CN109280017A - A kind of two-photon fluorescence Golgi localization agent and its preparation method and application - Google Patents
A kind of two-photon fluorescence Golgi localization agent and its preparation method and application Download PDFInfo
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Abstract
The invention discloses a kind of two-photon fluorescence Golgi localization agent and its preparation method and application, belong to technical field of analytical chemistry.Technical solution of the present invention main points are as follows: a kind of two-photon fluorescence Golgi localization agent, structural formula are as follows:Application the invention also discloses the preparation method of the two-photon fluorescence Golgi localization agent and its in apoptosis process in the imaging research of golgiosome cracking process in terms of the tracer of golgiosome label.Targeting agent of the invention has preferable golgiosome targeting ability, higher two photon absorption cross section and good photostability, and cytotoxicity is lower.
Description
Technical field
The present invention relates to a kind of two-photon fluorescence Golgi localization agent and its preparation method and application, belong to analytical chemistry
Technical field.
Background technique
Cell is the basic structure and functional unit of organism, and organelle is the indispensable a part of cell.Eukaryon
There are various organelles, including mitochondria, lysosome, endosome, endoplasmic reticulum, golgiosome etc. in cell, they maintain cell
Normal function.The real-time tracking organelle on subcellsular level, can property that is more acurrate, gaining more insight into organelle and
Its complicated biological function and process.Golgiosome is mainly made of the membrane vesicle for stacking and flattening, and is related to protein
Modification, sorting and packaging, and secreted and be delivered to other organelles or be secreted into extracellular.Currently, golgiosome is permitted
More CONSTRUCTED SPECIFICATIONs and function are still unknown.In addition, it is some research shows that golgiosome is related with disease, such as cancer, skin
Skin relaxation and cystic fibrosis etc..Therefore, the form to golgiosome in complicated physiology and pathologic process is moved in real time
The tracer of state is particularly important.
In recent years, due to Imaging-PAM high sensitivity, high spatial resolution, quickly analysis and not damaged sample preparation
Advantage, it is for thin that the Imaging-PAM based on small organic molecule, which has been widely used for observation cellular morphology and structure,
The powerful of born of the same parents' research, can satisfy the needs in subcellsular level organelle real time imagery.Up to the present, based on having
The research of the subcellsular level organelle-specificity fluorescent tracer of machine small molecule has had significant progress.However, these
Research focuses primarily upon mitochondria, lysosome, nucleus, and the report of the fluorescent tracer of golgiosome is less.
Currently, including electron microscope, single photon fluorescence dyestuff and golgiosome target with golgiosome targeting proteins
The real-time tracer of golgiosome is developed to fluorescent fusion protein.However, electron microscope is not suitable for Gorky
Dynamic tracing of the body in living cells.And for latter three kinds, they are all using single photon fluorescence imaging technique, it is difficult to avoid light
The disadvantages of bleaching phenomenon, biology intracorporal autofluorescence interference and bio-imaging depth are shallower.Two-photon fluorescence imaging technology
(TPM) excitaton source is used as using near-infrared laser pulse, with lesser background fluorescence, deeper imaging penetration depth, higher
Spatial resolution and the advantages that longer observing time, this is imaged more suitable for the organelle of subcellsular level.However, being used for
The report of the two-photon fluorescence tracer of golgiosome is still less.
Summary of the invention
Problem encountered is imaged for current golgiosome fluorescent tracing, it is high that the present invention provides a kind of two-photon fluorescences
Dictyosome targeting agent, the targeting agent have preferable golgiosome targeting ability, higher two photon absorption cross section and good
Photostability, and cytotoxicity is lower.
The present invention also provides a kind of preparation method of two-photon fluorescence Golgi localization agent and its in Apoptosis mistake
Application in journey in the imaging research of golgiosome cracking process in terms of the tracer of golgiosome label.
