CN115678535A - Water-soluble quantum dot nano material and preparation method and application thereof - Google Patents
Water-soluble quantum dot nano material and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a water-soluble quantum dot nano material and a preparation method and application thereof, wherein the nano material comprises quantum dots and a terminal carboxyl polylactic acid-glycolic acid copolymer coated on the surfaces of the quantum dots. The invention utilizes the terminal carboxyl polylactic acid-glycolic acid copolymer to CsPbBr 3 Packaging perovskite quantum dots to prepare water-soluble calcium titaniumThe mineral nanocrystalline material can keep the water and oxygen resistance (more than or equal to 30 days) while keeping high quantum yield (PLQY = 88%), and almost completely keeps the optical performance of perovskite quantum dots.
Description
Technical Field
The invention belongs to the field of materials science and biomedicine, and relates to a water-soluble quantum dot nano material, a preparation method thereof and application thereof in brain glioma cell imaging, in particular to a water-soluble quantum dot nano material stably existing in a water system for a long time, a preparation method thereof and application thereof in brain glioma cell imaging.
Background
Brain glioma is one of common diseases in the nervous system, and has the characteristics of easy invasion, easy metastasis and diffusion, high recurrence rate and high lethality rate, and multi-modal imaging combining various modes such as MRI imaging, near infrared fluorescence imaging, ultrasound and the like in the operation is a common method for guiding tumor resection. MRI imaging can provide good resolution and accuracy, but does not provide real-time continuous guidance and is expensive; ultrasound is portable and low cost, but has limited intraoperative imaging contrast and resolution, making accurate real-time detection difficult. Therefore, fluorescence imaging is extremely advantageous in detecting tumors in surgical operations, not only can be imaged in real time, but also has high resolution and high accuracy, and can provide real-time and direct visual guidance for tumor cells.
With the increasing demand of tumor cell detection in rapid real-time surgery, the requirement of fluorescent biological detection probes is higher and higher. Although many studies have used traditional fluorescent substances to guide the excision of glioma, the detection requirements of high fluorescence efficiency, narrow emission, low interference and the like cannot be met due to poor fluorescence stability and low fluorescence efficiency, so that the development of a novel nano biological detection probe with high fluorescence intensity, narrow emission and good biocompatibility is of great significance.
The perovskite nanocrystal material becomes a fluorescent labeling material with the highest quantum yield in the existing material due to the size effect and quantum confinement of the material. The perovskite nanocrystal material also has the advantages of narrow emission peak (< 20 nm), controllable emission peak position, wide excitation wavelength range, easy synthesis and the like. However, perovskite quantum dots are not resistant to water and oxygen, so that the application and development of the perovskite quantum dots in various fields such as bioscience and medicine are severely limited. Therefore, how to modify the perovskite quantum dots to construct a nano biological probe which can fully exert the advantages of the material and has good biocompatibility is urgent to be solved.
Disclosure of Invention
In order to improve the technical problems, the invention provides a water-soluble quantum dot nano material, a preparation method thereof and application thereof in brain glioma cell imaging.
The technical scheme of the invention is as follows:
a water-soluble quantum dot nano material comprises quantum dots and a carboxyl-terminated polylactic acid-glycolic acid copolymer (OH-PLGA-COOH) coated on the surfaces of the quantum dots.
According to an embodiment of the present invention, the water-soluble quantum dot nanomaterial is a nanocrystal.
According to an embodiment of the invention, the average particle size of the quantum dots is 5 to 20nm, such as 10 to 15nm; illustratively, the average particle size of the quantum dots is 5nm, 8nm, 10nm, 12nm, 15nm, or 20nm.
According to an embodiment of the present invention, the average particle size of the water-soluble quantum dot nanomaterial is larger than the average particle size of the quantum dot, for example, greater than 5nm to 100nm, preferably 15 to 80nm, more preferably 50 to 70nm, and exemplarily, may be 8nm, 10nm, 15nm, 20nm, 30nm, 40nm, 50nm, 60nm, 70nm, 80nm, 90nm, or 100nm.
According to the embodiment of the invention, the mass ratio (mg: mg) of the quantum dot to the carboxyl-terminated polylactic acid-glycolic acid copolymer is 116 (50-200); for example, 116 (60-150) may be used. For example, the following.
