CN114591729B - Near infrared IIb fluorescent probe, nanoparticle, and preparation method and application thereof - Google Patents
Near infrared IIb fluorescent probe, nanoparticle, and preparation method and application thereof Download PDFInfo
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- 239000002105 nanoparticle Substances 0.000 title claims abstract description 51
- 239000007850 fluorescent dye Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000003384 imaging method Methods 0.000 claims abstract description 17
- 229920000547 conjugated polymer Polymers 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims description 12
- -1 2-octyl dodecyl Chemical group 0.000 claims description 11
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 238000010521 absorption reaction Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 229920000642 polymer Polymers 0.000 claims description 7
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 7
- 239000012498 ultrapure water Substances 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000002872 contrast media Substances 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- LYRCQNDYYRPFMF-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C LYRCQNDYYRPFMF-UHFFFAOYSA-N 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 238000002604 ultrasonography Methods 0.000 claims description 3
- 239000003054 catalyst Chemical class 0.000 claims description 2
- 238000000975 co-precipitation Methods 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims description 2
- ZIIMIGRZSUYQGW-UHFFFAOYSA-N 4,7-bis(5-bromothiophen-2-yl)-2,1,3-benzothiadiazole Chemical class S1C(Br)=CC=C1C(C1=NSN=C11)=CC=C1C1=CC=C(Br)S1 ZIIMIGRZSUYQGW-UHFFFAOYSA-N 0.000 claims 1
- FYNROBRQIVCIQF-UHFFFAOYSA-N pyrrolo[3,2-b]pyrrole-5,6-dione Chemical compound C1=CN=C2C(=O)C(=O)N=C21 FYNROBRQIVCIQF-UHFFFAOYSA-N 0.000 abstract description 8
- 210000004204 blood vessel Anatomy 0.000 abstract description 6
- 230000005284 excitation Effects 0.000 abstract description 2
- 238000012544 monitoring process Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 238000000295 emission spectrum Methods 0.000 description 5
- 238000000799 fluorescence microscopy Methods 0.000 description 5
- 238000009210 therapy by ultrasound Methods 0.000 description 5
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- OPYRETPBRCRXQU-UHFFFAOYSA-N 4,6-dihydro-1h-pyrrolo[3,2-b]pyrrol-5-one Chemical compound N1C=CC2=C1CC(=O)N2 OPYRETPBRCRXQU-UHFFFAOYSA-N 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000012632 fluorescent imaging Methods 0.000 description 2
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 2
- 150000004867 thiadiazoles Chemical class 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 150000002910 rare earth metals Chemical class 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
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Abstract
The invention discloses a near infrared IIb fluorescent probe based on DPP (pyrrolo-pyrrole-dione) conjugated polymer DT-R, and discloses a preparation method of the fluorescent probe and nano particles thereof. The maximum emission peak of the prepared nano-particles is in the near infrared two-region (NIR-II) range, and the longest emission wavelength can extend to the near infrared IIb region (NIR-IIb). The nano particles provided by the invention can realize the mouse blood vessel imaging of NIR-IIb under 808nm laser excitation, have high imaging resolution and signal-to-noise ratio, and have wide application prospects in the aspects of blood vessel monitoring, repairing and the like.
Description
Technical Field
The invention belongs to the field of biological optical diagnosis and treatment, and particularly relates to a near infrared IIb fluorescent probe, a nanoparticle, a preparation method and application thereof.
