CN107955606A - A kind of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes and preparation method thereof - Google Patents
A kind of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes and preparation method thereof Download PDFInfo
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- 238000003384 imaging method Methods 0.000 title claims abstract description 38
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 239000000523 sample Substances 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 229910052769 Ytterbium Inorganic materials 0.000 claims abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229910052688 Gadolinium Inorganic materials 0.000 claims abstract description 17
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 claims abstract description 17
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims abstract description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
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- 238000000034 method Methods 0.000 claims abstract 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 229910003317 GdCl3 Inorganic materials 0.000 claims description 10
- 239000006228 supernatant Substances 0.000 claims description 10
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 7
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 7
- 229930064664 L-arginine Natural products 0.000 claims description 7
- 235000014852 L-arginine Nutrition 0.000 claims description 7
- 238000005119 centrifugation Methods 0.000 claims description 7
- 238000000502 dialysis Methods 0.000 claims description 7
- MEANOSLIBWSCIT-UHFFFAOYSA-K gadolinium trichloride Chemical compound Cl[Gd](Cl)Cl MEANOSLIBWSCIT-UHFFFAOYSA-K 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
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- 238000006243 chemical reaction Methods 0.000 claims description 3
- KBQHZAAAGSGFKK-UHFFFAOYSA-N dysprosium atom Chemical compound [Dy] KBQHZAAAGSGFKK-UHFFFAOYSA-N 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 claims description 3
- 238000001471 micro-filtration Methods 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims 1
- 238000002595 magnetic resonance imaging Methods 0.000 abstract description 9
- 238000013170 computed tomography imaging Methods 0.000 abstract description 6
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- 239000000126 substance Substances 0.000 abstract description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 abstract 1
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- YLPBXIKWXNRACS-UHFFFAOYSA-N iobitridol Chemical compound OCC(O)CN(C)C(=O)C1=C(I)C(NC(=O)C(CO)CO)=C(I)C(C(=O)N(C)CC(O)CO)=C1I YLPBXIKWXNRACS-UHFFFAOYSA-N 0.000 description 5
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- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
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- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
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- 125000000524 functional group Chemical group 0.000 description 1
- LGMLJQFQKXPRGA-VPVMAENOSA-K gadopentetate dimeglumine Chemical compound [Gd+3].CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O LGMLJQFQKXPRGA-VPVMAENOSA-K 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
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- 229910021645 metal ion Inorganic materials 0.000 description 1
- 231100000783 metal toxicity Toxicity 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 description 1
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 229960003110 quinine sulfate Drugs 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- CKLHRQNQYIJFFX-UHFFFAOYSA-K ytterbium(III) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Yb+3] CKLHRQNQYIJFFX-UHFFFAOYSA-K 0.000 description 1
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- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
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Abstract
The object of the present invention is to provide a kind of new double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes and preparation method thereof, belong to medical image technical field of material.The gadolinium and ytterbium codope carbon dots, expression formula that double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes of the present invention are made of carbon, nitrogen, oxygen, gadolinium and ytterbium element are Gd/Yb@CDs.The present invention also provides the preparation method of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes, this method preparation flow is simple, and obtained nano-probe need not be modified further, and longitudinal relaxation efficiency can reach 6.65mM‑1s‑1.Double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imagings probe of the present invention, which is suitable for magnetic resonance imaging, CT imagings and fluorescence imaging, longitudinal relaxation efficiency, can reach 6.65mM‑1s‑1, higher than the Gd DTPA (3.69mM of Clinical practice‑ 1s‑1);Compared with Gd@CDs, CT imaging functions are not only increased, and longitudinal relaxation efficiency is Gd@CDs (5.88mM‑1s‑1) 1.13 times;And there is higher chemical stability and relatively low toxicity.
Description
Technical field
The invention belongs to medical image technical field of material, and in particular to and a kind of double rear-earth-doped carbon dots magnetic resonance/
CT/ fluorescence multi-modality imaging probes and preparation method thereof.
