CN109912817B - Hydrogel nanoparticles for measuring ionizing radiation dose and preparation method thereof - Google Patents
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Abstract
The invention relates to the technical field of biomedical high polymer materials and ionizing radiation measurement, in particular to hydrogel nanoparticles for measuring ionizing radiation dose and a preparation method thereof. The preparation method comprises the following steps: uniformly mixing a fluorescent substance insensitive to ionizing radiation, a hydrophilic monomer, a cross-linking agent and a functional monomer in water to obtain a mixed solution; adding the mixed solution into a surfactant and n-hexane system, and carrying out inverse emulsion polymerization reaction in an inert atmosphere in the presence of an initiator and a catalyst to obtain hydrogel nanoparticles after complete reaction; activating a fluorescent substance sensitive to ionizing radiation by using an activating agent under the condition that the pH is 5.5, reacting the activated fluorescent substance with the hydrogel nanoparticles at the temperature of 4-30 ℃ under the condition that the pH is 7.4 after the activation is completed, and obtaining the hydrogel nanoparticles for measuring the dosage of the ionizing radiation after the reaction is completed.
Description
Technical Field
The invention relates to the technical field of biomedical high polymer materials and ionizing radiation measurement, in particular to hydrogel nanoparticles for measuring ionizing radiation dose and a preparation method thereof.
Background
Tumors seriously jeopardize the health and survival of humans, and radiotherapy techniques utilize ionizing radiation to treat tumors. At this stage, radiotherapy techniques have evolved rapidly, and have stepped into stages of precise positioning, precise planning, and precise treatment. However, the development of radiotherapy dosage measurement is relatively lagged, so that dosage delivery is inaccurate, serious irreversible consequences are brought to patients, and the implementation of the precise radiotherapy technology is seriously influenced.
Generally, the ionizing radiation dose measurement employs a silicon diode, a thermoluminescent dose plate, a field effect transistor, or the like. Wherein, by measuring the electron hole logarithm generated by ionizing radiation in the PN junction of the silicon diode, people can obtain the radiation dose. The material was first used for dose measurement due to its properties of real-time readout, high position resolution, high sensitivity, simple structure and reliable tare and simple readout system. In addition, the thermoluminescent dosimeter outputs and reads the absorbed ionizing radiation dose in the form of light at high temperature, so as to obtain the ionizing radiation dose value. The field effect transistor is a semiconductor type dosimeter for measuring the amount of radiation by measuring a threshold voltage change of a gate or an accumulated charge on the gate, which can be used for measurement of an accumulated dose and a dose rate, with an advantage of high accuracy.
In addition to these semiconductor materials, three-dimensional waterboxes are one of the common means of radiation therapy dosimetry measurement and verification today. In addition, the ferrous sulfate gel dosimeter measures ionizing radiation-induced oxidation of Fe3+The ion concentration is the main principle, and the relationship between the longitudinal relaxation rate and the dosage is established by utilizing magnetic resonance imaging. Professor Rege in the united states utilizes the principle that chloroauric acid is reduced into gold nanoparticles (accompanied by color change) under ionizing radiation to construct a nano hydrogel dosimeter, and utilizes an ultraviolet spectrophotometry to establish the relationship between absorbance and radiation treatment dosage. In addition to this, the present invention is,
teaching systemPreparing degradable gel coated polyvinylpyrrolidone modified Ag nano particles, generating an Ag isotope by utilizing photonuclear reaction generated by high-energy photons in the radiotherapy process, and finally establishing the relationship between the radioactivity and the dose by combining with a positron emission tomography technology.
However, the above-mentioned ionizing radiation dose measuring method has some disadvantages, such as the use of silicon diodes, which often require external circuits. The material has the defects of high dependence on ray angle, energy and dose rate, large influence of temperature and use time on the measurement sensitivity, poor tissue equivalence (the measured dose needs to be converted by a correction factor), and large measurement deviation in different batches. The thermoluminescent dose tablet has poor mechanical strength and is fragile, an additional medium is required to be fixed on the skin, the inflammation risk is increased, the influence of environment (light and heat) on the dose measurement accuracy is large, and the dose reading is complex. The field response tube has high use cost, needs external high pressure and is not suitable for in-situ dose measurement. The preparation of these dosimeters often requires complex and advanced processes, which also limits their application.