The present invention adopts the following technical scheme that solve above-mentioned technical problem, a kind of two-photon fluorescence Golgi localization
Agent, it is characterised in that the structural formula of the targeting agent is as follows:
The preparation method of two-photon fluorescence Golgi localization agent of the present invention, it is characterised in that specific steps are as follows:
Step S1: by 10g 1- (6- methoxyl group -2- naphthalene) -1- ethyl ketone, 80mL concentrated hydrochloric acid, 2mL methylene chloride and
0.75mL triethylamine is added into the three neck round bottom of 100mL, 110 DEG C of reaction 2h is heated with stirring to, by reaction solution after cooling
Yellow solid precipitate is obtained by filtration, then precipitating is dissolved in 20mL ethyl acetate, with saturated common salt water washing, uses anhydrous slufuric acid
Magnesium is dry, then removes solvent under reduced pressure and obtains crude product, crude product is dissolved in NaOH solution, molten in 0 DEG C of addition hydrochloric acid
Liquid is formed completely up to yellow mercury oxide, filters out pure compound 1, structural formula is as follows:
Step S2: by 1g compound 1,30mL H2O、2g Na2S2O5The methylamine water solution for being 40% with 0.8g mass concentration
It is added into the glass heavy wall pressure pipe of 50mL, is heated to 140 DEG C of reaction 4h under microwave condition, reaction unit is cooled to room
Reaction mixture is filtered after temperature and is washed to obtain greenish yellow solid crude product with a large amount of cold water, then by gained crude product through volume
Than the CHCl for 3:13/ EtOH is recrystallized to give pure compound 2, and structural formula is as follows:
Step S3: by 3.0g compound 2,50mL acetonitrile, 2.0g methyl bromoacetate, 1.9g disodium hydrogen phosphate and 0.5g iodate
Sodium is added into the round-bottomed flask of 100mL, and in 81 DEG C of reaction 4h, reaction solution is cooled to room temperature, successively be added 50mL water and
50mL ethyl acetate, extraction and separation recycle organic phase, organic phase are washed, then is washed with saturated common salt, is then removed under reduced pressure
It goes solvent to obtain crude product, then gained crude product is purified to obtain compound 3 through ethyl alcohol recrystallization, structural formula is as follows:
Step S4: 2.0g compound 3,0.70g potassium hydroxide and 50mL ethyl alcohol are added into the round-bottomed flask of 100mL,
Reaction 5h is stirred at room temperature, then the dilution of 100mL mixture of ice and water is added into reaction solution, is then acidified to pH=3 with concentrated hydrochloric acid,
Precipitating is precipitated, then filters out precipitating, is washed with distilled water, then obtains compound 4 with chloroform/petroleum ether recrystallization purification,
Structural formula is as follows:
Step S5: by 128mg compound 4,265mg BOP, 20mL CH2Cl2, 5mL DMF and 0.1mL N, N- diisopropyl
Base ethamine is added into the round-bottomed flask of 50mL, be stirred at room temperature reaction 1h, then into round-bottomed flask be added dropwise 5mL dissolved with
The dichloromethane solution of 165mg sphingol, and continue to be stirred to react 5h in room temperature, it is separated after solvent is removed under reduced pressure with silica gel column chromatography
Obtain target compound TP-G.
Two-photon fluorescence Golgi localization agent golgiosome cracking process in apoptosis process of the present invention
Imaging research in application in terms of golgiosome label tracer, the intracellular golgiosome two-photon fluorescence imaging of the targeting agent grinds
Study carefully, specifically includes the two-photon fluorescence tracer monitoring that spectral property is investigated, golgiosome common location is tested, golgiosome cracks.
Compared with the prior art, the invention has the following beneficial effects: the synthesis of (1) targeting agent is easier, and rear place
Reason process is relatively easy；(2) targeting agent can be applied to label and the tracer of cell golgiosome, by GES-1,
It is compared in these three cells of HepG2, MCF-7 with commercialization Golgi localization agent, it is found that it is preferable this targeting agent has
Golgiosome targets ability, and the common location coefficient of two kinds of targeting agents is all larger than 0.9, illustrates that this targeting agent can be used as cell Gao Er
The targeting agent of matrix；(3) targeting agent has biggish two photon absorption cross section, can be used for the two-photon fluorescence of golgiosome at
Light injury, raising tissue as label and tracer, by autofluorescence background interference, reduction in reduction life entity to biological sample
The features such as penetration depth, to obtain more accurate and stable optical signalling and imaging effect.So the targeting agent in the present invention
It marks in golgiosome and has broad application prospects with tracer field, to golgiosome in organism physiology and pathologic process
The research of mechanism of action is of great significance.