Background technology
Mr imaging technique is because to human body is noninvasive, any direction tomoscan 3-D view and resolution ratio are higher, provides
Outstanding advantages of two aspect diagnostic evaluation of form and function, become clinically one of important means for medical diagnosis on disease.Face
Resolution ratio and the sensitivity of imaging can be improved using magnetic resonance contrast agent on bed, improves picture quality, enhancing contrast and can
The property read.But various imaging techniques have respective advantage and defect since realization principle is different, by the single diagnosis of tradition
Pattern can not provide the comprehensive information of disease, thus can be subject to certain restrictions when being diagnosed to various complex diseases.Cause
This, magnetic resonance imaging and other imaging techniques such as CT imagings, fluorescence imaging, ultrasonic imaging etc. are joined together to use, then can be with
Reach the effect of mutual supplement with each other's advantages, faster accurate information can be provided for the clinical diagnosis of disease, while can be by magnetic resonance imaging
It is combined together with various therapeutic modalities, that is, develops the diagnoses and treatment integration reagent based on magnetic resonance imaging, realizes to disease
The timely treatment of disease and real time monitoring.
The content of the invention
The object of the present invention is to provide a kind of new double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging to visit
Pin and preparation method thereof, the probe are a kind of Gd/Yb@CDs nano-probes suitable for MRI/CT/FI multi-modal imagings, it is vertical
It can reach 6.65mM to relaxivity-1s-1, higher than the Gd-DTPA (3.69mM of Clinical practice-1s-1), it is the Gd@reported
CDs(5.88mM-1s-1) 1.13 times.
To achieve these goals, technical scheme is specific as follows:
A kind of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes, are by carbon, nitrogen, oxygen, gadolinium and ytterbium member
The gadolinium and ytterbium codope carbon dots, expression formula of element composition are Gd/Yb@CDs.
In the above-mentioned technical solutions, the ytterbium element may be replaced by dysprosium or holmium element.
In the above-mentioned technical solutions, double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imagings probes are in single point
Scattered spherical, average grain diameter is 5.26 ± 0.93nm.
In the above-mentioned technical solutions, the percentage composition of the carbon, nitrogen, oxygen, gadolinium and ytterbium element be respectively 30.35%,
8.67%th, 32.20%, 7.40% and 21.38%.
A kind of preparation method of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes, including following step
Suddenly:
Step 1, by Na2EDTA、GdCl3、YbCl3It is dissolved in deionized water, magnetic agitation, obtains colourless with L-arginine
Transparent solution;
Step 2, the solution for the water white transparency for obtaining step 1 are transferred in reaction kettle, are reacted 10h at 200 DEG C, are treated it
After being cooled to room temperature, by the way that supernatant is collected by centrifugation;
Step 3, the supernatant for obtaining step 2 are transferred in dialysis membrane, and are dialysed with ultra-pure water;
Step 4, will obtain Gd/Yb@CDs after the solution micro-filtrate membrane filtration after dialysis, freeze-drying.
In the above-mentioned technical solutions, the GdCl3It may be replaced by DyCl3Or HoCl3。
In the above-mentioned technical solutions, the Na2EDTA、GdCl3、YbCl3Molar ratio with L-arginine is 250.00:
3.34:30.06:70.00。
In the above-mentioned technical solutions, the time of magnetic agitation is 15min in step 1.
In the above-mentioned technical solutions, rotating speed when supernatant being collected by centrifugation in step 2 is 11000rpm, time 20min.
In the above-mentioned technical solutions, the aperture of microfiltration membranes described in step 4 is 0.22 μm.
The beneficial effects of the invention are as follows:
Double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes provided by the invention are by carbon, nitrogen, oxygen, gadolinium
With the gadolinium and ytterbium codope carbon dots of ytterbium element composition, which is suitable for magnetic resonance imaging, CT imagings and fluorescence imaging, longitudinal direction and relaxes
Henan efficiency can reach 6.65mM-1s-1, higher than the Gd-DTPA (3.69mM of Clinical practice-1s-1)。
Double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes provided by the invention are compared with Gd@CDs, no
CT imaging functions are increase only, its longitudinal relaxation efficiency is also the Gd@CDs (5.88mM reported-1s-1) 1.13 times.
Gd, Yb in double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes provided by the invention will not be let out
Dew.
