fe3+ was significantly improved by reducing the interference effect of Cu2+, Co2+, and Ag+. The carbon dots were also employed as a fluorescent agent for cellular imaging and can be used as a semi-quantitative fluorescent probe for intracellular detection of Fe3+ ions in Mia PaCa-2 cells. In summary, this thesis mainly focused on achieving three different photonic applications including cancer therapeutics, multiphoton cellular imaging, and sensing using polymeric, carbon, and perovskite-based nanoparticles. We envisioned that these works can further unveil the potential for future translation of these nanomaterials into commercial photonics applications.||URI:||https://hdl.handle.net/10356/145841||DOI:||10.32657/10356/145841||Rights:||This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).||Fulltext Permission:||embargo_20230111||Fulltext Availability:||With Fulltext|
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