|Title:||Molybdenum disulfide based nanoprobes for biosensing and bioimaging|
|Subject:||Hong Kong Polytechnic University -- Dissertations|
|Department:||Department of Biomedical Engineering|
|Pages:||xxiv, 146 pages : color illustrations|
|Abstract:||During the past decade, the applications of graphene-based nanomaterials bloomed in the biosensing and bioimaging fields due to their unique electronic and optical properties. Recently, molybdenum disulfide (MoS₂) as another kind of 2D single-layered nanomaterial has attracted tremendous attention because of its structure analogous to graphene and many good properties such as high absorbance in the NIR region, good thermal conductivity, excellent water solubility and biocompatibility. However, the bio-applications of MoS₂ nanomaterials are still at the initial stage. More efforts are still needed to explore the potential applications of MoS₂ in biosensing, bioimaging and therapeutics fields. In this thesis, two types of MoS₂ based nanoprobes were developed for the applications of biosensing, bioimaging and therapeutics, including MoS₂ nanosheets based nanoplatform for epithelial cell adhesion molecule (EpCAM) protein detection and MoS₂ nanosheet coated gold nanorod (MoS₂-AuNR) based photoacoustic imaging and photothermal therapeutic agent for pain imaging and medication in osteoarthritis (OA). To explore MoS₂ based nanoplatform for biosensing application, we presented a "turn-on" fluorescence resonance energy transfer (FRET) biosensing platform with graphene quantum dots (GQDs) as fluorescence donor and MoS₂ nanosheets as fluorescence acceptor for rapid and sensitive detection of Epithelial Cell Adhesion Molecule (EpCAM) protein as a circulation tumor cell (CTC) biomarker. The GQD-aptamer-MoS₂ sensing platform was realized by adsorption of PEGylated GQD labeled EpCAM aptamer onto MoS₂ nanosheet surface via physical absorption. The close distance between GQD and MoS₂ nanosheet triggered the FRET effect with fluorescence "OFF" state. The detection of EpCAM protein was realized by monitoring the change of fluorescence signal, which resulted from the detachment of GQD-aptamer from MoS₂ nanosheet surface due to the specific affinity interaction between GQD-aptamer and EpCAM protein. The target EpCAM protein can be detected sensitively and selectively with the linear detection range from 3 nM to 53 nM. The limit of detection (LOD) was calculated as 450 pM.|
To explore MoS₂ based nanoprobe for near infrared (NIR) photoacoustic (PA) bioimaging application, we reported a novel hybrid MoS₂ coated gold nanorods (AuNRs) with strongly amplified PA signal for in vivo bioimaging. Due to the enhanced photothermal conversion efficiency and the reduced interfacial thermal resistance with water, the hybrid MoS₂ coated AuNR (MoS₂-AuNR) nanosystem showed excellent photostability and significantly enhanced photoacoustic imaging signal compared with bare AuNR both in vitro and in vivo. MoS₂-AuNR nanosystem could be internalized by cells easily and exhibited much lower cytotoxicity compared with bare AuNR due to the coating with the biocompatible MoS₂ layer. Moreover, the biodistribution study revealed that MoS₂-AuNR mainly accumulated in liver and spleen after intravenous injection. The histological evaluation revealed no obvious organ damage or lesions for MoS₂-AuNR treated mice. We further explored MoS₂-AuNR based nanoprobe for PA image-guided photothermal therapy for osteoarthritis (OA) pain release in an OA knee mice model. To target nerve ending in OA knee, anti-nerve growth factor (NGF) antibody was conjugated with MoS₂-AuNR nanoprobe. The hypothesis was that anti-NGF antibody conjugated MoS₂-AuNR nanoprobes could selectively target the over-expressed NGF in the inflammatory OA knee due to the specific interaction between anti-NGF antibody and NGF antigen. PA imaging could be used to monitor the targeting process of functionalized nanoprobes and NIR laser-based phototherapy could then be performed to destroy overexpressed NGF for pain release. The in-vivo experiment with intravenous injection of anti-NGF antibody conjugated MoS₂-AuNR nanoprobes was then performed in an OA knee mice model. The PA imaging results demonstrated that anti-NGF antibody conjugated nanoprobes could selectively target the inflammatory OA knee with much higher PA signal compared with control knee. The therapeutic effect of the OA knee after NIR laser treatment with anti-NGF antibody conjugated nanoprobes targeting was evaluated by the behavioral pain sensitivity in response to mechanical stimuli and the motor coordination using monofilaments test and rotarod performance test, respectively. The results showed an obvious improvement of the pain behavior of OA knee mice after nanoprobe-targeting and NIR light treatment. Moreover, the accumulation of anti-NGF antibody conjugated nanoprobes in OA knee and major organs (e.g., liver and spleen) was testified by biodistribution study at different time points. No apparent organ damage or inflammation was observed for anti-NGF Ab-MoS₂-AuNR treated mice through histological evaluation. Therefore, anti-NGF antibody coated MoS₂-AuNR nanoprobe could act as a potential PA imaging guided photothermal therapeutic agent for pain imaging/medication in OA.
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