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Biocompatible luminescent probes for imaging and inhibition of cancersGoetz, Joan 23 August 2018 (has links)
This joint PhD program is part of a collaboration between Hong Kong Baptist University (Dr. Gary K-L Wong) and Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse (LIMAA - Dr. Loïc Charbonnière) funded by the Alsace region to synthesize new nanoprobes for sensing, imaging, and inhibiting cancer diseases. The first work was to synthesize new hybrid ultrabright nanoparticles. They have been obtained from a La0.9Tb0.1F3 core and coated by different ligands. Thanks to a mechanism of antenna effect, the brightness of the nanoparticles has been significantly improved. The second work was to synthesize a new ligand to photosensitize water-soluble La0.90Eu0.1F3 nanoparticles in order to improve the emission of europium. A second ligand and new heterometallic nanoparticles have been synthesized with the aim to promote the energy transfer from Tb(III) ions on the surface of the NPs to Eu(III) ions in the core of the nanoparticles and to get a very long excited-state lifetime and an exceptional quantum yield in aqueous solution. The last work was to functionalize water-soluble graphitic-carbon nitride (g-C3N4) nanoparticles by porphyrins. The porphyrins have been synthesized to generate singlet oxygen (1O2), to host a Ga3+ ion inside their cavity and with two different linkers to be coupled to nanoparticles. This system aims to be a pH sensor, and a PDT and PET theranostic agent.
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Nanoparticles assisted disease biomarkers sensing by microscopic and spectrometric methodsPoon, Chung Yan 23 August 2016 (has links)
Nanoparticles has drawn attention in the past few decades for their large surface area-to-volume ratio, unique optical property, fast mass transportation and etc. They are widely applied in biomedical field as they are excellent signal transducers. Among all detection approaches, fluorescence detection, especially fluorescence resonance energy transfer (FRET), is one of the most popular approaches for their great convenience. In the first detection scheme, a well-designed nanoprobe was utilized for direct trypsin quantification. Herein, a graphene quantum dot (GQD) applied as a donor while a coumarin derivative, CMR2, acted as an acceptor. Moreover, bovine serum albumin (BSA), as a protein model, was not only considered as a linker for the donor-acceptor pair, but also a fluorescence enhancer of the quantum dots and CMR2. In the presence of trypsin, BSA was digested, thus, the FRET system was destroyed. Consequently, the emission peak of the donor was regenerated while the emission of the acceptor was reduced. The trypsin was quantified by a ratiometric measurement for two emission peaks. The detection limit of trypsin was 0.7 g/mL, which is 0.008-fold of the average trypsin level in acute pancreatitis patient's urine. Moreover, the approach was proved to be highly selective, suggesting a high potential for fast and low cost clinical screening. On the other hand, the optical property of nanoparticle has captured a great attention as its light scattering is highly sensitive to local dielectric environment. Two light scattering based detection approaches were demonstrated, including simple counting method and plasmonic scattering enhancement method. For simple counting method, antibody modified nanoparticle was applied to target antigen, providing a sensitive but direct approach for cancer biomarkers quantification. As a proof of concept, prostate-specific antigen (PSA) was chosen as an example. Antibody-conjugated silver nanoparticles (AgNP-Ab) were served as the probe to capture PSA, forming AgNP-Ab-PSA complexes. Since the number of complexes was corresponding to the amount of PSA, the antigen was quantified by counting the number of silver nanoparticle under dark field microscopy (DFM) coupled with charge-coupled device (CCD) camera. The detection limit of 9 pM of this assay was well below the PSA threshold of prostate cancer patient, suggested the feasibility of our assay in diagnosis application. Besides counting of nanoparticle, the scattering intensity of nanoparticle is also informative. In the third assay, immobilized capture antibody-conjugated gold nanoparticles (AuNP-Abcapture) were firstly utilized in capturing the target analyte, followed by the introduction of strong scattering detection antibody-conjugated silver nanoparticles (AgNP-Abdetection). In the presence of the corresponding antigen, the two metallic probes sandwiched the antigen and stayed at close proximity, resulting a strong plasmonic coupling effect of those nanoparticles. Consequently, the scattering intensity of gold nanoprobe was greatly enhanced. The antigen was quantified by measuring the intensity change before and after the immunoreaction. To demonstrate the high flexibility of this assay, several antigens including carcinoembryonic antigen (CEA), PSA and alpha fetoprotein (AFP) were quantified with this method, giving detection limit at 1.7 pM, 3.3 pM and 5.9 pM respectively, which were much lower than their cut-off levels of corresponding diseases. Detections of CEA, PSA and AFP in real sample were demonstrated, suggesting a high potential in clinical application.
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A Study of the Synthesis and Surface Modification of UV Emitting Zinc Oxide for Bio-Medical ApplicationsJohn, Sween 05 1900 (has links)
This thesis presents a novel ZnO-hydrogel based fluorescent colloidal semiconductor nanomaterial system for potential bio-medical applications such as bio-imaging, cancer detection and therapy. The preparation of ZnO nanoparticles and their surface modification to make a biocompatible material with enhanced optical properties is discussed. High quality ZnO nanoparticles with UV band edge emission are prepared using gas evaporation method. Semiconductor materials including ZnO are insoluble in water. Since biological applications require water soluble nanomaterials, ZnO nanoparticles are first dispersed in water by ball milling method, and their aqueous stability and fluorescence properties are enhanced by incorporating them in bio-compatible poly N-isopropylacrylamide (PNIPAM) based hydrogel polymer matrix. The optical properties of ZnO-hydrogel colloidal dispersion versus ZnO-Water dispersion were analyzed. The optical characterization using photoluminescence spectroscopy indicates approximately 10 times enhancement of fluorescence in ZnO-hydrogel colloidal system compared to ZnO-water system. Ultrafast time resolved measurement demonstrates dominant exciton recombination process in ZnO-hydrogel system compared to ZnO-water system, confirming the surface modification of ZnO nanoparticles by hydrogel polymer matrix. The surface modification of ZnO nanoparticles by hydrogel induce more scattering centers per unit area of cross-section, and hence increase the luminescence from the ZnO-gel samples due to multiple path excitations. Furthermore, surface modification of ZnO by hydrogel increases the radiative efficiency of this hybrid colloidal material system thereby contributing to enhanced emission.
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