In addition, the three-dimensional water tank is large in size, low in position resolution and time-consuming to read. Fe in ferrous sulfate gel dosimeter3+Ions are easy to diffuse and have poor position resolution. The polymer gel dosimeter has a large influence on the measurement of oxygen and temperature, and the method is not sensitive to low dosage. Rege professor and
the metal-doped gel dosimeter reported by the teaching subject group has poor linear responsiveness in a low-dosage region, and the introduction of heavy metal ions reduces the tissue equivalence of the material, thereby influencing the accuracy of dosage measurement.
Disclosure of Invention
In order to solve the above technical problems, an object of the present invention is to provide a hydrogel nanoparticle for measuring an ionizing radiation dose and a method for preparing the same, wherein when the hydrogel nanoparticle of the present invention is used for measuring an ionizing radiation dose, a linear response of a colorimetric fluorescence signal and an ionizing radiation dose is in a range of 0 to 20Gy, such that the hydrogel nanoparticle has a good linear response, a low detection limit, a high detection sensitivity, a good stability of a fluorescence signal, and a low error rate.
A first object of the present invention is to provide a method for preparing hydrogel nanoparticles for measuring ionizing radiation dose, comprising the steps of:
(1) uniformly mixing a fluorescent substance insensitive to ionizing radiation, a hydrophilic monomer, a cross-linking agent and a functional monomer in water to obtain a mixed solution; wherein the fluorescent substance insensitive to ionizing radiation is selected from the group consisting of APMA-modified TAMRA, rhodamine b-isothiocyanate, rhodamine b-dextran or Texas red-dextran; the functional monomer is selected from monomers with amino;
(2) adding the mixed solution into an organic solution containing a surfactant, and carrying out inverse emulsion polymerization reaction at 20-30 ℃ in an inert atmosphere in the presence of an initiator and a catalyst to obtain hydrogel nanoparticles after complete reaction; the surface of the hydrogel nanoparticle is provided with a plurality of amino groups;
(3) activating a fluorescent substance sensitive to ionizing radiation by using an activating agent under the condition of pH 5.5, and reacting with the hydrogel nanoparticles under the condition of pH 7.4 at 4-30 ℃ (preferably 20-30 ℃) to obtain the hydrogel nanoparticles for measuring ionizing radiation dose after complete reaction; wherein the fluorescent substance sensitive to ionizing radiation is selected from fluorescent substances having a carboxyl group, an amino group or a hydroxyl group.
In the present invention, APMA represents N- (3-aminopropyl) methacrylamide hydrochloride and TAMRA represents 5(6) -carboxytetramethylrhodamine, unless otherwise specified.
Further, in the step (1), the hydrophilic monomer is selected from acrylamide (AAm), hydroxyethyl methacrylate, N-isopropylacrylamide or dimethylaminoethyl methacrylate.
Further, in the step (1), the crosslinking agent is N, N' -methylenebisacrylamide (BIS) or polyethylene glycol dimethacrylate.
Further, in step (1), the amino group-bearing monomer is selected from APMA and/or allylamine.
Further, in the step (1), the molar ratio of the ionizing radiation insensitive fluorescent substance, the hydrophilic monomer, the crosslinking agent and the functional monomer is 0.01:21:6: 8.
Further, the molar ratio of the ionizing radiation insensitive fluorescent substance in step (1) to the ionizing radiation sensitive fluorescent substance in step (3) was 0.01: 8.