Double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imagings probes provided by the invention have higher chemistry
Stability and relatively low toxicity.
Double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes provided by the invention are imaged in MRI/CT/FI
It is middle as local contrast enhancing probe there is very big application potential.
The preparation method of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes provided by the invention, it is made
Standby flow is simple, and obtained nano-probe need not be modified further, its longitudinal relaxation efficiency can reach 6.65mM-1s-1。
Brief description of the drawings
The present invention is described in further detail with reference to the accompanying drawings and detailed description.
Fig. 1 is the HRTEM photos of Gd/Yb@CDs nano-particles prepared by the embodiment of the present invention.
Fig. 2 is the XPS spectrum figure of Gd/Yb@CDs nano-particles prepared by the embodiment of the present invention.
Fig. 3 is the FTIR spectrograms of Gd/Yb@CDs nano-particles prepared by the embodiment of the present invention.
Fig. 4 is Gd in Gd/Yb@CDs nano-particles prepared by the embodiment of the present invention3+Leak case chart.
Fig. 5 is that HeLa cells and the Gd/Yb@CDs of 4T1 cells and various concentrations are incubated the cell after 4h and 24h and deposit jointly
Motility rate.
Fig. 6 be the embodiment of the present invention prepare Gd/Yb@CDs UV-Vis spectrogram, wherein Fig. 6 A for absorption spectrum,
Fig. 6 B are excitation/emission fluorescence spectrum.
Fig. 7 is that HeLa cells and Gd/Yb@CDs (1mg/mL) are incubated the cell image after 2h jointly, wherein (A) is bright field
Image;(B) it is fluoroscopic image.
Fig. 8 is Gd/Yb@CDs nano-particles prepared by the embodiment of the present invention of various concentrations and the external MRI of Gd-DTPA
Imaging.
Fig. 9 is Gd/Yb@CDs nano-particles prepared by the embodiment of the present invention and the longitudinal relaxation efficiency 1/T of Gd-DTPA1With
The linear relationship chart of contrast medium concentration change.
Figure 10 be various concentrations the embodiment of the present invention prepare Gd/Yb@CDs nano-particles and iobitridol solution it is external
CT is imaged.
The Gd/Yb@CDs nano-particles and the CT values of iobitridol solution that Figure 11 is prepared for the embodiment of the present invention are with nano-particle
The linear relationship chart of concentration change.
Embodiment
The present invention is described in detail below in conjunction with the accompanying drawings.
Double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes provided by the invention, be by carbon, nitrogen, oxygen,
The gadolinium and ytterbium codope carbon dots, expression formula of gadolinium and ytterbium element composition are Gd/Yb@CDs, and in monodisperse spherical, average grain diameter is
5.26±0.93nm.Ytterbium element therein may be replaced by dysprosium or holmium element.It is preferred that the carbon, nitrogen, oxygen, gadolinium and ytterbium element
Percentage composition is respectively 30.35%, 8.67%, 32.20%, 7.40% and 21.38%.