Detailed description of the invention
Fig. 1 is normalization ultraviolet-visible absorption spectroscopy of the targeting agent TP-G made from embodiment 1 in opposed polarity solvent
Figure；
Fig. 2 is normalization fluorescence emission spectrogram of compound of the targeting agent TP-G made from embodiment 1 in opposed polarity solvent；
Fig. 3 is the Two-photon excitation spectra figure of targeting agent TP-G made from embodiment 1 in ethanol；
Fig. 4 is targeting agent TP-G made from embodiment 1 high with commercialization in these three cells of GES-1, HepG2, HepG2
The common location image of dictyosome targeting agent Golgi-Tracker Red, wherein a) targeting agent concentration is 1 μM and Golgi-
Tracker Red (5 μM) is added to the single photon fluorescence imaging contexts in GES-1 cell, b) targeting agent concentration be 1 μM with
Golgi-Tracker Red (5 μM) is added to the single photon fluorescence imaging contexts in HepG2 cell, c) targeting agent concentration be 1 μM
The single photon fluorescence imaging contexts in HepG2 cell are added to Golgi-Tracker Red (5 μM)；
Fig. 5 is that targeting agent TP-G made from embodiment 1 (1 μM) two-photon excitation photostability in HeLa investigates result
Figure, wherein two-photon excitation wavelength is 750nm；
Fig. 6 be targeting agent TP-G made from embodiment 1 (1 μM) under two-photon fluorescence imaging mode in real time to star spore bacterium
The monitoring and tracer of golgiosome cracking process in the HeLa apoptosis process of (2 μM) inductions of element, it is wherein a) fixed to be only added
The golgiosome fluorescence imaging figure of position agent TP-G (1 μM), b) and c) be that targeting agent TP-G (1 μM) and staurosporin (2 μ are added
M) the golgiosome fluorescence imaging figure in different cracking degree after 4h.
Specific embodiment
Above content of the invention is described in further details by the following examples, but this should not be interpreted as to this
The range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on above content of the present invention belong to this hair
Bright range.
Embodiment 1
The synthesis of targeting agent TP-G
(1) synthesis of compound 1
(about by 10g 1- (6- methoxyl group -2- naphthalene) -1- ethyl ketone, 80mL concentrated hydrochloric acid, 2mL methylene chloride and 15 drops
0.75mL) triethylamine is added into the three neck round bottom of 100mL, 110 DEG C of reaction 2h is heated with stirring to, by reaction solution after cooling
Yellow solid precipitate is obtained by filtration, precipitating is dissolved in 20mL ethyl acetate, with saturated common salt water washing (50mL × 3), uses
Anhydrous magnesium sulfate is dry, then removes solvent under reduced pressure and obtains crude product, crude product is dissolved in the NaOH solution of 1mol/L,
In 0 DEG C be added 1mol/L hydrochloric acid solution until yellow mercury oxide formed completely, filter out pure compound 1, dry to obtain 8.09g, production
Rate 81%, synthetic route is as follows:
(2) synthesis of compound 2
By 1g compound 1,30mL H2O、2g Na2S2O5With 0.8g mass concentration be 40% methylamine water solution be added to
In the glass heavy wall pressure pipe of 50mL, it is heated to 140 DEG C of reaction 4h under microwave condition, reaction unit is cooled to will after room temperature
Reaction mixture filtering simultaneously washs to obtain greenish yellow solid crude product with a large amount of cold water, then by gained crude product through volume ratio is 3:
1 CHCl3/ EtOH is recrystallized to give pure compound 2, is light yellow crystal, 0.67g, yield 67%, synthetic route is as follows:
(3) synthesis of compound 3
3.0g compound 2,50mL acetonitrile, 2.0g methyl bromoacetate, 1.9g disodium hydrogen phosphate and 0.5g sodium iodide are added
Into the round-bottomed flask of 100mL, in 81 DEG C of reaction 4h, reaction solution is cooled to room temperature, 50mL water and 50mL acetic acid is successively added
Organic phase is recycled in ethyl ester, extraction and separation, and organic phase is washed (50mL × 2), then washes (50mL × 1) with saturated common salt, so
It removes solvent under reduced pressure afterwards and obtains crude product, then obtained crude product through ethyl alcohol recrystallization purified to obtain compound faint yellow
Powder compounds 3,2.5g, yield 70%, synthetic route is as follows:
(4) synthesis of compound 4
2.0g compound 3,0.70g potassium hydroxide and 50mL ethyl alcohol are added into the round-bottomed flask of 100mL, stirred in room temperature