Background
Fluorescence imaging (FLI) has its unique advantages over various conventional imaging modalities, such as Positron Emission Tomography (PET), X-ray Computed Tomography (CT), and Nuclear Magnetic Resonance Imaging (NMRI), including high spatial-temporal resolution and rapid detection in real time, and is one of the mainstream imaging modalities in recent years. To date, FLI has matured or primarily been applied to high resolution vascular imaging, gastrointestinal imaging, and imaging guided clinical oncology resections. In recent years, the emission wavelength at 900-1700nm, namely, the second near infrared (NIR-II), has attracted extensive and intensive research by researchers at home and abroad. NIR-II imaging exhibits deeper penetration (10 mm) compared to the conventional imaging range, including the visible region (400-700 nm) and the first near infrared window (NIR-I, 700-900 nm), excellent high temporal and spatial resolution, and high signal to noise ratio (SBR) due to reduced autofluorescence and photon scattering. The NIR-II region can be further subdivided into three sub-regions NIR-IIa' (1000-1300 nm), NIR-IIa (1300-1400 nm) and NIR-IIb (1500-1700 nm), and its imaging resolution and penetration depth can be further improved with increasing wavelength. At present, many inorganic nanomaterials such as quantum dots and rare earth nanoparticles are designed and constructed for NIR-IIb fluorescence imaging. Despite their high fluorescence intensity, their potential long-term biotoxicity problems greatly limit their clinical practical use. Therefore, the development of novel efficient organic NIR-IIb fluorescent contrast agents has become a hotspot and difficulty in current research.
Disclosure of Invention
The invention aims to overcome the defects, and provides a near infrared IIb fluorescent probe and nanoparticles thereof, wherein the near infrared IIb fluorescent probe has high brightness, can be used for NIR-IIb fluorescent imaging, and is easy to synthesize, low in toxicity, green and safe.
In order to achieve the above purpose, the invention is realized by the following technical scheme:
the invention provides a near infrared IIb fluorescent probe, which is based on DPP (pyrrolo-pyrrole-dione) conjugated polymer DT-R, wherein the structural formula of the DT-R is as follows:
preferably, the R group in formula 1 may be selected from H, F, cl, br, I or NO 2 The optional structure is as follows:
the invention also provides a preparation method of the near infrared IIb fluorescent probe, namely, the synthesis of the conjugated polymer DT-R comprises the following steps:
2, 5-bis (2-octyldodecyl) -3, 6-bis (5- (trimethyltin) thiophen-2-yl) -2, 5-dihydropyrrolo [3,4-c]Pyrrole-1, 4-dione, R-substituted 4, 7-bis (5-bromothiophen-2-yl) benzo [ c ]][1,2,5]Thiadiazole derivative and catalyst Pd (PPh) 3 ) 4 Dissolving in toluene as an organic solvent in a molar ratio of 1:1:1, carrying out reflux reaction under the protection of nitrogen, cooling, and settling to obtain the target polymer. The differently substituted 4, 7-bis (5-bromothiophen-2-yl) benzo [ c ]][1,2,5]The thiadiazole derivative may be H, F, cl, br, I or NO 2 And (3) substitution. The synthesis isThe method has the advantages of simple reaction steps, simple conditions and easy synthesis.
The invention also provides a nanoparticle of the near infrared IIb fluorescent probe, which is prepared by using an amphiphilic polymer F127 and a nano coprecipitation method based on the DPP conjugated polymer DT-R shown in the formula 1.
The nanoparticle of the near infrared IIb fluorescent probe has the maximum absorption wavelength in an NIR-I region and the maximum emission wavelength in an NIR-II region in an aqueous solution.
The nanoparticle of the near infrared IIb fluorescent probe can extend to 1500-1700nm in the tail peak of the emission wavelength in an aqueous solution.
The invention also provides a preparation method of the nanoparticle of the near infrared IIb fluorescent probe, which comprises the following steps:
dissolving DPP conjugated polymers DT-R and F127 shown in formula 1 in an organic solvent, adding the organic solvent into ultrapure water under ultrasonic treatment, and removing the organic solvent after ultrasonic treatment to obtain the nano particles.
Preferably, the mass ratio of DT-R to F127 is 1:20, the volume ratio of the organic solvent to ultrapure water is 1:10, the organic solvent can be tetrahydrofuran, the ultrasonic time is 5min, and the nitrogen flow is adopted for removing the organic solvent, and the time is 30min.