The preparation method of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes provided by the invention, including
Following steps:
Step 1, by Na2EDTA、GdCl3、YbCl3It is dissolved in L-arginine in deionized water, magnetic agitation 15min, obtains
The solution of water white transparency;It is preferred that the Na2EDTA、GdCl3、YbCl3Molar ratio with L-arginine is 250.00:3.34:
30.06:70.00;The GdCl3It may be replaced by DyCl3Or HoCl3;
Step 2, the solution for the water white transparency for obtaining step 1 are transferred in reaction kettle, are reacted 10h at 200 DEG C, are treated it
After being cooled to room temperature, by the way that supernatant, rotating speed 11000rpm, time 20min is collected by centrifugation;
Step 3, the supernatant for obtaining step 2 are transferred in dialysis membrane, and are dialysed with ultra-pure water;
Step 4, will obtain Gd/Yb@after micro-filtrate membrane filtration that the solution aperture after dialysis is 0.22 μm, freeze-drying
CDs。
Embodiment
Weigh with scale Na2EDTA (93.06mg, 0.25mmol), GdCl3(0.88mg, 3.34 μm of ol), YbCl3
(8.48mg, 30.06 μm of ol) and L-arginine (12.54mg, 0.07mmol) are dissolved in 20mL deionized waters, and beaker is placed on magnetic
15min is stirred on power blender, obtains the solution of water white transparency.The solution is transferred to 50 milliliters of ptfe autoclaves
In, and put it into baking oven and react 10h at 200 DEG C.After it is cooled to room temperature, by the way that supernatant is collected by centrifugation, rotating speed is
11000rpm, 20min is to remove black precipitate for centrifugation, repeatedly for three times.Obtained brown color supernatant is transferred to dialysis membrane
In (MWCO 1000), and with ultra-pure water dialyse 24h.A water is changed per 4h, removes unnecessary unreacted material.Finally obtain
Solution with 0.22 μm of micro-filtrate membrane filtration, the solution of filtering is freeze-dried using vacuum freeze dryer, obtains Gd/Yb@CDs
Nano-particle.Elemental analysis result proves the percentage of carbon in obtained Gd/Yb@CDs nano-particles, nitrogen, oxygen, gadolinium and ytterbium element
Content is respectively 30.35%, 8.67%, 32.20%, 7.40% and 21.38%.
By GdCl in above-described embodiment3Replace with DyCl3Or HoCl3, it is corresponding be prepared Gd/Dy@CDs nano-particles or
Gd/Ho@CDs nano-particles.
Fig. 1 is the HRTEM photos for the Gd/Yb@CDs nano-particles that embodiment is prepared, as seen from the figure:Gd/Yb@CDs
Nano-particle is spherical in single dispersing, and average grain diameter is about 5.26 ± 0.93nm (Figure 1A);By Figure 1B it can be seen that clearly
Lattice fringe, spacing of lattice 0.213nm, corresponding to (100) crystal face of graphitic carbon, this is consistent with document report before.
Fig. 2 and 3 is respectively XPS the and FTIR spectrograms that the present invention implements the Gd/Yb@CDs nano-particles of preparation, can by Fig. 2
Know Gd/Yb@CDs nano-particles by C 1s (284.5eV), N 1s (399.2eV) and O 1s (531.1eV), Gd 3d (1186eV)
Formed with Yb 4d (184.6eV) element, it was demonstrated that rare earth Gd and Yb are successfully mixed in carbon dots.Gd/Yb@CDs as shown in Figure 3
Similar absorption band is shown with the FT-IR spectrum of CDs:In 3500~3200cm-1The absworption peak at place is stretched corresponding to O-H and N-H
Contracting vibration, in 1100cm-1Locate as C-N stretching vibrations, and the peak of COO- groups is from 1632cm-1It is changed into 1615cm-1, may be due to
Gd3+/Yb3+Caused by interaction between the arginic carboxyls of EDTA/L-.These characteristic peaks further demonstrate hydroxyl,
The presence of carboxylic acid and amino, it is consistent with XPS results.Gd3+And Yb3+After chelating, overall FT-IR spectrum peak shape does not have significant change,
Illustrate that the doping of rare-earth Gd/Yb has not significant impact carbon dots surface functional group.
In view of free Gd3+It can suppress internal Ca2+Passage so that induce serious cytotoxicity (as cardiovascular and
Neurotoxicity), thus, the bag filter (MWCO=1000) containing Gd/Yb@CDs is placed in serum solution by we, is carried out
Dialyse 24h, and 0.4mL is taken out when one section, with the Gd of ICP-OES measurement Gd/Yb@CDs3+Leakage, as shown in figure 4, & generations in figure
Gd in the initial nano-particle of table3+Content.As shown in Figure 4, almost without the Gd detected in serum solution3+Leakage, this can
Can be due to Gd3+There is strong interaction between carbon dots.
