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Quantum Dot Based Fluorescent Diagnosis Of Lung Cancer And Analysis Of Methotrexate

Posted on:2018-09-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:S Y ZouFull Text:PDF
GTID:1314330533961544Subject:Biomedical engineering
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Cancer is a complex disease featured with the accumulation of multiple molecular changes due to genetic variations and environmental pollution or poor living habits.The current diagnostic level and prognostic classification does not meet the diversity of clinical manifestations of the tumor and can hardly predict the outcome of the treatment.Furthermore,most anti-cancer drugs cannot effectively differentiate cancerous cells and normal cells,inevitably resulting in systemic toxicity and serious side effects.In addition,cancer often lacks obvious symptoms in the early stages.Usually in the treatment,cancer cells have been invaded and transferred to other parts of the body.For example,when there is a clinical manifestation,more than 60% of patients with breast cancer,lung cancer,colon cancer,prostate cancer and ovarian cancer have hidden or significant metastatic lesions.At this stage,the treatment effect has been relatively limited.For those reasons,cancer has become the main cause of adult death.The World Health Organizat ion(WHO)has reported more than 14 million cancer diagnoses worldwide in 2012,and cancer patients and deaths are all disturbingly increased,with nearly half of new cancer cases occurring in Asia,most of them in China.However,if the cancer can be diagnosed early and treatment timely,the survival rate of patient will be greatly improved.For example,non-small cell lung cancer is responsible for the most of cancer-related deaths worldwide,with only 5-15% and <2% 5-year survival rates for stage III and V patients,respectively.In contrast,patients who started treatment in the early stage of disease,such as stage I,can signif icantly improve survival rates,with an average 80% of the 5-year survival rate.Therefore,the key to effective reducing the death of cancer patients is the diagnosis cancer as early as possible.In recent years,early diagnosis of cancer has made some progress and common diagnostic methods include imaging(such as magnetic resonance imaging,CT imaging and computed tomography),microscopic examination(such as bronchoscopy,thoracoscopy and mediastinoscopy),and cell detection.But the sensitivity of imaging and microscopic examination is low,and the ability to distinguish benign and malignant lesions is limited.Obvious ly,it is the most effective diagnose method by direct detection cancer cells.To this end,we mainly carried out the following research work:1)The nitrogen-doped carbon dots with good biocompatibility were prepared using citric acid as the carbon source and diethylenetr iamine as the nitrogen source.The functionalized fluorescent probes for folic acid were prepared by quenching the fluorescence of carbon quantum dots.By means of the difference of the cancer cells and normal cells in the folic acid receptor expression,the prepared fluorescent probe can effectively identify folate cancer cells and normal cells,which is useful in cancer diagnosis.2)The doping carbon quantum dots,CdTe quantum dots,Mn doping ZnS quantum dots were functionalized with folic acid,sodium hyaluronate and aptamers to form several fluorescent probes,respectively.With the help of graphene oxide,a novel fluorescence s ensor array was constructed by means of the fluorescent probes.With the aid of the principal component analysis,NLCH-1299(human non-small cell lung cancer cell),H460(human large cell lung cancer cell)and H446(human small cell lung cancer cell)and human normal embryonic lung cell MRC-5 were differentiated by the fluorescent sensor array which can be used as an adjunct to cancer diagnosis.3)On the basis of the differentiation of folic acid receptor overexpressing cells with the folic acid functionalized carbon quantum dots,a fluorescent based theranostic platform was proposed.With the help of polystyrene microspheres were used as hard template,CTAB was used as mesoporous guide agent,and the hydrolysis of TEOS and(3-aminopropyl)triethoxysilane,hollow microspheres were prepared by removing PS microspheres and CTAB by high temperature sinter ing.The N,S-co-doped carbon dots-folic acid functionalized f luorescent probes were grafted onto the hollow mesoporous silica microspheres which is filled with thermosensitive gel to obtain a composite which can be used as a fluorescent assay after the chemotherapeutic agent is loaded on.The structure,the behavior of drug release,cytotoxicity and fluorescent imaging of the diagnostic reagents were studied.We hope our research can provide some basic research for personalized medicine for the benefit of patients.4)The N,S co-doped carbon dots were synthesized from L-cysteine and citric acid and applied to an on-off fluorescent probe to determine chemotherapeutic drug methotrexate based on methotrexate quenching the fluorescence of the N,S co-doped carbon dots.Under optimized conditions,the fluorescent probe shows very good sensitivity and s electivity and the detection mechanism was studied in details.5)Carbon dots doped with nitrogen and sulfur(NSCDs)was prepared from L-cysteine with a hydrothermal method and applied to develop a fluorescent sensor to determine fluazinam.Characterizations of the NSCDs suggest that it provides abundant affinitive sites for recognizing fluazinam and strong inner filter effect(IFE)leads fluazinam to quench the fluorescence of the NSCDs with high efficiency.Under optimized conditions,the fluorescent probe shows very good sensitivity and selectivity.Besides,NSCDs could also be used to fabricate visual paper-based testing stripes under a portable UV lamp.
Keywords/Search Tags:Quantum dots, Lung cancer diagnosis and treatment, Flurorescent detection, pharmaceutical analysis, nanoprobe
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