Further, in step (1), the preparation method of the APMA-modified TAMRA comprises the following steps:
further, APMA and 5(6) -carboxyl tetramethyl rhodamine succinimide ester (TAMRA-SE) are mixed evenly in a buffer solution with the pH value of 9.5, and then the mixture is reacted at the temperature of 20-30 ℃ in a dark place, and the TAMRA modified by the APMA is obtained after the reaction is completed. Since TAMRA has fluorescence, APMA is modified on TAMRA, so that TAMRA has double bond functional groups capable of reacting, and the schematic diagram of the reaction is shown in FIG. 1.
Preferably, in the steps (1) to (2), the fluorescent substance insensitive to ionizing radiation is APMA modified TAMRA, which is a fluorescent substance with a double bond on the surface, the hydrophilic monomer is AAm, the crosslinking agent is BIS, and the functional monomer is APMA, and under the action of the crosslinking agent, the APMA modified TAMRA, AAm and APMA undergo emulsion copolymerization to obtain hydrogel nanoparticles with a plurality of amino groups on the surface, wherein TAMRA is polymerized into the gel matrix, and the schematic diagram of the emulsion polymerization is shown in fig. 2.
Further, in the step (2), the solvent in the organic solution is one or more of n-hexane, toluene, cyclohexane and n-heptane.
Further, in step (2), the surfactants are dodecyl poly (tetra oxyethylene) ether (Brij 30) and dioctyl sodium sulfosuccinate (AOT).
Further, in the step (2), the initiator is a persulfate; the catalyst is one or more of tetramethylethylenediamine, sodium bisulfite and urea.
Further, in the step (2), the initiator is Ammonium Persulfate (APS) and/or potassium persulfate.
Further, in the step (2), the hydrogel nanoparticles have a particle size of 40-100 nm.
Further, in step (3), the activating agents are (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS).
Further, in the step (3), the fluorescent substance sensitive to ionizing radiation is selected from coumarin 3-carboxylic acid (CCA), aminophenyl fluorescein (APF) or hydroxyphenyl fluorescein (HPF).
Preferably, the fluorescent substance sensitive to ionizing radiation is CCA, wherein carboxyl groups in the CCA react with amino groups in the hydrogel nanoparticles having amino groups on the surface to form covalent bonds, so that the CCA is attached to the surface of the hydrogel nanoparticles, and the reaction schematic diagram is shown in fig. 3.
The second object of the present invention is to provide hydrogel nanoparticles for measuring ionizing radiation dose prepared by the above preparation method, comprising hydrogel nanoparticles, a fluorescent substance sensitive to ionizing radiation attached to the surface of the hydrogel nanoparticles, and a fluorescent substance insensitive to ionizing radiation distributed in the hydrogel nanoparticles.
The fluorescent substance insensitive to ionizing radiation is connected in the hydrogel matrix by chemical bonds or is wrapped in the three-dimensional network of the hydrogel nanoparticles by physical action.
For example, when the fluorescent substance insensitive to ionizing radiation is an APMA-modified TAMRA, it is copolymerized with the hydrophilic monomer and the functional monomer by means of a double bond, so that the APMA-modified TAMRA is covalently bonded into the finally formed hydrogel matrix. When the fluorescent substance insensitive to ionizing radiation is rhodamine b-isothiocyanate, rhodamine b-dextran or texas red-dextran, it is adsorbed in the gel matrix by means of physical interaction.
When the hydrogel nanoparticles prepared by the method are used for measuring ionizing radiation dose, the fluorescence colorimetric method is adopted, and the method comprises the following steps:
(S1) irradiating the hydrogel nanogel with X rays with different ionizing radiation doses, measuring fluorescence intensity values of the hydrogel nanogel at a first emission wavelength and a second emission wavelength, then calculating the ratio of the fluorescence intensity value at the first emission wavelength to the fluorescence intensity value at the second emission wavelength, and establishing a correlation diagram between the ionizing radiation doses and the fluorescence intensity ratios;
(S2) irradiating the hydrogel nanogel with an unknown ionizing radiation dose of X rays, measuring fluorescence intensity values of the hydrogel nanogel at a first emission wavelength and a second emission wavelength, then calculating a ratio S of the fluorescence intensity value of the first emission wavelength to the fluorescence intensity value of the second emission wavelength, and finding out a specific value of the ionizing radiation dose corresponding to the ratio S according to the established correlation diagram;
wherein in the above step, the first emission wavelength is an emission wavelength of a fluorescent substance sensitive to ionizing radiation; the second emission wavelength is an emission wavelength of a fluorescent substance insensitive to ionizing radiation.