Toxicity of the Gd/Yb@CDs to HeLa and 4T1 cells is studied using mtt assay.Fig. 5 for HeLa cells and 4T1 cells with
The Gd/Yb@CDs of various concentrations are incubated the cell survival rate after 4h and 24h jointly, and each Gd/Yb@CDs concentration is corresponding in Fig. 5
Cell survival rate is labeled as a, b, c, d from left to right, is only marked out in figure when Gd/Yb CDs concentration is 0.As shown in Figure 5:
After 4h is cultivated, the survival rate and propagation of two kinds of cell line are barely affected.24h is extended to, even if the concentration of Gd/Yb@CDs
Up to 1mg/mL, cell survival rate is still above 85%.These it is preliminary test result indicates that, the Gd/Yb@CDs of preparation have
Relatively low toxicity.This hypotoxicity also comes from the chemical stability of Gd/Yb@CDs higher.Compared to partly leading with heavy metal toxicity
Body quantum dot, the hypotoxicity of Gd/Yb CDs make it have potential application prospect in biological and medical field.
Fig. 6 is the spectrogram of the UV-Vis of Gd/Yb@CDs, and wherein Fig. 6 A are absorption spectrum, Fig. 6 B are excitation/emission fluorescence
Spectrum.As shown in Figure 6:Identical absworption peak is presented in CDs and Gd/Yb@CDs at 273nm, this jumps corresponding to n → π * of C=O
Move.Under 365nm ultra violet lamps, bright blue-fluorescence (Fig. 6 A illustrations) is presented in the faint yellow aqueous solutions of Gd/Yb@CDs.Gd/
Yb@CDs also show the excitation-emission behavior relied on, this is generally existing as caused by the surface state emission trap of different-energy
As.With the change of excitation wavelength, corresponding surface state emission trap is occupied an leading position, so that it is existing to cause excitation wavelength to rely on
As.From Fig. 6 B:When excitation wavelength is changed into 370nm from 320nm, emission peak is moved to 463nm from 407nm.When sample swashs
When sending out 340nm, maximum fluorescence emission intensity is 418nm.It is 16.84% by the use of quinine sulfate as the quantum yield of reference solution,
Slightly above the 13.4% of Gd@CDs.In addition, have studied the fluorescent stability of Gd/Yb@CDs under 365nm ultraviolet lamps, exposed up to 2h
Under ultraviolet lamp, luminous intensity does not still change light, shows that Gd/Yb@CDs have excellent optical stability.
In order to investigate performances of the Gd/Yb@CDs in terms of fluorescence imaging, we are by HeLa cells and 1mg mL-1Gd/Yb@
CDs is incubated 2h jointly.Use fluorescence microscope capture images under light field and details in a play not acted out on stage, but told through dialogues respectively.Fig. 7 is HeLa cells and Gd/Yb@
CDs (1mg/mL) is incubated the cell image after 2h jointly, wherein (A) is bright-field image;(B) it is fluoroscopic image.Exist as shown in Figure 7
Under light field, treated cell still maintains complete form;In details in a play not acted out on stage, but told through dialogues, HeLa cells show very strong blueness
Fluorescence.In addition, it will be seen that Gd/Yb@CDs are predominantly located in cytoplasm, this is identical with the CDs behaviors reported in the past.This
Show in a short period of time, Gd/Yb@CDs can enter intracellular space by cell membrane barrier.
In order to investigate Gd/Yb@CDs nano-particles in T1Performance in terms of-MR imagings, first, using deionized water as pair
According to the water pipe imaging of measure various concentrations nano-particle aqueous solution.Magnevist (Gd-DTPA), FDA ratify and are widely used in
Clinical contrast agent, is chosen as control group.With Gd3+Concentration increases (0~0.36mM), two groups of T1The MR picture signals of-weighting
Gradual blast (Fig. 8, a represents Gd-DTPA in figure, and b represents Gd/Yb@CDs), but under same concentration this implementations preparation Gd/Yb@
CDs nano-particle contrasting effects are more preferable.For further qualitative assessment contrast effect, 9.4T standard inversion recovery pulse sequences are used
The Gd/Yb@CDs solution of row measurement various concentrations and the longitudinal relaxation time (T of Gd-DTPA1)。T1Reciprocal value and Gd3+It is dense
There are good linear relationship between degree, the slope of fit line is longitudinal relaxation efficiency (r1), it is usually used in evaluating MRI contrast agent
Performance.The r of Gd/Yb@CDs1It is worth for 6.65mM-1s-1(Fig. 9), higher than clinical Gd-DTPA (r1=3.69mM-1s-1), it is to have reported
Gd@CDs (the particle diameter 12nm, r in road1=5.88mM-1S-1) 1.13 times.The strong relaxation property of Gd/Yb@CDs is mainly due to grain
Footpath is smaller, can increase S/V values and then increase the binding capacity of metal ion and hydrone, in addition, the presence of hydrophilic radical also exists
R is promoted to a certain extent1Enhancing.