According to embodiments of the present invention, the coating may be a full coating, or a partial coating. For example, when the mass ratio (mg: mg) of the quantum dot to the terminal carboxyl polylactic acid-glycolic acid copolymer is at least 116.
According to an embodiment of the present invention, the quantum dot may be a perovskite quantum dot, a carbon quantum dot, a cadmium quantum dot, a zinc sulfide quantum dot, a sulfur quantum dot, or the like.
Illustratively, the perovskite quantum dot is CsPbBr 3 Perovskite quantum dots.
Wherein, the CsPbBr 3 Perovskite quantum dots are yellow in visible light and green in ultraviolet light (e.g., 365nm excitation).
According to an embodiment of the invention, the carboxyl-terminated polylactic acid-glycolic acid copolymer (OH-PLGA-COOH) has a number average molecular weight of 10000 to 200000, for example 100000 to 200000, and in the range of for example 110000 to 200000.
According to an embodiment of the present invention, the carboxyl-terminated polylactic acid-glycolic acid copolymer is a random copolymer of racemic lactide (DLLA) and Glycolide (GA); for example, the mass ratio of racemic lactide (DLLA) to Glycolide (GA) is (50-90) to (10-50), illustratively 90.
According to an embodiment of the invention, the water-soluble quantum dot nanomaterial comprises CsPbBr 3 Perovskite quantum dot and coating CsPbBr 3 And the terminal carboxyl polylactic acid-glycolic acid copolymer (OH-PLGA-COOH) on the surface of the perovskite quantum dot is marked as P-PQDs.
According to an embodiment of the present invention, the water-soluble quantum dot nanomaterial has almost the same optical properties as quantum dots; for example, P-PQDs have the same chemical formula as CsPbBr 3 Perovskite quantum dots have almost the same optical properties.
The invention also provides a preparation method of the water-soluble quantum dot nano material, which comprises the following steps: and heating and reacting the carboxyl-terminated polylactic acid-glycolic acid copolymer with the quantum dot to obtain the water-soluble quantum dot nano material.
According to the embodiment of the invention, the preparation method of the water-soluble quantum dot nano material specifically comprises the following steps:
(A1) Mixing and dissolving a raw material for preparing the quantum dots and a terminal carboxyl polylactic acid-glycolic acid copolymer in a solvent, and adding an organic ligand to form a stable solution;
(A2) And (2) adding the stable solution obtained in the step (A1) into an anti-solvent, heating for reaction, and precipitating the water-soluble quantum dot nano material by using an anti-solvent supersaturation method to prepare the water-soluble quantum dot nano material.
According to the inventionAccording to the technical scheme, the quantum dots are CsPbBr 3 In the case of perovskite quantum dots, the raw materials for preparing the quantum dots are CsBr and PbBr 2 。
Wherein, the CsPbBr 3 The perovskite quantum dots can be prepared by methods known in the art.
According to an embodiment of the present invention, in the step (A1), the mixing order of the raw material for preparing the quantum dot and the terminal carboxy polylactic acid-glycolic acid copolymer is not limited, for example, the raw material for preparing the quantum dot and the terminal carboxy polylactic acid-glycolic acid copolymer may be added to the solvent at the same time, or the raw material for preparing the quantum dot may be added to the solvent first, and then the terminal carboxy polylactic acid-glycolic acid copolymer may be added to the solvent.
According to an embodiment of the present invention, in the step (A1), the ratio (mg: mg) of the sum of the masses of the raw materials for preparing the quantum dots to the mass of the carboxyl-terminated polylactic acid-glycolic acid copolymer (OH-PLGA-COOH) is 116 (50-200), preferably 116 (60-150).
According to an embodiment of the present invention, in step (A1), the mass-to-volume ratio of the terminal carboxy polylactic acid-glycolic acid copolymer to the solvent is (5 to 30) mg:1mL, for example, 5 mg.
According to an embodiment of the present invention, in the step (A1), the solvent may be selected from one or two of N, N-Dimethylformamide (DMF), dimethyl sulfoxide (DMSO).
According to an embodiment of the present invention, in the step (A1), the organic ligand may be at least one selected from oleic acid, oleylamine, octylamine, for example, a mixture of oleic acid and oleylamine in any ratio.
