CN110161005A - It is a kind of to detect the fluorescent carbon point of cell activity, preparation method and applications - Google Patents
It is a kind of to detect the fluorescent carbon point of cell activity, preparation method and applications Download PDFInfo
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Abstract
The present invention provides a kind of fluorescent carbon points for detecting cell activity, preparation method and applications, by 2,4- 4-dihydroxy benzaldehyde and 1,2,3,3- tetramethyl -3H- iodate indoles are dissolved in dehydrated alcohol, microwave reaction 1h, purified after cooling with filter membrane, rotary evaporation obtains wine-colored carbon dots solid, is dissolved in DMSO as stock solution.Carbon dots of the present invention synthesize very simple, convenient for operation；The present invention can detect cell activity；The present invention can be by the film potential of highly sensitive monitoring mitochondria, to distinguish health, apoptosis and dead cell.
Description
Technical field
The present invention relates in fluorescent carbon point and biosensor technique field, and in particular to a kind of fluorescence for detecting cell activity
Carbon dots, preparation method and applications.
Background technique
Mitochondria is the power station of cell, plays key effect in many important bioprocess.Injury of mitochondria and
Dysfunction and a series of diseases, such as: cancer, diabetes, Alzheimer disease and Parkinson's disease, myocardial ischemia-reperfusion damage
Wound and aging degenerative disease etc. are closely related.The reduction and disappearance of mitochondrial membrane potential represent injury of mitochondria and cell is dead
It dies.Therefore, the method for monitoring mitochondrial membrane potential variation is extremely important.
Carbon dots are easy to surface modification and low cost due to hypotoxicity, good biocompatibility, excellent photostability
Advantage has been widely used for bio-imaging.
Up to the present, although there are the carbon dots of some reports that can perceive the reduction of mitochondrial membrane potential, may not be used
Sensitively, selectively to show three kinds of different levels of mitochondrial membrane potential, i.e., normally, reduce and disappear and they
Application in mitochondria related biological processes.
Therefore the present invention intends solving such problem, passes through the targeting feelings of carbon dots organelle in different health status
Condition, to reflect cell viability, distinguishes health, apoptosis and dead cell for detecting mitochondrial membrane potential.
Summary of the invention
The invention proposes a kind of fluorescent carbon point for detecting cell activity, preparation method and applications, benzaldehyde derivatives
Carbon dots can be generated, 1,2,3,3- tetramethyl -3H- indoles has the ability of targetted mitochondria, synthesizes carbon using the two condensation
Point can monitor to efficient and sensible the film potential of mitochondria, while by the positioning in different organelles, realizing and distinguishing health
Cell, apoptotic cell and dead cell.
Realize the technical scheme is that
A kind of preparation method for the fluorescent carbon point detecting cell activity, by 2,4- 4-dihydroxy benzaldehyde and 1,2,3,3- tetramethyls
Base -3H- iodate indoles is dissolved in dehydrated alcohol, microwave reaction 1h, is purified after cooling with filter membrane, rotary evaporation obtains dark red
The carbon dots solid of color is dissolved in DMSO as stock solution.
Fluorescent carbon point synthetic route based on detection cell activity is as follows:
2, the 4- 4-dihydroxy benzaldehyde and 1, the molar ratio of 2,3,3- tetramethyl -3H- iodate indoles are 3:1.
The microwave reaction temperature is 130 DEG C, is purified after cooling with 0.22 μM of filter membrane.
The fluorescent carbon point realizes monitoring mitochondrial membrane potential by the positioning in different organelles, distinguishes health, withers
It dies and dead cell.
Above-mentioned application specifically includes:
The targeting situation for testing carbon dots organelle in different health status respectively, monitors mitochondrial membrane potential, with reflection
Cell viability distinguishes health, apoptosis and dead cell.There is good prospect in biomedical research and the diagnosis of related disease.
The beneficial effects of the present invention are: (1) carbon dots synthesize very simple, convenient for operation；(2) it is living to detect cell by the present invention
Property；(3) present invention can be by the film potential of highly sensitive monitoring mitochondria, to distinguish health, apoptosis and dead cell.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention for those of ordinary skill in the art without creative efforts, can be with
It obtains other drawings based on these drawings.
Fig. 1 is the TEM map of 1 carbon dots of embodiment.
Fig. 2 is the IR map of 1 carbon dots of embodiment.
Fig. 3 is the XPS map of 1 carbon dots of embodiment.
Fig. 4 is 1 carbon dots of embodiment (5 μ g mL-1) ultraviolet and fluorescence spectra in PBS (10mM pH=7.4).
Fig. 5 is the fluorescence lifetime map of 1 carbon dots of embodiment.
Fig. 6 is the photostability map of 1 carbon dots of embodiment.
Fig. 7 be in PBS buffering (10mM, pH=7.4) system, 5 μ g/mL carbon dots respectively the amino acid different from 200 μM,
200 μM of different ROS, 1mM anions and canons, the fluorescence spectrum that the fluorescence intensity after reaction at 546nm changes with time
Figure.