A third object of the present invention is to provide an ionizing radiation dosimeter based on colorimetric fluorescence, comprising the above hydrogel nanoparticles for measuring ionizing radiation dose.
By the scheme, the invention at least has the following advantages:
the hydrogel nanoparticles for measuring the ionizing radiation dose are prepared by an inverse emulsion polymerization method, and can be used for preparing an ionizing radiation dosimeter based on a colorimetric fluorescence method. The fluorescent colorimetric component of the hydrogel nanoparticle prepared by the invention comprises a fluorescent monomer insensitive to ionizing radiation and a fluorescent monomer sensitive to ionizing radiation, and the ionizing radiation dose can be accurately detected according to the fluorescent intensity value at the emission wavelength.
By the method, the linear response of the colorimetric fluorescence signal and the ionizing radiation dose is in the range of 0-20Gy, and the colorimetric fluorescence signal and the ionizing radiation dose have good linear response (R)20.9989). At present, the minimum detection limit of the gel dosimeter is 0.1Gy, and the detection sensitivity is 0.35Gy-1. The obtained fluorescence signal can be maintained for 20 days, has good stability in the range of 5-50 ℃ and has low error rate (1)<+/-5%) and meets the requirement of measuring the dosage of clinical radiotherapy.
The ionizing radiation dosimeter based on the colorimetric fluorescence method, which is constructed by the invention, effectively overcomes the defects of low sensitivity, poor tissue equivalence, poor linear responsiveness, difficulty in preparation and use and the like of the existing radiotherapy dosimeter, and simultaneously avoids the influence of environmental temperature, oxygen and the like on dose measurement reading.
The foregoing description is only an overview of the technical solutions of the present invention, and in order to make the technical solutions of the present invention more clearly understood and to implement them in accordance with the contents of the description, the following detailed description is given with reference to the preferred embodiments of the present invention and the accompanying drawings.
Drawings
FIG. 1 is a schematic reaction diagram of an APMA-modified TAMRA of the present invention;
FIG. 2 is a schematic diagram of hydrogel nanoparticles prepared by inverse emulsion polymerization according to example 1 of the present invention;
FIG. 3 is a schematic representation of the attachment of CCA of the present invention to the surface of a hydrogel nanoparticle;
FIG. 4 is a transmission electron micrograph and a dynamic light scattering micrograph of hydrogel nanoparticles prepared according to example 1 of the present invention;
FIG. 5 is a fluorescence colorimetric spectrum of hydrogel nanoparticles prepared in example 1 of the present invention;
FIG. 6 shows the fluorescence intensity ratio results of the hydrogel nanoparticles prepared in example 1 of the present invention at λ em-450 and 580nm under 0-20 Gy;
FIG. 7 shows the fluorescence intensity ratio results of hydrogel nanoparticles prepared in example 1 of the present invention at λ em-450 and 580nm under 0-2 Gy;
FIG. 8 shows the results of the time stability test of hydrogel nanoparticles prepared in example 1 of the present invention under different ionizing radiation doses;
FIG. 9 shows the temperature stability test results of hydrogel nanoparticles prepared in example 1 of the present invention under different ionizing radiation doses;
FIG. 10 shows the results of the error rate test of hydrogel nanoparticles prepared in example 1 of the present invention under different ionizing radiation doses;
FIG. 11 is a schematic diagram of hydrogel nanoparticles prepared by inverse emulsion polymerization according to example 2 of the present invention;
FIG. 12 is a fluorescence colorimetric spectrum of hydrogel nanoparticles prepared in example 2 of the present invention;
FIG. 13 is a dose line plot of hydrogel nanoparticles prepared according to example 2 of the present invention at 0-2 Gy;
FIG. 14 is a dose line plot of hydrogel nanoparticles prepared according to example 2 of the present invention at 0-20 Gy.