Reaction 5h is mixed, the dilution of 100mL ice water is added into reaction solution, is then slowly acidified to pH=3 with concentrated hydrochloric acid, precipitating is precipitated, with
After filter out precipitating, be washed with distilled water, then obtain dark yellow solid compound 4 with the recrystallization purification of chloroform/petroleum ether,
1.5g, yield 63%, synthetic route is as follows:
(5) synthesis of targeting agent TP-G
By 128mg compound 4,265mg BOP, 20mL CH2Cl2, 5mL DMF and 0.1mL N, N- diisopropylethylamine adds
Enter into the round-bottomed flask of 50mL, be stirred to react 1h at room temperature, 5mL is then added dropwise into flask dissolved with the two of 165mg sphingol
Chloromethane solution, and continue to be stirred to react 5h at room temperature, after solvent is removed under reduced pressure, residue uses CH by silica gel chromatograph2Cl2/
MeOH (25:1, v/v) obtains compound TP-G as eluent, is bright yellow solid, 102mg, yield 19%.1H NMR
(DMSO-d6,400MHz) δ (ppm): 8.446-8.444 (d, J=0.8Hz, 1H), 7.895-7.872 (d, J=9.2Hz, 1H),
7.828-7.802 (dd, J=1.6Hz&J=8.8Hz, 1H), 7.662-7.599 (m, 2H), 7.194-7.165 (dd, J=
2.4Hz&J=9.2Hz, 1H), 6.944-6.938 (d, J=2.4Hz, 1H), 5.545-5.474 (m, 1H), 5.393-5.338
(dd, J=6.4Hz&J=15.6Hz, 1H), 4.868-4,855 (d, J=5.2Hz, 1H), 4.596-4.569 (t, J=
5.48Hz, 1H), 4.117-4.026 (m, 2H), 3.959-3.912 (dd, J=6.4Hz&J=12.4Hz, 1H), 3.713-
3.648(m,1H),3.551-3.428(m,2H),3.107(s,3H),2.611(s,3H),1.857-1.807(m,2H),
1.276-1.159 (m, 22H), 0.861-0.827 (t, J=7.2Hz, 3H) .MS (ESI): m/z561.3651for [M+Na]+,
Synthetic route is as follows:
Embodiment 2
The measurement of normalization ultraviolet-visible absorption spectroscopy figure of the targeting agent TP-G in opposed polarity solvent
Targeting agent TP-G prepared by Example 1 is dissolved in methylene chloride, n,N-Dimethylformamide, in ethyl alcohol, eventually respectively
Concentration is 10 μM.The instrument of ultraviolet-visible absorption spectroscopy measurement is TU-1900 type ultraviolet-uisible spectrophotometer
(Beijing Purkinje General Instrument Co.,Ltd.).As can be known from Fig. 1, with the increasing of solvent polarity
Add, the gradually red shift of the absorbing wavelength of targeting agent TP-G.
Embodiment 3
The measurement of normalization fluorescence spectra of the targeting agent TP-G in opposed polarity solvent
Fig. 2 is normalization fluorescence spectra of the targeting agent TP-G in opposed polarity solvent.From figure 2 as can be seen that with
The increase of solvent polarity, the gradually red shift of the fluorescence emission wavelengths of targeting agent TP-G.Fluoremetry instrument used is Perkin
Elmer LS55 sepectrophotofluorometer, the excitation wavelength of measurement are targeting agent TP-G absorption maximum in three kinds of solvents in Fig. 1
Wavelength, slit width are set as 5nm/5nm.
Embodiment 4
The measurement of the Two-photon excitation spectra figure of targeting agent TP-G in ethanol
Using fluorescein as object of reference, within the scope of 720-860nm in ethanol at interval of 20nm measurement and positioning agent TP-G
Two-photon fluorescence excitation emission spectrum calculates the two photon absorption cross section at each wavelength using obtained spectrum, according to absorption
Cross-section data further draws Two-photon excitation spectra figure (as shown in Figure 3).Emit light according to the two-photon fluorescence excitation measured
Spectrum, utilizes formula δ=δr(SsΦrφrcr)/(SrΦsφscs) two photon absorption cross section is calculated, wherein subscript s and r are respectively indicated
Sample and reference molecule.The intensity for the signal that ccd detector is collected into is expressed as area S, and Φ is fluorescence quantum yield, and φ is real
The overall fluorescent collection efficiency of experiment device.The concentration that agent molecule is positioned in solution is expressed as c.δrIt is the double of reference molecule fluorescein
Photon absorption cross sections value.Fluorescence quantum yield, reference substance DMSO are calculated by measuring the emission spectrum integral area of TP-G
Middle coumarin-1 (Φ=0.58) compares as the measured value of reference compound.Fluorescence quantum yield uses Φs=Φr
(ArFs/AsFr)(ηs/ηr)2It calculates, wherein wherein subscript s and r respectively indicates sample and reference molecule, Φ is that fluorescent quantum produces
Rate, F are the areas of fluorescent emission, and η is the refractive index of solvent, and A is the absorbance of standard items and sample in excitation wave strong point.