Fig. 8 is common location figure of 1 carbon dots of embodiment in healthy cell and dead cell.(A) it is healthy cell, is first incubated for carbon
Point 30 minutes is imaged after being incubated for business mitochondrial dye 30 minutes；(B) it is dead cell, is fixed carefully with 4% paraformaldehyde
Born of the same parents 30min, then it is incubated for carbon dots 30 minutes, it is incubated for business nucleus dyestuff and is imaged after 30 minutes.
Fig. 9 is common location figure of 1 carbon dots of embodiment in apoptotic cell.(A) group is first to be incubated for carbon dots and business lysosome
CCCP (20 μM) apoptosis is being added in probe；(B) group is first to be incubated for carbon dots and business lysosome probe, and H is being added2O2(8mM) withers
It dies；(C) group is first to be incubated for carbon dots and business lysosome probe, adds HBSS apoptosis.
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical solution of the present invention is clearly and completely described, it is clear that institute
The embodiment of description is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention,
Those of ordinary skill in the art's every other embodiment obtained under that premise of not paying creative labor, belongs to this hair
The range of bright protection.
Embodiment 1
The synthesis of carbon dots, steps are as follows:
By 2,4- 4-dihydroxy benzaldehyde and 1,2,3,3- tetramethyl -3H- iodate indoles are dissolved with molar ratio for the ratio of 3:1
In dehydrated alcohol, 130 DEG C microwave reaction 1 hour, purified after cooling with 0.22 μM of filter membrane, rotary evaporation obtains wine-colored
Carbon dots solid is dissolved in DMSO as stock solution.
Fig. 1 is the TEM map of carbon dots, and the structure of almost spherical, it is 1.7nm that partial size, which counts size, the crystalline substance of corresponding 0.23nm
Lattice illustrate to have formd carbon dots.
Fig. 2 is the IR map of carbon dots, 3428.11cm-1Corresponding to the stretching vibration of-OH, 3156.79cm-1Corresponding to-N-H
Stretching vibration, 1620.50,1578.45,1503.36,1477.81cm-1Corresponding to fragrant hydrogen, 1620.50cm-1Corresponding to C
The stretching vibration of=C/C=N, 1316.79cm-1Corresponding to the stretching vibration of C-N, 1263.19cm-1Flexible vibration corresponding to C-O
It is dynamic, 854.33,705.97cm-1Corresponding to C-H, the bending vibration of-OH.Illustrate that two kinds of raw materials have been combined together, generates
Carbon dots.
Fig. 3 is the XPS map of carbon dots, and 284.8,400.92 and 532.36eV corresponds respectively to C1s, N1s and O1s, they
Atomic percent be respectively 77.02%, 1.09% and 21.89%, further illustrate the generation of carbon dots.
Fig. 4 is carbon dots (5 μ g mL-1) ultraviolet and fluorescence spectra in PBS (10mM pH=7.4), maximum
It absorbs and transmitting is 525nm and 546nm respectively.
Fig. 5 is carbon dots in PBS (10mM pH=7.4), the fluorescence lifetime map at 546nm, and fluorescence lifetime is
1.0337ns。
Fig. 6 is photostability map of the carbon dots in PBS (10mM pH=7.4), the Continuous irradiation under 250W xenon lamp
30min, the fluorescence intensities of carbon dots illustrate that carbon dots anti-light can bleach there is no apparent variation occurs, suitable for biology at
Picture.
Embodiment 2
The reaction of the 5 μ g/mL carbon dots amino acid different from 200 μM, 200 μM of different ROS, 1mM zwitterions
In PBS buffering (10mM, pH=7.4) system containing 5 μ g/mL carbon dots of 2mL, it is separately added into 20 μ L 20mM's
Analyte: 1: carbon dots；2: threonine；3: arginine；4: methionine；5: proline；6: glycine；7: lysine；8: bright ammonia
Acid；9: tryptophan；10: isoleucine；11: alanine；12: histidine；13: glutamic acid；14: aspartic acid；15: valine；
16: serine；17: cysteine；18: homocysteine；19: glutathione；20:H2O2；21:NaNO2；22:t-BuOOH；
23:.OH；24:KCl；25:CaCl2；26:NaCl；27:MgCl2；28:AlCl3；29:ZnSO4；30:FeCl3；31:FeCl2；
32:CuSO4；33:NiCl2；34:CrCl3；35:K2CrO7；36:MnCl2；37:NaF；38:NaCl；39:NaBr；40:KI；41:
Na2SO4；42:Mg (NO3)2Carry out fluorescence spectrometry.Fluorescence intensity of the different analytes at 546nm is compared simultaneously
Compared with.Fig. 7 experimental data shows that carbon dots are not reacted with these analytes.