Preferably, the volume ratio of the organic ligand to the solvent is (0.5 to 5): 10, such as (1 to 3): 10, exemplary 0.5.
According to an embodiment of the invention, step (A1) is carried out under anhydrous and anaerobic conditions. Preferably in an inert atmosphere, such as nitrogen or argon.
According to an embodiment of the present invention, in the step (A2), the antisolvent is at least one selected from the group consisting of toluene, chlorobenzene, and n-hexane.
According to an embodiment of the present invention, step (A2) comprises: firstly, dropwise adding the stable solution in the step (A1) into an anti-solvent to obtain a water-soluble quantum dot nano material solution; and (3) heating for reaction, collecting precipitates in a high-speed centrifugation mode after the reaction is finished, and performing ultrasonic dispersion in water to obtain the water-soluble quantum dot nano material.
Preferably, the volume ratio of the stabilizing solution to the anti-solvent is (0.1-5): 10, for example (0.5-3): 10.
Preferably, the dropping is slowly dropping dropwise, for example, at a rate of 6 to 12. Mu.L/s, illustratively 6. Mu.L/s, 8. Mu.L/s, 10. Mu.L/s, 12L/s.
Preferably, the dropwise addition is carried out under vigorous stirring of the anti-solvent.
Preferably, the water-soluble quantum dot nano-material solution is added into an excessive anti-solvent, heated, stirred and reacted, and the water-soluble quantum dot nano-material is precipitated.
For example, the stirring time is 5 to 10 hours, such as 5 hours, 7 hours, 8 hours, 10 hours. For example, the reaction temperature is 30 to 60 ℃, e.g., 40 to 50 ℃, such as 30, 40 ℃, 42 ℃, 45 ℃, 48 ℃, 50 ℃,60 ℃.
According to an embodiment of the present invention, the method for preparing the water-soluble quantum dot nanomaterial further comprises:
(A3) And (3) separating the water-soluble quantum dot nano material in the step (A2), taking the precipitate and drying to obtain the solid water-soluble quantum dot nano material.
According to an embodiment of the present invention, the method for preparing the water-soluble quantum dot nanomaterial further comprises:
(A4) And (D) dispersing the solid water-soluble quantum dot nano material obtained in the step (A3) in water to obtain a water-soluble quantum dot nano material solution.
The invention also provides the water-soluble quantum dot nano material prepared by the method.
According to the invention, the water-soluble quantum dot nano material is a solid water-soluble quantum dot nano material or a water-soluble quantum dot nano material solution.
Particularly, the water-soluble quantum dot nano material aqueous solution is a water-soluble quantum dot nano crystal aqueous solution.
The invention also provides application of the water-soluble quantum dot nano material in preparation of a nano probe or a kit for medical diagnosis.
For example, the nanoprobes may be fluorescent biological detection probes or cell imaging probes.
The invention also provides a nano probe which comprises the water-soluble quantum dot nano material.
According to an embodiment of the present invention, the nanoprobe is a biomaterial labeled with the water-soluble quantum dot nanomaterial.
According to an embodiment of the present invention, the biomaterial may be selected from one, two or more of antibodies, aptamers, polypeptides and the like. Illustratively, the biological material is a polypeptide; such as chlorotoxin polypeptides.
According to the embodiment of the invention, the nanoprobe can generate strong fluorescence in the range of 500-540 nm under the excitation of 365 +/-5 nm, and generate the strongest fluorescence at 515 +/-5 nm, namely green light.
According to an exemplary embodiment of the invention, the nanoprobe is a chlorotoxin polypeptide labeled by a water-soluble perovskite nano material P-PQDs, and is formed by electrostatic interaction of the P-PQDs and the chlorotoxin polypeptide.
According to an embodiment of the invention, the mass ratio of the water-soluble quantum dot nano material to the biological material is (10-50): 1, illustratively 10.
According to an embodiment of the invention, the average particle size of the nanoprobe is in the range of 20 to 100nm, illustratively 20nm, 30nm, 40nm, 45nm, 50nm, 55nm, 60nm, 70nm, 80nm, 90nm or 100nm.
The invention also provides a preparation method of the nano probe, which comprises the following steps: and coupling the water-soluble quantum dot nano material with the biological material to prepare the nano probe.