Embodiment 5
In these three cells of GES-1, HepG2, HepG2, by targeting agent TP-G and commercialization Golgi localization agent
Golgi-Tracker Red carries out common location experiment, illustrates that targeting agent TP-G can be navigated in golgiosome (such as Fig. 4 institute
Show).Concrete operation step is following (by taking GES-1 cell as an example): by the DMSO solution of targeting agent TP-G and commercialization golgiosome
Targeting agent Golgi-Tracker Red is added in the culture solution for giving birth to GES-1 cell, and the two final concentration is respectively 1 μM and 5 μ
M.It is imaged after cultivating 30min in carbon dioxide incubator with Laser Scanning Confocal Microscope, while being excited with 405nm and 543nm,
In green channel it can be observed that there is green fluorescence (460-540nm) sending, this is the light of targeting agent TP-G transmitting, and in red
Channel has been observed that red fluorescence (600-640nm) is issued, this is issued for probe targeting agent Golgi-Tracker Red
Feux rouges is handled the two it can be concluded that the common location coefficient of two kinds of dyestuffs is 0.94 with software.In HepG2, HepG2 cell
Common location experimental implementation is same as above, and common location coefficient is respectively 0.97 and 0.95.
Embodiment 6
The two-photon excitation photostability of targeting agent TP-G is investigated
In HeLa cell, targeting agent TP-G two-photon excitation photostability is investigated.Specific steps are as follows: will positioning
The DMSO solution of agent TP-G is added in the culture solution for giving birth to HeLa cell, and final concentration of 1 μM.It is trained in carbon dioxide incubator
After supporting 30min, under two photon imaging mode, with 750nm excitation wavelength, exciting power is the 6% of maximum power, lasting to be imaged
15min.Targeting agent TP-G has preferable photostability as can be known from Fig. 5, still remains initial fluorescent intensity after 8min is imaged
50% intensity.
Embodiment 7
The cracking of golgiosome in targeting agent TP-G real-time imaging apoptosis process
In HeLa cell, under two photon imaging mode, using targeting agent TP-G to golgiosome in apoptosis process
Cracking carry out real-time imaging monitoring with tracer (as shown in Figure 6).Specific steps are as follows: the DMSO of targeting agent TP-G is molten
Liquid is added in the culture solution for giving birth to HeLa cell, and final concentration is 1 μM.After cultivating 30min in carbon dioxide incubator,
Under two photon imaging mode, with 750nm excitation wavelength, two groups of cells are imaged.It is found that cell is normally given birth to from Fig. 6 a
Long, golgiosome pattern is good, the green fluorescence spot of only one aggregation inside most cells.Then, continue to thin
(2 μM) culture 4h of cell death inducer staurosporin are added in born of the same parents' culture solution, are then imaged under two-photon mode.From figure
6b and Fig. 6 c it is found that the cell of staurosporin addition induction of HeLa cell apoptosis (inferring from light field figure), while it is every
The single green fluorescence spot of a intracellular script aggregation, gradually cracks or is dispersed into multiple green spots, this result table
Bright targeting agent TP-G successfully realizes the tracer of the cracking of golgiosome in apoptosis process, has certain practical application
Value.