The invention also provides application of the near infrared IIb fluorescent probe in preparing a contrast agent in living blood vessel imaging in an NIR-IIb region excited by 808nm laser, namely application of the nanoparticle serving as the contrast agent in living blood vessel imaging in the NIR-IIb region excited by 808nm laser, has high imaging resolution and signal to noise ratio, and has wide application prospects in aspects of blood vessel monitoring, repairing and the like.
Compared with the prior art, the invention has the beneficial effects that:
the near infrared IIb fluorescent probe based on the pyrrolopyrrole Dione (DPP) conjugated polymer has high fluorescent brightness, is easy to synthesize, good in structural modification, low in toxicity and green and safe in synthesis process.
The nano particle of the near infrared IIb fluorescent probe is absorbed in an NIR-I region, the whole emission wavelength is in an NIR-II region, and the tail peak can extend to the NIR-IIb region, so that the nano particle can be used for preparing an 808nm laser excited NIR-IIb high-resolution angiography contrast agent, and the preparation process is simple and good in repeatability.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a NIR-IIb fluorescent probe provided in example 1;
FIG. 2 is a DLS and TEM image of DT-H nanoparticles as described in example 1;
FIG. 3 is an absorption and emission spectrum of DT-H nanoparticles according to example 1 in aqueous solution;
FIG. 4 is a graph showing the emission spectrum of DT-H nanoparticles of example 1 at 1400-1800nm in aqueous solution;
FIG. 5 is a chart showing the hydrogen nuclear magnetic resonance spectrum of an NIR-IIb fluorescent probe provided in example 2;
FIG. 6 is a diagram of DT-NO as described in example 2 2 DLS and TEM images of the nanoparticles of (a);
FIG. 7 is a diagram of DT-NO as described in example 2 2 Absorption and emission patterns of the nanoparticles in aqueous solutions;
FIG. 8 is DT-NO as described in example 2 2 An emission spectrum diagram of 1400-1800nm of the nano particles in an aqueous solution;
FIG. 9 is a diagram of DT-NO as described in example 2 2 NIR-IIb in vivo imaging of nanoparticles in vivo.
Detailed Description
Preferred embodiments of the present invention will be described in more detail below with reference to the accompanying drawings and specific examples.
Example 1
An NIR-IIb fluorescent probe based on a pyrrolopyrrolidone (DPP) conjugated polymer, wherein conjugated polymer DT-H has the following structure:
the synthetic steps of the conjugated polymer DT-H comprise: 2, 5-bis (2-octyldodecyl) -3, 6-bis (5- (trimethyltin) thiophene-2-yl) -2, 5-dihydropyrrolo [3,4-c]Pyrrole-1, 4-dione (0.05 g,0.042 mmol), 4, 7-bis (5-bromothiophen-2-yl) benzo [ c ]][1,2,5]Thiadiazole (0.0193 g,0.042 mmol), pd (PPh) 3 ) 4 (5 mg,0.0042 mmol) and 10mL toluene in N 2 Adding the mixture into a 50mL preset reaction tube under the atmosphere, refluxing the mixture for 7H, cooling to room temperature, dropwise adding the reaction solution into 200mL methanol solution, and filtering under reduced pressure to collect the mixture to obtain a final product DT-H (yield 58%), wherein a nuclear magnetic resonance hydrogen spectrum is shown in figure 1, peaks between 6.5 and 8.0 in the figure are hydrogen on aromatic ring thiophene or benzene ring, and peaks between 0 and 2.0 are hydrogen on alkyl chain. The synthetic route is as follows:
the embodiment provides a nanoparticle of the near infrared IIb fluorescent probe DT-H, and the preparation method comprises the following steps:
step one: weighing 0.5mg of polymer DT-H, dissolving 10mg of F127 in 1mL of tetrahydrofuran, and performing ultrasonic dissolution;
step two: rapidly adding the mixture solution into 5mL of ultrapure water under ultrasonic, and continuing ultrasonic treatment for 5min;
step three: tetrahydrofuran was removed from the resulting solution to give 100. Mu.g/mL of DT-H nanoparticle solution.