According to an embodiment of the invention, the preparation method comprises the steps of: mixing a water-soluble quantum dot nano material with a biological material, and obtaining the nano probe through strong charge difference electrostatic interaction;
the water-soluble nanomaterial and biomaterial have the meaning as described above.
According to an embodiment of the invention, the coupling is carried out in the presence of a solvent. Specifically, the solvent may be an ultrapure aqueous solution (e.g., pH = 6.42).
According to the embodiment of the invention, the mass ratio of the biological material to the water-soluble quantum dot nano material is 1 (10-50), such as 1.
According to an embodiment of the present invention, in the method for preparing the nanoprobe, the obtained nanoprobe may be stored in a refrigerated state. For example, the temperature for cold storage is 1 to 5 ℃, for example, 1 ℃,2 ℃,3 ℃, 4 ℃ or 5 ℃.
The invention also provides the nano probe prepared by the method.
The invention also provides a kit, and the kit comprises the nanoprobe.
The invention also provides application of the water-soluble quantum dot nano material, the nano probe or the kit in the fields of medical detection, medical diagnosis and treatment and the like.
Preferably, the medical test may be a cellular imaging or biological test. Preferably, for example, brain glioma cells are imaged.
According to an embodiment of the present invention, the nanoprobe or kit may recognize at least one of the following target analytes: antibodies, aptamers, polypeptides, antigens, target molecules, proteases, and the like. Such as polypeptides, e.g., chlorotoxin polypeptides, and the like.
The invention also provides a method for identifying the target analyte by using the nano probe or the kit, which comprises the following steps: and contacting the nano probe with the target analyte, and identifying through fluorescence detection.
According to the invention, the excitation wavelength of fluorescence detection is 365 nm-450 nm.
The invention has the beneficial effects that:
1. the invention utilizes terminal carboxyl polylactic acid-glycolic acid copolymer (OH-PLGA-COOH) to CsPbBr 3 The perovskite quantum dots are packaged to prepare the water-soluble perovskite nanocrystalline material, the water and oxygen resistance (more than or equal to 30 days) can be kept while the high quantum yield (PLQY = 88%) is kept, and the optical performance of the perovskite quantum dots is almost completely kept.
2. The product of the invention uses degradable polylactic acid-glycolic acid copolymer to coat the quantum dot material to prepare the biological nano probe, which not only keeps the high fluorescence intensity and narrow emission performance of the quantum dot, but also endows the quantum dot with the characteristics of good biocompatibility, no toxicity, environmental protection and the like.
3. The water-soluble quantum dot nanocrystalline biological nanoprobe can be used for simultaneously detecting multiple analytes in the medical field, can avoid false negative results caused by the crossing of emission peaks of fluorescent substances, improves the detection reliability, has universality, can realize the simultaneous detection of multiple targets, greatly meets the requirements of modern biotechnology and medical detection, and has important significance in the medical diagnosis and treatment field.
4. The water-soluble quantum dot nano material realizes electrostatic interaction through simple strong potential difference, can be simply and quickly coupled with biological materials, and avoids complicated coupling reaction. Meanwhile, the prepared kit has the advantages of low cost, simple operation and easy realization of commercialization.
5. The novel biological nano probe (taking a chlorotoxin nano probe as an example) is constructed based on the water-soluble quantum dot material, and glioma cells can be specifically identified, so that tumor tissues, tissues beside cancer and normal tissues can be distinguished, and real-time and direct visual guidance of tumor excision can be realized.
Drawings
FIG. 1 is a transmission electron microscope photograph of PQDs quantum dots of preparation example 1.
FIG. 2 is a transmission electron micrograph of P-PQDs perovskite nanocrystals of example 1.
FIG. 3 is a graph showing the fluorescence images of P-PQDs perovskite nanocrystals of example 1 under 420-450 nm excitation.
FIG. 4 is a graph showing the quantum yield of PQDs of preparation example 1 and P-PQDs perovskite nanocrystals of example 1.
FIG. 5 is a PL spectrum of P-PQDs perovskite nanocrystals of example 1.
FIG. 6 shows fluorescence emission spectra of the P-PQDs nanocrystals of example 1 and the nanoprobe Probe-PQDs of example 2.