Detailed Description
The following detailed description of embodiments of the present invention is provided in connection with the accompanying drawings and examples. The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
Example 1 preparation of hydrogel nanoparticles
The embodiment provides a hydrogel nanoparticle for measuring ionizing radiation dose based on a colorimetric fluorescence method and a preparation method thereof, and the preparation method comprises the following steps:
1. 0.5mg of APMA and 1mg of TAMRA-SE were dissolved in 250. mu.L of sodium borate buffer (pH 9.5), and the resulting solution was stirred at room temperature for 24 hours in the absence of light to obtain APMA-modified TAMRA (hereinafter referred to as TAMRA-APMA), which was stored at 4 ℃ until use. The reaction scheme is shown in figure 1.
2. 300mg AAm, 180mg BIS and 300mg APMA were dissolved in 2mL deionized water, and then added to 250. mu.L of TAMRA-APMA prepared in step 1, and the mixture was filtered with a 0.2 μm filter to obtain a reaction mixture.
3. Adding 3.2mL of surfactant Brij 30 and 1.59g of AOT into 43mL of N-hexane, stirring and dissolving, and simultaneously adding 2mL of reaction mixed liquid prepared in the step 1, N2Stirring at high speed for 20min, adding 80 μ L10% APS and 60 μ L tetramethylethylenediamine, N2And reacting for 2h in the atmosphere to obtain the PAA hydrogel nano-particles modified by TAMRA. The hydrogel nanoparticles were spin-evaporated and washed with ethanol 5 times, and then freeze-dried for future use. The schematic diagram of the preparation of hydrogel nanoparticles is shown in fig. 2.
4. 10mg of CCA was dissolved in 20mL of 2- (N-morpholino) ethanesulfonic acid (MES, pH 5.5) buffer solution, and 80mg of EDC and 120mg of NHS were addedAnd (5) dissolving for 15 min. Thereafter, 20mL of the TAMRA modified PAA hydrogel nanoparticles obtained in step 3 (2.5mg mL)-120mL of 1 x phosphate buffered saline (PBS, pH 7.4)) was added thereto, and a certain amount of NaOH was added to adjust the pH 7.4 of the solution. Stirring at room temperature in a dark place for 10h, filtering with Whatman # 1 filter paper, performing rotary evaporation, washing with ethanol for 5 times, and performing freeze drying to obtain the dried TAMRA/CCA co-modified polyacrylamide nano gel. The gel is directly dispersed in water, so that the hydrogel nanoparticles for measuring the ionizing radiation dose based on the colorimetric fluorescence method can be obtained, and the fluorescent colorimetric component comprises a fluorescent monomer which is insensitive to ionizing radiation, namely 5(6) -carboxytetramethylrhodamine (lambda em-580 nm) and CCA (lambda em-450 nm) which is sensitive to ionizing radiation. Fig. 4a and b are a transmission electron microscope image and a dynamic light scattering image respectively, and it can be seen that the particle size of the nano-particles is 20-60nm, and the particle size distribution is uniform.
The hydrogel nanoparticles prepared above were irradiated with different ionizing radiation doses by an X-ray machine, the fluorescence intensity thereof was measured by an enzyme-linked immunosorbent assay, and the fluorescence colorimetric spectra at different doses are shown in fig. 5(λ ex ═ 400nm), and it can be seen that under irradiation of different ionizing radiation doses, the peak positions of the emission wavelength of the hydrogel were 450nm and 580nm, which are the emission wavelengths of CCA and 5(6) -carboxytetramethylrhodamine, respectively.