Rare earth element y b and Gd have intrinsic X-ray absorbability, and therefore, Gd/Yb@CDs nano-particles can also be used for
CT is imaged.Iobitridol, clinically common CT contrast agent, as a control group.Two groups are tested under the X-ray energy of 120kV
Water pipe CT images (Figure 10), with Yb3+With the increase of I concentration, CT brightness gradually strengthens.In contrast, under same concentrations,
Gd/Yb@CDs show the contrast effect than iobitridol higher.For further qualitative assessment CT contrasting effects, Gd/ is measured
The X-ray attenuation ability of Yb@CDs.As shown in figure 11, HU values and Yb3+Or there is good linear relationship, Gd/ between the concentration of I
The slope of Yb@CDs is about 45.42HU Lg-1, it will be apparent that higher than iobitridol (31.83HU L g-1).This is mainly due to Yb's
Attenuation coefficient (is 3.88cm during 100keV2/ g) more than the attenuation coefficient of I (it is 1.94cm during 100keV2/g).In short, result table
Bright, Gd/Yb@CDs have very big potentiality in MRI/CT imagings as local contrast enhancing probe.
Obviously, the above embodiments are merely examples for clarifying the description, and the restriction not to embodiment.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of change or
Change.There is no necessity and possibility to exhaust all the enbodiments.And the obvious change thus extended out or
Among changing still in the protection domain of the invention.
Claims (10)
- A kind of double 1. rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes, it is characterised in that be by carbon, nitrogen, oxygen, The gadolinium and ytterbium codope carbon dots, expression formula of gadolinium and ytterbium element composition are Gd/Yb@CDs.
- 2. double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes according to claim 1, its feature exist In the ytterbium element may be replaced by dysprosium or holmium element.
- 3. double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes according to claim 1, its feature exist In it is in monodisperse spherical, and average grain diameter is 5.26 ± 0.93nm.
- 4. double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes according to claim 1, its feature exist In the percentage composition of, the carbon, nitrogen, oxygen, gadolinium and ytterbium element be respectively 30.35%, 8.67%, 32.20%, 7.40% and 21.38%.
- 5. the preparation side of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes according to claim 1 Method, it is characterised in that comprise the following steps:Step 1, by Na2EDTA、GdCl3、YbCl3It is dissolved in L-arginine in deionized water, magnetic agitation, obtains water white transparency Solution;Step 2, the solution for the water white transparency for obtaining step 1 are transferred in reaction kettle, react 10h at 200 DEG C, treat its cooling To room temperature, by the way that supernatant is collected by centrifugation;Step 3, the supernatant for obtaining step 2 are transferred in dialysis membrane, and are dialysed with ultra-pure water;Step 4, will obtain Gd/Yb@CDs after the solution micro-filtrate membrane filtration after dialysis, freeze-drying.
- 6. the preparation side of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes according to claim 5 Method, it is characterised in that the GdCl3It may be replaced by DyCl3Or HoCl3。
- 7. the preparation side of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes according to claim 5 Method, it is characterised in that the Na2EDTA、GdCl3、YbCl3Molar ratio with L-arginine is 250.00:3.34:30.06: 70.00。
- 8. the preparation side of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes according to claim 5 Method, it is characterised in that the time of magnetic agitation is 15min in step 1.
- 9. the preparation side of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes according to claim 5 Method, it is characterised in that rotating speed when supernatant being collected by centrifugation in step 2 is 11000rpm, time 20min.
- 10. the preparation side of double rear-earth-doped carbon dots magnetic resonance/CT/ fluorescence multi-modality imaging probes according to claim 5 Method, it is characterised in that the aperture of microfiltration membranes described in step 4 is 0.22 μm.
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