FIG. 7 is a Zeta potential diagram of the P-PQDs quantum dot nanomaterial and chlorotoxin polypeptide (CTX) in example 1 and Probe-PQDs in example 2.
FIG. 8 is a photograph of fluorescence images of Probe-PQDs nanoprobes recognizing brain glioma 251 cells and HA cells in example 3.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to specific embodiments. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.
The carboxyl-terminated polylactic acid-glycolic acid copolymer (OH-PLGA-COOH) used in the following examples was purchased from dengailian bioengineering, ltd, with a number average molecular weight of 110000,dlla of 50 mass percent.
Preparation example 1
The preparation steps of the PQDs perovskite quantum dot are as follows:
(1) 42.5mg CsBr and 73.4mg PbBr 2 Dissolving in 5mL of N, N-Dimethylformamide (DMF) solvent, and adding 0.5mL of oleic acid and 0.25mL of oleylamine for stabilizing the solution after complete dissolution;
(2) Taking 500 mu L of the solution, placing the solution in a glove box, and adding N 2 Slowly dropwise adding (dropwise adding speed is 10 mu L/s) into 10mL of vigorously stirred toluene solution under the protection of atmosphere to obtainTo PQDs perovskite quantum dot solutions.
(3) And centrifuging the prepared PQDs perovskite quantum dot at 10000r/min for 20min, and separating to obtain a supernatant, thus obtaining a purified PQDs perovskite quantum dot solution which is transparent green.
FIG. 1 is a transmission electron microscope image of the prepared PQDs perovskite quantum dot, and the particle size of the PQDs perovskite quantum dot is about 12nm and can be seen from the image, and CsPbBr 3 The quantum dots are matched in size.
Example 1P-PQDs Water-soluble perovskite nanocrystals
In order to achieve the hydrophobic effect, on the basis of preparation example 1, a hydrophobic carboxyl-terminated polylactic acid-glycolic acid copolymer (OH-PLGA-COOH) is coated on the surface of a high-fluorescence perovskite quantum dot to form water-soluble perovskite nanocrystals P-PQDs, and the steps are as follows:
(1) 42.5mg CsBr and 73.4mg PbBr 2 Dissolving 90mg of terminal carboxyl polylactic acid-glycolic acid copolymer (OH-PLGA-COOH) in 5mL of N, N-Dimethylformamide (DMF) solvent, and adding 0.5mL of oleic acid and 0.25mL of oleylamine after completely dissolving to form a stable solution;
(2) And taking 750 mu L of the solution, dropwise and slowly adding the solution (the dropping speed is 10 mu L/s) into 15mL of toluene solution which is vigorously stirred, stirring at 60 ℃ for reacting for 8 hours, and precipitating to obtain the water-soluble perovskite nanocrystals P-PQDs.
(3) Separating and purifying P-PQDs perovskite nanocrystal, centrifuging the P-PQDs perovskite nanocrystal at 10000r/min for 20min, drying the obtained precipitate in an oven at 60 ℃ for 1h to obtain dark yellow powder, and making the powder green under the irradiation of a 365nm ultraviolet lamp.
(4) Dispersing the powder in water, and storing the water-soluble perovskite nanocrystalline P-PQDs at room temperature.
FIG. 2 is a transmission electron microscope image of the water-soluble P-PQDs perovskite nanocrystal prepared in example 1. As can be seen from FIG. 2, the average particle size of the P-PQDs perovskite nanocrystal is 50nm, which is larger than that of preparation example 1, and the end carboxyl polylactic acid-glycolic acid copolymer is used for coating a plurality of PQDs quantum dots into an integral shape, so that the coating effect is good.
FIG. 3 is a graph showing the fluorescence image of the P-PQDs perovskite nanocrystal of example 1 excited at 420-450 nm, and the P-PQDs perovskite nanocrystal is green under 420-450 nm excitation.
FIG. 4 is a graph showing the quantum yield of PQDs of preparation example 1 and P-PQDs perovskite nanocrystals of example 1, and the test excitation wavelength was 365.4nm. The coated P-PQDs perovskite nanocrystalline can keep high quantum yield of 88%.
