Functionalization of Low-Dimensional Nanomaterials of MoS2 with Thiol-Terminated Molecules for Biomolecular Detection, Cellular Imaging, and Drug Delivery
| Autor: | Shih-Chiang Chen, 陳世強 |
|---|---|
| Rok vydání: | 2017 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 105 (I) 6-Mercaptopurine-induced fluorescence quenching of monolayer MoS2 nanodots: applications to glutathione sensing, cellular imaging, and glutathione-stimulated drug delivery Molybdenum disulfide (MoS2) nanodots (NDs) with sulfur vacancies have been demonstrated to be suitable to conjugate thiolated molecules. However, thiol-induced fluorescence quenching of MoS2 NDs has been rarely explored. In this study, 6-mercaptopurine (6-MP) served as an efficient quencher for monolayer MoS2 (M-MoS2) NDs that were highly fluorescent in an aqueous solution. 6-MP molecules were chemically adsorbed at the sulfur vacancy sites of the M-MoS2 NDs. The formed complexes triggered the efficient fluorescence quenching of the M-MoS2 NDs due to acceptor-excited photoinduced electron transfer. The presence of glutathione (GSH) efficiently triggered the release of 6-MP from the M-MoS2 NDs, thereby switching on the fluorescence of the M-MoS2 NDs. Thus, the 6-MP-M-MoS2 NDs were implemented as a platform for the sensitive and selective detection of GSH in erythrocytes and live cells without the interference of cysteine. Additionally, thiolated doxorubicin (DOX-SH)-loaded M-MoS2 NDs (DOX-SH/M-MoS2 NDs) efficiently liberated DOX-SH in the presence of 5 mM GSH, indicating that the DOX-SH/M-MoS2 NDs served as GSH-responsive nanocarriers for DOX-SH delivery. In vivo studies revealed that the DOX-SH/M-MoS2 NDs exhibited efficient uptake by HeLa cells and greater cytotoxicity than free DOX-SH. Intracellular and in vivo GSH-induced release of DOX-SH from DOX-SH-loaded M-MoS2 NDs was further validated by confocal laser scanning microscopy and IVIS spectrum system, respectively. Given the excitation- dependent fluorescence behavior of the M-MoS2 NDs, the DOX-SH/M-MoS2 NDs could be implemented for simultaneous drug delivery and cellular imaging. (II) Functionalization of MoS2 nanosheets with aptamer as FRET-based nanoprobe for potassium ions sensing and imaging The potassium ion plays an important role in many physiological functions such as systemic blood pressure control, homeostasis in the muscle, glucose and insulin metabolism, and hyperpolarization of neurons, and therefore the development of a method to monitor K+ in a cell is extremely important. Here, we combine MoS2 nanosheets (MoS2 NSs) with a aptamer-based Förster resonance energy transfer (FRET) nano-probe (D-Apt-A/cDNA-SH), we designed a novel ratiometric fluorescent nanoprobe, termed as an “D-Apt-A/cDNA-SH-MoS2 NSs”, for sensing and imaging K+ concentration values in human serum and living cells, respectively. The D-Apt-A/cDNA-SH-MoS2 NSs consist of a MoS2 NSs, thiolated single-stranded oligonucleotides (cDNA-SH), and dual-dye-labeled aptamer, while FAM conduct as FRET donor (D) and TAMRA (A) as acceptor (D-Apt-A). The cDNA-SH are designed to bind with the D-Apt-A and immobilized on the MoS2 NSs surface via an ligand conjugation. In the absence of target K+, the D-Apt-A are captured by seized with the cDNA-SH, increasing the distance of FAM and TAMRA, inducing a very low FRET efficiency. In this state, only the fluorescence of FAM can be detected. However, in the presence of target K+, the D-Apt-A are gradually replaced from the cDNA-SH, then forming G-quadruplex structures that induce FAM and TAMRA move into closer position with each other, and result in a high FRET efficiency. In this state, the fluorescence of the TAMRA can be clearly detected. Thus, the intensity of fluorescence ratio of acceptor to donor (IFA/IFD) can be used as a signal for detection of target K+. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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