Embodiment above describes basic principles and main features of the invention and advantage, the technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (3)
1. a kind of two-photon fluorescence Golgi localization agent, it is characterised in that the structural formula of the targeting agent is as follows:
2. a kind of preparation method of two-photon fluorescence Golgi localization agent described in claim 1, it is characterised in that specific step
Suddenly are as follows:
Step S1: by 10g 1- (6- methoxyl group -2- naphthalene) -1- ethyl ketone, 80mL concentrated hydrochloric acid, 2mL methylene chloride and 0.75mL tri-
Ethamine is added into the three neck round bottom of 100mL, is heated with stirring to 110 DEG C of reaction 2h, reaction solution is obtained by filtration after cooling
Yellow solid precipitate, then precipitating is dissolved in 20mL ethyl acetate, it is dry with anhydrous magnesium sulfate with saturated common salt water washing,
Then solvent is removed under reduced pressure and obtains crude product, and crude product is dissolved in NaOH solution, it is in 0 DEG C of addition hydrochloric acid solution until yellow
Color precipitates to be formed completely, filters out pure compound 1, structural formula is as follows:
Step S2: by 1g compound 1,30mL H2O、2g Na2S2O5The methylamine water solution for being 40% with 0.8g mass concentration is added
Into the glass heavy wall pressure pipe of 50mL, it is heated to 140 DEG C of reaction 4h under microwave condition, after reaction unit is cooled to room temperature
Reaction mixture is filtered and is washed to obtain greenish yellow solid crude product with a large amount of cold water, then is through volume ratio by gained crude product
The CHCl of 3:13/ EtOH is recrystallized to give pure compound 2, and structural formula is as follows:
Step S3: 3.0g compound 2,50mL acetonitrile, 2.0g methyl bromoacetate, 1.9g disodium hydrogen phosphate and 0.5g sodium iodide are added
Enter into the round-bottomed flask of 100mL, in 81 DEG C of reaction 4h, reaction solution is cooled to room temperature, 50mL water and 50mL second is successively added
Acetoacetic ester, extraction and separation recycle organic phase, organic phase are washed, then is washed with saturated common salt, then removes solvent under reduced pressure
Crude product is obtained, then gained crude product is purified to obtain compound 3 through ethyl alcohol recrystallization, structural formula is as follows:
Step S4: 2.0g compound 3,0.7g potassium hydroxide and 50mL ethyl alcohol are added into the round-bottomed flask of 100mL, in room temperature
It is stirred to react 5h, then the dilution of 100mL mixture of ice and water is added into reaction solution, is then acidified to pH=3 with concentrated hydrochloric acid, it is heavy to be precipitated
It forms sediment, then filters out precipitating, be washed with distilled water, then obtain compound 4, structural formula with chloroform/petroleum ether recrystallization purification
It is as follows:
Step S5: by 128mg compound 4,265mg BOP, 20mL CH2Cl2, 5mL DMF and 0.1mL N, N- diisopropyl second
Amine is added into the round-bottomed flask of 50mL, and reaction 1h is stirred at room temperature, and 5mL is then added dropwise into round-bottomed flask dissolved with 165mg sheath
The dichloromethane solution of ammonia alcohol, and continue to be stirred to react 5h in room temperature, the isolated mesh of silica gel column chromatography is used after solvent is removed under reduced pressure
Mark compound TP-G.
3. two-photon fluorescence Golgi localization agent golgiosome cracking process in apoptosis process described in claim 1
Imaging research in application in terms of golgiosome label tracer, the intracellular golgiosome two-photon fluorescence imaging of the targeting agent grinds
Study carefully, specifically includes the two-photon fluorescence tracer monitoring that spectral property is investigated, golgiosome common location is tested, golgiosome cracks.
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| CN110514637A (en) * | 2019-10-10 | 2019-11-29 | 温州医科大学附属第一医院 | It is a kind of with mano-porous material be enhance matrix fluorescence spectrum drug test method |
| CN111039866A (en) * | 2019-12-16 | 2020-04-21 | 济南大学 | Golgi-targeted hydrogen sulfide fluorescent probe, and preparation method and application thereof |
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| CN104529893A (en) * | 2014-12-30 | 2015-04-22 | 中国科学技术大学 | Novel quinoline dye capable of being used as Golgi apparatus organelle probe |
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| CN110514637A (en) * | 2019-10-10 | 2019-11-29 | 温州医科大学附属第一医院 | It is a kind of with mano-porous material be enhance matrix fluorescence spectrum drug test method |
| CN111039866A (en) * | 2019-12-16 | 2020-04-21 | 济南大学 | Golgi-targeted hydrogen sulfide fluorescent probe, and preparation method and application thereof |
| CN111039866B (en) * | 2019-12-16 | 2022-02-25 | 济南大学 | Golgi-targeted hydrogen sulfide fluorescent probe, and preparation method and application thereof |
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