FIG. 5 is a PL spectrum of the P-PQDs perovskite nanocrystals of example 1, wherein the curves in FIG. 5 represent 1, 2, 3, … … for 30 days, respectively, from top to bottom. As can be seen from the figure, the P-PQDs perovskite nanocrystal can keep higher intensity within 30 days when exposed in an aqueous system and exposed in air.
Example 2 preparation of Water-soluble perovskite nanocrystalline BioNanoprobe
In order to further couple the hydrophobic perovskite quantum dot nanocrystals with biomaterials to construct a novel nano-biological probe, on the basis of the embodiment 1, the high positive charge performance of the surfaces of the perovskite quantum dots is utilized, and the perovskite quantum dot nanocrystals are connected with the biomaterials with negative charges through the electrostatic action of the positive charges and the negative charges to construct a water-soluble perovskite nanocrystal probe, which comprises the following specific implementation steps:
(1) Chlorotoxin polypeptide (CTX) was dissolved in ultrapure water (PH = 6.42), and the solution concentration was set to 10mg/mL.
(2) 1mL of the solution of P-PQDs of example 1 with a concentration of 0.1mg/mL is mixed with 10ul of chlorotoxin polypeptide with a concentration of 10mg/mL, the mixture is vortexed for 30s to be uniformly mixed, and the prepared Probe-PQDs nanoprobe solution is stored at 4 ℃.
FIG. 6 shows fluorescence emission spectra of P-PQDs (i.e., PQDs-Water in FIG. 6) in the aqueous system of example 1 and Probe-PQDs (i.e., probe-Water in FIG. 6) as nanoprobes in example 2. As can be seen from the figure, the nanoprobe Probe-PQDs undergoes a slight blue shift relative to P-PQDs because the size of P-PQDs is changed by the attached biomaterial and the corresponding spectrum is slightly changed; meanwhile, the Probe-PQDs of the nanoprobe almost completely keep the optical performance of the original P-PQDs.
FIG. 7 is a Zeta potential diagram of the P-PQDs quantum dot nanomaterial of example 1, probe-PQDs and chlorotoxin polypeptide (CTX) of example 2.
Example 3 nanoprobes for identifying brain glioma 251 cells
After the construction of the biological nanoprobe was completed, the nanoprobe of example 2 was used for verification of the identification function. On the basis of example 2, the probe recognition function was verified by a conventional experimental method in a biological experiment. In this example, DAPI was used, the nanoprobe P-PQDs prepared in example 2 was used to label chlorotoxin polypeptides, and target analytes were brain glioma U251 cells and HA cells.
(1) U251 cells and HA cells were plated at 1X 10 per well 5 Density of individual cells seeded in a confocal dish at 37 ℃ CO 2 Culturing in an incubator.
(2) The confocal dish was removed and the cells were washed 3 times with PBS (0.01M, pH = 7.3).
(3) After fixation for 15min with 2mL of 4% paraformaldehyde, the cells were washed again 3 times with PBS (0.01M, pH = 7.3).
(4) 2mL goat serum working solution was added for blocking for 30min, and the cells were washed again 3 times with PBS (0.01M, pH = 7.3).
(5) 1mL of the prepared 0.1mg/mL Probe-PQDs Probe solution was added, and the mixture was subjected to room temperature discrimination for 1 hour.
(6) The probe solution was recovered, and the cells were washed again with PBS (0.01M, pH = 7.3) 4 to 6 times.
(7) Nuclei were counterstained with DAPI (1 mg/ml), incubated for 15min in the dark, and the cells were washed 4 to 6 times with PBS (0.01M, pH = 7.3).
(8) Confocal microscopy was observed. Two-channel excitation at 405nm and 488 nm. FIG. 8 is the Confocal fluorescence imaging chart of identification and verification of Probe-PQDs nanoprobes, glioma U251 cells and HA cells in example 3, and two-channel excitation at 405nm and 488nm is adopted. The 405nm channel corresponds to the DAPI channel; the 488nm channel corresponds to Probe-PQDs, and merge and statistical analysis are carried out. From the figure, the Probe-PQDs nanoprobe can be intuitively seen to identify the glioma U251 cell, but hardly identify the HA cell which is hardly expressed, so that the application of the nanoprobe can distinguish the tissue beside the tumor tissue cancer from the normal tissue, and can realize real-time and direct visual guidance of tumor resection.