The correlation between the ionizing radiation dose and the fluorescence intensity was established according to the ratio of the fluorescence intensity at λ em 450, 580nm of the hydrogel nanoparticles prepared above at different ionizing radiation doses, and the results are shown in fig. 6 to 7. As can be seen from the figure, the linear response of the colorimetric fluorescence signal and the ionizing radiation dose is in the range of 0-20Gy, and the linear response (R) is very good20.9989), the lowest detection limit was 0.1Gy, and the detection sensitivity was 0.35Gy-1。
Meanwhile, the hydrogel nanoparticles prepared as above were irradiated with different ionizing radiation doses, and the fluorescence intensity ratios at λ em 450 and 580nm were measured at different irradiation times and different temperatures, respectively, and the results are shown in fig. 8 and 9. The result shows that the fluorescence signal obtained by the hydrogel nano-particles prepared by the method can be maintained for 20 days, and the hydrogel nano-particles also have good stability in the range of 5-50 ℃. Furthermore, the results of fig. 10 indicate that the error rate of the hydrogel nanoparticles prepared above is small at different ionizing radiation doses.
Example 2 preparation of hydrogel nanoparticles
The embodiment provides a hydrogel nanoparticle for measuring ionizing radiation dose based on a colorimetric fluorescence method and a preparation method thereof, and the preparation method comprises the following steps:
1. 1.25mg of rhodamine b-Dextran (RITC-Dextran), 300mg of AAm, 180mg of BIS and 300mg of APMA were dissolved in 2mL of deionized water, followed by filtration through a 0.2 μm filter to obtain a reaction mixture. Rhodamine b-dextran in this step can also be replaced with Texas Red-dextran or rhodamine b-isothiocyanate.
2. Adding 3.2mL of surfactant Brij 30 and 1.59g of AOT into 43mL of N-hexane, stirring and dissolving, and simultaneously adding 2mL of reaction mixed liquid prepared in the step 1, N2Stirring at high speed for 20min, adding 80 μ L10% APS and 60 μ L tetramethylethylenediamine, N2And reacting for 2h under the atmosphere to obtain the PAA-based hydrogel nanoparticles. The hydrogel nanoparticles were spin-evaporated and washed with ethanol 5 times, and then freeze-dried for future use. The schematic diagram of the preparation of hydrogel nanoparticles is shown in fig. 11 (a).
3. 10mg of CCA was dissolved in 20mL of 2- (N-morpholino) ethanesulfonic acid (MES, pH 5.5) buffer solution, and activated for 15min by adding 80mg of EDC and 120mg of NHS. Thereafter, 20mL of the TAMRA modified PAA hydrogel nanoparticles obtained in step 2 (2.5mg mL)-120mL of 1 x phosphate buffered saline (PBS, pH 7.4)) was added thereto, and a certain amount of NaOH was added to adjust the pH 7.4 of the solution. Stirring at room temperature in the dark for 10h, filtering with Whatman # 1 filter paper, rotary evaporating, washing with ethanol for 5 times, and freeze-drying to obtain dried rhodamine b-dextran/CCA co-modified polyacrylamide nano gel (FIG. 11 (b)). The hydrogel nanoparticle for measuring the ionizing radiation dose based on the colorimetric fluorescence method can be obtained by directly dispersing the gel in water.
The fluorescence colorimetric spectra of the hydrogel prepared as described above at different dosages were measured in accordance with the method of example 1, and the results are shown in fig. 12 (λ ex ═ 400nm), and it can be seen that the emission wavelength of the hydrogel under irradiation of different ionizing radiation doses had two peaks, which are the emission wavelengths of CCA and rhodamine b-dextran, respectively.
The correlation between ionizing radiation dose and fluorescence intensity was established according to the fluorescence intensity at λ em 450, 580nm of the hydrogel nanoparticles prepared above at different ionizing radiation doses, and the results are shown in fig. 13 to 14. As can be seen from the figure, the linear response of the colorimetric fluorescence signal and the ionizing radiation dose is in the range of 0-20Gy, and the linear response (R) is very good2＝0.996-0.997)。
Example 3 preparation of hydrogel nanoparticles
Hydrogel nanoparticles based on colorimetric fluorometric measurement of ionizing radiation dose were prepared as in example 1, except that AAm in step 2 could be replaced with hydroxyethyl methacrylate of equal molar mass.