Embodiment 3
Common location of the carbon dots in different health status cells
Healthy cell: being added carbon dots (10 μ g/mL) in the cell culture medium of 1mL, cultivates 30min, washs three with PBS
It is secondary, business mitochondrial probe Mito Tracker Deep Red (100nM) is added and cultivates 30min, is washed three times with PBS, altogether
It is Chong Die with business mitochondrial probe very well that carbon dots can be observed in focusing microscope, illustrate that carbon dots can be with targetted mitochondria.
Apoptotic cell: being added carbon dots (10 μ g/mL) in the cell culture medium of 1mL, cultivates 30min, washs three with PBS
It is secondary, it is added business lysosome probe Lyso Tracker Deep Red (100nM), cultivates 30min, washed three times, added with PBS
It is Chong Die with business lysosome probe very poor that carbon dots can be observed in the cell culture medium for entering 1mL in Laser Scanning Confocal Microscope.Then plus
Entering carbonyl cyano 3- chlorobenzene hydrazone, (a kind of CCCP, film potential that can reduce mitochondrial inner membrane two sides, promotes the object of Apoptosis
Matter, 20 μM), can be observed in Laser Scanning Confocal Microscope, overlapping preferably, illustrates carbon dots in mitochondrial membrane potential after CCCP is added
It reduces, when Apoptosis can target lysosome.
Carbon dots (10 μ g/mL) is added in the cell culture medium of 1mL, cultivates 30min, is washed three times with PBS, business is added
Lysosome probe Lyso Tracker Deep Red (100nM) cultivates 30min, the cell that 1mL is added three times is washed with PBS
It is Chong Die with business lysosome probe very poor that carbon dots can be observed in Laser Scanning Confocal Microscope in culture medium.H is added2O2(8mM, Yi Zhongke
To inhibit oxidation-respiration chain, the substance of inducing cell damage), it can be observed in Laser Scanning Confocal Microscope, H be added2O2It is overlapped later
Preferably, illustrate that carbon dots can target lysosome in Apoptosis.
Carbon dots (10 μ g/mL) is added in the cell culture medium of 1mL, cultivates 30min, is washed three times with PBS, business is added
Lysosome probe Lyso Tracker Deep Red (100nM) cultivates 30min, the cell that 1mL is added three times is washed with PBS
It is Chong Die with business lysosome probe very poor that carbon dots can be observed in Laser Scanning Confocal Microscope in culture medium.Change 1mL starvation media into,
A kind of balanced salt solution (HBSS, substance by hungry Induces Autophagy) of hanks, is overlapped increasingly in 180 minutes
It is good, illustrate that carbon dots can target lysosome in Apoptosis.
Dead cell: the fixed cell 30min of paraformaldehyde of 1mL 4% is added in Tissue Culture Dish, washs three with PBS
It is secondary, carbon dots (10 μ g/mL) is added in the cell culture medium of 1mL, cultivates 30min, is washed three times with PBS, business cell is added
Nuclear probe DAPI (1 μ g/mL) cultivates 30min, washs the cell culture medium that 1mL is added three times with PBS, in Laser Scanning Confocal Microscope
It is Chong Die with business cell nuclear probe very well that carbon dots can be observed, illustrate that carbon dots can target nucleus in dead cell.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Within mind and principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (5)
1. a kind of preparation method for the fluorescent carbon point for detecting cell activity, it is characterised in that: by 2,4- 4-dihydroxy benzaldehyde and 1,
2,3,3- tetramethyl -3H- iodate indoles are dissolved in dehydrated alcohol, microwave reaction 1h, are purified after cooling with filter membrane, rotary evaporation
Obtain wine-colored carbon dots solid.
2. the preparation method of the fluorescent carbon point of detection cell activity according to claim 1, it is characterised in that: described 2,4-
4-dihydroxy benzaldehyde and 1, the molar ratio of 2,3,3- tetramethyl -3H- iodate indoles are 3:1.
3. the preparation method of the fluorescent carbon point of detection cell activity according to claim 2, it is characterised in that: the microwave
Reaction temperature is 130 DEG C, is purified after cooling with 0.22 μM of filter membrane.
4. the fluorescent carbon point of claim 1-3 described in any item preparation methods preparation, it is characterised in that: the fluorescent carbon point is
Detect the fluorescent carbon point of cell activity.
5. the application of fluorescent carbon point as claimed in claim 4, it is characterised in that: the fluorescent carbon point passes through in different organelles
Positioning realize monitoring mitochondrial membrane potential, distinguish health, apoptosis and dead cell.
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| CN111072011A (en) * | 2020-01-15 | 2020-04-28 | 郑州大学 | Preparation of mitochondria-nucleolus reversible migration fluorescent carbon dot and application of mitochondria-nucleolus reversible migration fluorescent carbon dot in monitoring cell activity |
| CN115948163A (en) * | 2023-01-03 | 2023-04-11 | 扬州工业职业技术学院 | Near-infrared fluorescent probe for selectively recognizing glutathione |
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