The DLS and TEM of the DT-H nanoparticle of this example are shown in FIG. 2, the diameter of the nanoparticle is 134nm, and the nanoparticle is in a typical spherical shape; the absorption and emission patterns of the DT-H nano particles in the aqueous solution are shown in figure 3, and the maximum absorption of the nano particles is 732nm, the maximum emission wavelength is 1080nm, and the nano particles belong to the near infrared two-region range; the emission spectrum of the DT-H nanoparticles in aqueous solution is shown in a graph of 1400-1800nm, and an emission peak can be obviously observed in the graph, wherein the emission belongs to the emission of NIR-IIb, which shows that the DT-H nanoparticles can be used for living body imaging of the NIR-IIb.
Example 2
NIR-IIb fluorescent probe based on pyrrolopyrrole Dione (DPP) conjugated polymerNeedles in which the conjugated polymer DT-NO 2 The structure is as follows:
the conjugated polymer DT-NO 2 The synthesis steps of (a) comprise: 2, 5-bis (2-octyldodecyl) -3, 6-bis (5- (trimethyltin) thiophen-2-yl) -2, 5-dihydropyrrolo [3,4-c]Pyrrole-1, 4-dione (0.1 g,0.084 mmol), 4, 7-bis (5-bromothiophen-2-yl) -5, 6-dinitrobenzo [ c ]][1,2,5]Thiadiazole (0.04 g,0.084 mmol), pd (PPh) 3 ) 4 (10 mg,0.0084 mmol) and 10mL toluene in N 2 Adding the mixture into a 50mL preset reaction tube under the atmosphere, refluxing the mixture for 7h, cooling to room temperature, dripping the reaction solution into 200mL methanol solution, and filtering and collecting the mixture under reduced pressure to obtain a final product DT-NO 2 The yield is 60%, and the nuclear magnetic resonance hydrogen spectrum is shown in figure 5, wherein the peaks between 6.5 and 8.0 are the hydrogen on the aromatic thiophene or benzene ring, and the peaks between 0 and 2.0 are the hydrogen on the alkyl chain. The synthetic route is as follows:
the embodiment provides the near infrared IIb fluorescent probe DT-NO 2 The preparation method of the nanoparticle comprises the following steps:
step one: weighing polymer DT-NO 2 0.5mg,10mg of F127 are dissolved in 1mL of tetrahydrofuran, and dissolved by ultrasound;
step two: rapidly adding the mixture solution into 5mL of ultrapure water under ultrasonic, and continuing ultrasonic treatment for 5min;
step three: tetrahydrofuran was removed from the resulting solution to give 100. Mu.g/mL DT-NO 2 Nanoparticle solutions.
DT-NO according to this example 2 As shown in fig. 6, DLS and TEM of the nanoparticles of 118nm in diameter, which are uniformly dispersed spheres; the DT-NO 2 Absorption and development of nanoparticles in aqueous solutionsThe emission spectrum is shown in fig. 7, and it can be found from the graph that the maximum absorption and emission peaks of the nanoparticles are respectively at 782nm and 1090nm; the DT-NO 2 The spectrum of 1400-1800nm emission in aqueous solution is shown in FIG. 8, in which the NIR-IIb emission peak is clearly visible, indicating DT-NO 2 The nano particles can be used as NIR-IIb fluorescent imaging contrast agents; the DT-NO 2 As shown in figure 9, the wavelength of excitation light source is 808nm, and the adopted filters are respectively 480 nm LP,1300-1400nm and 1500nm LP, the imaging graph shows that the NIR-IIb region (1500 nm LP) has the best imaging effect, and the whole blood vessel of the mouse is clearly visible, thus indicating that the nanoparticle has excellent NIR-IIb fluorescence imaging performance.
