Font Size: a A A

Design, Synthesis And Biological Applications Of Molecules And Nano Fluorescent Probe

Posted on:2015-02-24Degree:MasterType:Thesis
Country:ChinaCandidate:F WangFull Text:PDF
GTID:2254330425996177Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
In the process of the growth of malignant tumor, transformation between epithelial tomesenchymal cell (EMT) due to hypoxia, is being more and more attention. However, the lack ofeffective detection methods for detecting hypoxic tumor cells, thus impeding the study of thecell depends on the mechanism of oxygen EMT. So we designed a near-infrared fluorescentprobe (Cy-NO2) by detecting nitroreductase hypoxic tumor cells for fluorescence imaging.Nitroreductase detection mechanism is reduced to an amino group, and nicotinamide adeninedinucleotide as the electron source based on the selective catalytic nitro. The probenitroreductase strong fluorescence enhancement of selectivity and sensitivity of the probe ismore important EMT investigated the relationship between success and between the intracellularoxygen levels. Certain intracellular proteins to a certain extent cyanine fluorescent imagingprobe, core-shell nano-porous structure of the fluorescent probe-coated silica can be reduced oreven eliminated this effect.This paper reviews the current situation and development trend of fluorescent probes todetect hypoxia. Fluorescent probes for molecular analysis of biochemical and biologicalfluorescence imaging system analysis, and molecular probes designed and synthesized based ona novel mesoporous silica-molecule fluorescence probes. Follows:This paper presents a near-infrared fluorescent probe (Cy-NO2)by detecting nitroreductasehypoxic tumor cells for fluorescence imaging. Nitroreductase hypoxia detection mechanism isbased on the selective catalytic reduction of the nitro group to an amino group and nicotinamideadenine dinucleotide as the electron source in the reduction process. The probe nitroreductasestrong fluorescence enhancement of selectivity and sensitivity of the probe is more importantsuccess EMT and investigated the relationship between the intracellular oxygen levels betweenarticle2-(2-nitroimidazole) ethylamine as the nitroreductase (NTR) having a specificresponse group, and the precursor to the cyanine fluorophore is designed and synthesizednear-infrared fluorescent probes used to indicate the area of hypoxic tumor this probe because of its launch in the near infrared region, however autofluorescence general organism is not in thenear infrared region, thus avoiding the probe in terms of biological autofluorescence has itsunique advantages. When the oxygen concentration is relatively low, in biochemical systemsnitro group with added liver microsomes and NADPH reaction, reduction of a nitro group to anamino group is specifically; vivo, nitro reductase coenzyme (nicotinamide adeninedinucleotide NADH) final reduction of the nitro group to an amino group. Using theelectron-withdrawing effect of the nitro and amino, and for differences in the nature ofelectronic effect on the fluorescence produced by the probe: nitro cyanine strong quenching ofthe fluorophore of the probes that weak fluorescence hypoxia, the nitro group is reduced to anamino group, the fluorescence rapidly increases, and thus the success of the detection of lack ofoxygen. In liver microsomes and NADPH system, liver microsomes concentration range is0-13μg/mL, the linear equation F=37.466+16.118[livermicrosomes](μg/mL), the linearcorrelation coefficient of0.9989, the detection limit of0.65ng/mL, for the description of lowerconcentrations of probe may be detected nitroreductase. Moreover, some in vivo reducingsubstances: VC, GSH, Arg, DTT, etc. without interference of the probe. By cytotoxicity assaysunder normoxic conditions of hypoxia and anoxia can be seen in the probe has goodbiocompatibility and high water solubility, low toxicity, can be visualized research on theextent of hypoxic cells within. EMT proved able to monitor the probe some of the changes ofintracellular proteins associated with EMT by monitoring hypoxia.Because the lack of anti-nitroimidazole molecular oxygen probe light bleachingperformance is poor, a low quantum yield, and the cell contents are susceptible to a number ofprotein molecules in a high fluorescence background, thus largely limiting the SNR of the probe,so we designed a probe hypoxia coated mesoporous silica((Cy-NO2@SiO2)), the specificprogram is coated nitroimidazole hypoxic probe inside the mesoporous silicon, and outside itmacromolecular protein isolate, but can also be nitroreductase hypoxia probe electron transferthrough the tunnel and nitroimidazole, so that the probe molecules emit strong fluorescence isreduced because of large proteins can mesoporous silicon inside the nitroimidazole hypoxiaprobe impact, so this scheme can effectively reduce background fluorescence due to theinterference generated by the probe, and molecular probes and nano materials connected torestrict the rotation of its structure to improve the anti-light probe bleaching performance, improved quantum yield, can greatly improve the signal to noise ratio of the probe in addition tothe probe has good biocompatibility, can effectively avoid the large proteins to intracellularfluorescence imaging interference of the probe, to a large extent reduce the fluorescencebackground of the probe, so the probe can be effectively used imaging hypoxic cells, there is agood prospect in the detection of tumor hypoxia.
Keywords/Search Tags:2-nitroimidazole, cyanine, near-infrared fluorescent probes, mesoporous silica
PDF Full Text Request
Related items