Example 4 preparation of hydrogel nanoparticles
Hydrogel nanoparticles based on colorimetric fluorometric measurement of ionizing radiation dose were prepared as in example 1, except that APMA in step 2 could be replaced with allylamine of equimolar mass.
Example 5 preparation of hydrogel nanoparticles
Hydrogel nanoparticles based on colorimetric fluorometric measurement of ionizing radiation dose were prepared as in example 1, except that BIS in step 2 could be replaced with polyethylene glycol dimethacrylate of equimolar mass.
Example 6 preparation of hydrogel nanoparticles
Hydrogel nanoparticles for measuring ionizing radiation dose based on colorimetric fluorescence were prepared according to the method of example 1, except that the CCA in step 4 may be replaced with APF or HPF of equimolar mass.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, it should be noted that, for those skilled in the art, many modifications and variations can be made without departing from the technical principle of the present invention, and these modifications and variations should also be regarded as the protection scope of the present invention.
Claims (9)
1. A method of preparing hydrogel nanoparticles for measuring ionizing radiation dose, comprising the steps of: (1) uniformly mixing a fluorescent substance insensitive to ionizing radiation, a hydrophilic monomer, a cross-linking agent and a functional monomer in water to obtain a mixed solution; wherein the fluorescent substance insensitive to ionizing radiation is selected from the group consisting of APMA-modified TAMRA, rhodamine b-isothiocyanate, rhodamine b-dextran or Texas red-dextran; the functional monomer is selected from monomers with amino;
(2) adding the mixed solution into an organic solution containing a surfactant, and carrying out inverse emulsion polymerization reaction at 20-30 ℃ in an inert atmosphere in the presence of an initiator and a catalyst to obtain hydrogel nanoparticles after complete reaction; the surface of the hydrogel nanoparticle is provided with a plurality of amino groups;
(3) activating a fluorescent substance sensitive to ionizing radiation by using an activating agent under the condition that the pH is 5.5, reacting the activated fluorescent substance with the hydrogel nanoparticles at the temperature of 4-30 ℃ under the condition that the pH is 7.4 after the activation is completed, and obtaining the hydrogel nanoparticles for measuring the dosage of the ionizing radiation after the reaction is completed; wherein the fluorescent substance sensitive to ionizing radiation is selected from coumarin 3-carboxylic acid, aminophenyl fluorescein or hydroxyphenyl fluorescein.
2. The method of claim 1, wherein: in the step (1), the hydrophilic monomer is selected from acrylamide, hydroxyethyl methacrylate, N-isopropylacrylamide or dimethylaminoethyl methacrylate.
3. The method of claim 1, wherein: in step (1), the crosslinking agent is selected from N, N' -methylenebisacrylamide or polyethylene glycol dimethacrylate.
4. The method of claim 1, wherein: in step (1), the monomer having an amino group is selected from APMA and/or allyl amine.
5. The method of claim 1, wherein: in the step (2), the surfactant is dodecyl poly-tetra-oxyethylene ether and dioctyl sodium sulfosuccinate.
6. The method of claim 1, wherein: in the step (2), the initiator is persulfate; the catalyst is one or more of tetramethylethylenediamine, sodium bisulfite and urea.
7. The method of claim 1, wherein: in the step (2), the particle size of the hydrogel nano-particles is 40-100 nm.
8. A hydrogel nanoparticle for measuring an ionizing radiation dose prepared by the preparation method of any one of claims 1 to 7, wherein: the hydrogel comprises hydrogel nanoparticles, fluorescent substances sensitive to ionizing radiation and fluorescent substances insensitive to ionizing radiation, wherein the fluorescent substances sensitive to ionizing radiation are connected to the surfaces of the hydrogel nanoparticles, and the fluorescent substances insensitive to ionizing radiation are distributed in the hydrogel nanoparticles.
9. A colorimetric fluorescence-based dosimeter for ionizing radiation, comprising the hydrogel nanoparticles of claim 8 for measuring ionizing radiation dose.
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