Preparation Of Molybdenum Disulfide Quantum Dots And Its Application In Biological Imaging And Drug Delivery

Transition metal chalcogen compounds,especially molybdenum disulfide（MoS₂）,have recently received wide attention from researchers due to their unique intrinsic properties.As a nano-scale MoS₂ material,MoS₂ quantum dots（MoS₂ QDs）change the electronic structure of the material due to its strong quantum confinement effect and boundary effect,and make it more physicochemical properties.In particular,the lumine-scent properties of MoS₂ QDs make it a promising application in biomedical imaging.However,the preparation methods of the existing MoS₂ QDs are still not mature enough,and there are problems such as low yield,uncontrollable size,difficulty in removing organic solvents,and easy agglomeration.Therefore,it is of great significance to explore more effective methods for preparing MoS₂ QDs and further expand their application fields.In this paper,the preparation and fluorescence properties of MoS₂ QDs and polyethylene glycol（PEG）functionalized MoS₂ QDs（MoS₂-PEG）were studied systema-tically.The applications of MoS₂ QDs and MoS₂-PEG in biological imaging and drug delivery were discussed.The main content of this paper is divided into the following four parts:1.Firstly,Three kinds of MoS₂ QDs were prepared by different methods.（There are MoS₂ QDs 1,2 and 3 which were prepared by hydrothermal method using ammonium tetrathiomolybdate as precursor,solvothermal method from top to bottom and one-step hydrothermal method using sodium molybdate as precursor,respectively.）.Their structure,morphology and optical properties were systematically characterized.The results show that MoS₂ QDs 2 is more uniform in size,while MoS₂ QDs 1 and MoS₂ QDs 3 have smaller average size and better water solubility.However,MoS₂ QDs 1 is extremely unstable after being dried to a solid and is easily oxidized.These three MoS₂ QDs all show blue fluorescenceand MoS₂ QDs 3 has the highest fluorescence intensity.2.For the first time,the drug delivery system（MoS₂-DOX）was constructed by directly using MoS₂ QDs as a drug carrier and using the hydrophobic interaction between MoS₂ QDs and drug molecules to load DOX.The feasibility of MoS₂ QDs 1 and MoS₂QDs 2 as drug carriers was studied by cytotoxicity test,cell imaging and in vitrodrug release.The results show that the drug loading of MoS₂ QDs 1 and MoS₂ QDs 2 is 72.8%and 56.7%,respectively.The cytotoxicity of MoS₂-DOX is lower than that of free DOX.MoS₂-DOX shows obvious pH-responsive release behavior,that is,the release rate of DOX in acidic environment is significantly higher than that in pH=7.4.This property of the drug delivery system allows it to improve therapeutic efficiency without increasing the dose of DOX while reducing adverse reactions of anticancer drugs to normal tissues.Compared these two drug-loading systems,the one with MoS₂ QDs 1 as the carrier releases slowly,but the drug release amount is high,while another one with MoS₂ QDs 2as the carrier releases quickly,but the drug release amount is slightly lower.3.The PEG-modified MoS₂ QDs（MoS₂-PEG）were obtained by using MoS₂ QDs 3and PEG as raw materials and glutaraldehyde as a coupling agent.The structure,morphology,chemical composition,thermal stability and optical properties were systema-tically characterized.The results show that MoS₂-PEG has a regular spherical shape and a uniform distribution with an average particle size of 123.5 nm.These nanospheres consist of individual nanoparticles coated with the PEG matrix.The quantum yield of MoS₂-PEG is 3.5%.The stability of MoS₂-PEG in physiological environment is obviously better than that of MoS₂ QDs 3,and it is more suitable for biomedical application.4.The drug delivery system（MoS₂-PEG-DOX）was constructed by using MoS₂-PEG as a drug carrier and DOX as model drug.The advantages and feasibility of MoS₂-PEG as a drug carrier were studied by cytotoxicity experiment,in vitro drug release and cell imaging.The results show that the toxicity of MoS₂-PEG is significantly lower than that of MoS₂ QDs.When the concentration is as high as 1.5 mg/m L,the survival rate of U251human glioma cells is still above 82%.The drug loading of MoS₂-PEG-DOX is 71.6%andits cytotoxicity is lower than that of free DOX.MoS₂-PEG-DOX shows significant pH-responsive release behavior.The total amounts of DOX released after 48 h are 74.7%,53.9%,and 19.0%at pH values of 5.0,6.0,and 7.4,respectively.Based on the intrinsic fluorescence of MoS₂-PEG and DOX,MoS₂-PEG-DOX can also exhibit dual-color imag-ing for revealing the intracellular localization of MoS₂-PEG and DOX release.After 16 h of incubation of U251 human glioma cells with MoS₂-PEG-DOX,most DOX is distributed in the cell nuclei,while MoS₂-PEG remains in the cytoplasm.The results indicate that MoS₂-PEG is expected to be used as a pH responsive fluorescent drug carrier,which have better biocompatibility and physiological stability than MoS₂ QDs,in the field of cell imaging and drug delivery.