Example 3
An NIR-IIb fluorescent probe based on a pyrrolopyrrolidone (DPP) conjugated polymer, wherein conjugated polymer DT-F has the following structure:
the synthetic steps of the conjugated polymer DT-F comprise: 2, 5-bis (2-octyldodecyl) -3, 6-bis (5- (trimethyltin) thiophen-2-yl) -2, 5-dihydropyrrolo [3,4-c]Pyrrole-1, 4-dione (0.1 g,0.084 mmol), 4, 7-bis (5-bromothienyl-2-) -5, 6-difluoro-2, 1, 3-benzothiadiazole (0.04 g,0.084 mmol), pd (PPh) 3 ) 4 (10 mg,0.0084 mmol) and 10mL toluene in N 2 Added to 50mL of a preset reaction tube under atmosphere, the mixture was refluxed for 7 hours, cooled to room temperature, and then the reaction solution was added dropwise to 200mL of methanol solution, and the mixture was collected by filtration under reduced pressure to give the final product DT-F (yield: 52%) which was synthesized as follows:
the embodiment provides a nanoparticle of the near infrared IIb fluorescent probe DT-F, and the preparation method comprises the following steps:
step one: weighing 0.5mg of polymer DT-F, dissolving 10mg of F127 in 1mL of tetrahydrofuran, and performing ultrasonic dissolution;
step two: rapidly adding the mixture solution into 5mL of ultrapure water under ultrasonic, and continuing ultrasonic treatment for 5min;
step three: tetrahydrofuran was removed from the resulting solution to give 100. Mu.g/mL of DT-F nanoparticle solution.
The foregoing description of embodiments of the invention has been presented for purposes of illustration and description, and is not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the various embodiments described, and these modifications and variations should also be considered as being within the scope of the invention.
Claims (8)
1. A near infrared IIb fluorescent probe, characterized in that the fluorescent probe is based on DPP conjugated polymer DT-R, the structural formula of which is as follows:
the R group in the formula 1 is NO 2 。
2. A method for preparing the near infrared IIb fluorescent probe according to claim 1, wherein the synthesis of the conjugated polymer DT-R comprises the following steps:
dissolving 2, 5-bis (2-octyl dodecyl) -3, 6-bis (5- (trimethyltin) thiophene-2-yl) -2, 5-dihydropyrrolo [3,4-c ] pyrrole-1, 4-dione and R-substituted 4, 7-bis (5-bromothiophene-2-yl) benzo [ c ] [1,2,5] thiadiazole derivative and catalyst in an organic solvent in a molar ratio of 1:1:1, carrying out reflux reaction under the protection of nitrogen, cooling and settling to obtain the target polymer.
3. The nanoparticle of the near infrared IIb fluorescent probe according to claim 1, wherein the nanoparticle is prepared by using an amphiphilic polymer F127 and a nano coprecipitation method based on DT-R according to claim 1.
4. The nanoparticle of the near infrared IIb fluorescent probe of claim 3, wherein the nanoparticle is in aqueous solution with a maximum absorption wavelength in the NIR-I region and a maximum emission wavelength in the NIR-II region.
5. The nanoparticle of the near infrared IIb fluorescent probe according to claim 3, wherein the nanoparticle is capable of extending an emission wavelength tail to 1500 to 1700nm in an aqueous solution.
6. A method for preparing the nanoparticle of near infrared IIb fluorescent probe according to claim 3, comprising the steps of:
dissolving the DT-R and F127 of claim 1 in an organic solvent, adding the organic solvent to ultrapure water under ultrasound, and removing the organic solvent after ultrasound to obtain the nanoparticles.
7. The method for preparing nanoparticles of near infrared IIb fluorescent probe as claimed in claim 6, wherein the mass ratio of DT-R and F127 is 1:20, and the volume ratio of organic solvent to ultrapure water is 1:10.
8. Use of a near infrared IIb fluorescent probe as claimed in claim 1 for the preparation of a contrast agent for 808nm laser-excited NIR-IIb region living vascular imaging.
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