In the invention, the aptamer or the antibody is adopted to replace the chlorotoxin polypeptide in the embodiment 2, so that the nano probe with the perovskite nanocrystal coupled with the aptamer or the antibody can be obtained, and the obtained nano probe also has a specific recognition function.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. The water-soluble quantum dot nano material is characterized by comprising quantum dots and a terminal carboxyl polylactic acid-glycolic acid copolymer coated on the surfaces of the quantum dots.
2. The water-soluble quantum dot nanomaterial according to claim 1, wherein the water-soluble quantum dot nanomaterial is a nanocrystal.
Preferably, the quantum dots have an average particle size of 5 to 20nm, preferably 10 to 15nm.
Preferably, the average particle size of the water-soluble quantum dot nano material is larger than that of the quantum dot, and is more than 5nm and less than or equal to 100nm, preferably 15-80 nm, and more preferably 50-70 nm.
3. The water-soluble quantum dot nanomaterial according to any one of claims 1-2, wherein the mass ratio (mg: mg) of the quantum dot to the carboxyl-terminated polylactic acid-glycolic acid copolymer is 116 (50-200), preferably 116 (60-150).
Preferably, the coating is a full coating or a partial coating.
Preferably, the quantum dot is a perovskite quantum dot, a carbon quantum dot, a cadmium quantum dot, a zinc sulfide quantum dot or a sulfur quantum dot.
Preferably, the perovskite quantum dot is CsPbBr 3 Calcium titaniumAnd (4) mineral quantum dots.
Preferably, the number average molecular weight of the carboxyl-terminated polylactic acid-glycolic acid copolymer is 10000 to 200000, preferably 100000 to 200000.
4. A method for preparing the water-soluble quantum dot nanomaterial as claimed in any one of claims 1 to 3, wherein the method comprises: and heating and reacting the carboxyl-terminated polylactic acid-glycolic acid copolymer with the quantum dot to obtain the water-soluble quantum dot nano material.
5. The preparation method according to claim 4, characterized in that the preparation method specifically comprises the steps of:
(A1) Mixing and dissolving raw materials for preparing quantum dots and a carboxyl-terminated polylactic acid-glycolic acid copolymer in a solvent, and adding an organic ligand to form a stable solution;
(A2) And (2) adding the stable solution obtained in the step (A1) into an anti-solvent, heating for reaction, and separating out the water-soluble quantum dot nano material by using an anti-solvent supersaturation method to prepare the water-soluble quantum dot nano material.
Preferably, the quantum dot is CsPbBr 3 When the perovskite quantum dots are prepared, the raw materials for preparing the quantum dots are CsBr and PbBr 2 。
6. A nanoprobe comprising the water-soluble quantum dot nanomaterial of any of claims 1 to 3.
Preferably, the nanoprobe is a biological material marked by the water-soluble quantum dot nanometer material.
Preferably, the biological material is selected from one, two or more of an antibody, an aptamer, a polypeptide.
7. The method of claim 6, wherein the method comprises: and coupling the water-soluble quantum dot nano material with the biological material to prepare the nano probe.
8. A kit comprising the nanoprobe of claim 6.
9. The application of the water-soluble quantum dot nano material according to any one of claims 1 to 3, the nanoprobe according to claim 6 or the kit according to claim 8 is characterized by being applied to the fields of medical detection and medical diagnosis and treatment.
Preferably, the medical test may be a cellular imaging or biological test. Preferably, brain glioma cells are imaged.
Preferably, the nanoprobe or kit is capable of recognizing at least one of the following analytes of interest: antibodies, aptamers, polypeptides, antigens, target molecules, proteases.
10. A method for identifying a target analyte, wherein the target analyte is identified using the nanoprobe of claim 7 or the kit of claim 9, the method comprising: and contacting the nano probe with the target analyte, and identifying through fluorescence detection.
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| CN116814248A (en) * | 2023-06-30 | 2023-09-29 | 常州大学 | Preparation method and application of hybridization sulfur quantum dot with room temperature afterglow |
| CN116814248B (en) * | 2023-06-30 | 2024-04-02 | 常州大学 | Preparation method and application of hybridization sulfur quantum dot with room temperature afterglow |
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