Selenium-doped carbon dots, preparation method, and application thereof

Abstract

The present invention provides a selenium-doped carbon dot and a preparation method and application thereof, which belongs to the technical field of nano-photothermal materials. The selenium-doped carbon dots provided by the present invention include carbon dots with hydroxyl and carboxyl groups on the surface and selenium chemically bonded to the carbon skeleton of the carbon dots; the doping amount of the selenium is 10 to 50 wt%; the size of the carbon dots is 1.5 to 3.6 nm. The appropriate amount of selenium in the selenium-doped carbon dots provided by the present invention effectively improves the immune activation effect of the material; the selenium-doped carbon dot material has a continuous electron transmission channel, which makes the migration of electrons in the carbon band easier and faster, so that Se‑CDs have excellent photothermal conversion efficiency. The results of the embodiment show that the selenium-doped carbon dots Se‑CDs provided by the present invention have excellent photothermal conversion efficiency at 808 nm and 2 W / cm 2 Under the light of 10 minutes, the temperature can reach 57.5 ~ 63 ℃.

Description

Technical Field

[0001] The present invention relates to the technical field of nano-photothermal materials, and in particular to selenium-doped carbon dots, a preparation method thereof, and applications thereof. Background Art

[0002] Cancer is one of the diseases with the highest mortality rate worldwide. Although existing traditional treatments such as surgery, radiotherapy and chemotherapy have achieved certain results, their toxic side effects, treatment tolerance and tumor recurrence still seriously affect patients' prognosis.

[0003] Photothermal therapy (PTT) converts light energy into heat energy through near-infrared (NIR) irradiation, achieving precise ablation of tumor tissue. It boasts outstanding advantages such as high precision, minimal invasiveness, and high efficiency. Carbon dots (CDs), a novel class of zero-dimensional carbon nanomaterials, possess excellent optical properties, stability, and tumor targeting, and are often used as photothermal agents in PTT. While CDs exhibit certain advantages in PTT, their low biocompatibility and photothermal conversion efficiency limit their widespread use in practical applications.

[0004] Doping is an effective approach to improving the performance of carbon dots. By doping highly active elements into the carbon dot structure, not only can the photothermal properties of the carbon dots be enhanced, but new biological functions can also be imparted to them. For example, prior art discloses iron-doped carbon dots for tumor treatment, which exhibit good photothermal effects. Irradiation with 808nm light for 15 minutes can reach a temperature of 30°C. However, their photothermal conversion efficiency still does not meet the requirements of practical applications. Summary of the Invention

[0005] The present invention aims to provide selenium-doped carbon dots (Se-CDs), their preparation method, and applications. The Se-CDs provided by the present invention have excellent biocompatibility and high photothermal conversion efficiency, while effectively enhancing immune system activity.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a selenium-doped carbon dot, comprising a carbon dot having hydroxyl and carboxyl groups on the surface and selenium chemically bonded to the carbon skeleton of the carbon dot;

[0008] The doping amount of selenium is 10-50 wt%; the size of the carbon dots is 1.5-3.6 nm.

[0009] The present invention also provides a method for preparing selenium-doped carbon dots Se-CDs according to the above technical solution, comprising the following steps:

[0010] (1) citric acid, urea, sodium selenite, water, and N,N-dimethylformamide are mixed and subjected to a hydrothermal reaction to obtain a Se-CDs solution;

[0011] (2) Purifying the Se-CDs solution obtained in step (1) to obtain selenium-doped carbon dots Se-CDs.

[0012] Preferably, in step (1), the mass ratio of citric acid, urea and selenium source is (1-1.5):(1.5-2.5):(1-5).

[0013] Preferably, the selenium source in step (1) is sodium selenite, selenocysteine ​​or selenious acid.

[0014] Preferably, in step (1), the ratio of the mass of citric acid to the volume of water and the volume of N,N-dimethylformamide is 1 g: (15-20) mL: (15-20) mL.

[0015] Preferably, the temperature of the hydrothermal reaction in step (1) is 160-200° C., the heating rate of the hydrothermal reaction is 5-20° C. / min, and the time of the hydrothermal reaction is 5-8 h.

[0016] Preferably, the purification in step (2) comprises filtration, dialysis and freeze-drying performed in sequence.

[0017] Preferably, the molecular weight cut-off of the dialysis is 500 or 1000, and the dialysis time is 24 to 72 hours.

[0018] Preferably, the freeze-drying temperature is -80 to -20°C, and the freeze-drying time is 10 to 80 hours.

[0019] The present invention also provides the use of the selenium-doped carbon dots described in the above technical solution or the selenium-doped carbon dots prepared by the preparation method described in the above technical solution in the preparation of a photothermal agent.

[0020] The selenium-doped carbon dots provided by the present invention include carbon dots with hydroxyl and carboxyl groups on the surface and selenium chemically bonded to the carbon skeleton of the carbon dots; the selenium doping amount is 10-50wt%; and the size of the carbon dots is 1.5-3.6nm. The selenium-doped carbon dots provided by the present invention contain selenium, which, as an essential trace element for the human body, can effectively improve the biocompatibility of Se-CDs. At the same time, selenium is connected to the carbon skeleton in the carbon dots through chemical bonds, avoiding the toxicity problems that may be caused by free selenium and further improving the biocompatibility. The carbon skeleton in Se-CDs contains a π-conjugated structure, which optimizes the electronic structure of Se-CDs, realizes the red shift of carbon dots' light absorption, improves the light capture ability, and thus improves the light absorption ability. At the same time, the π-conjugated structure provides a continuous transmission channel for electrons, making the migration of electrons in the carbon band easier and faster, effectively improving the photothermal conversion efficiency of Se-CDs. The surface of the carbon dots has hydroxyl and carboxyl functional groups, which effectively increase the light absorption sites, further improving the light absorption ability and photothermal conversion efficiency. Selenium-doped carbon dots Se-CDs can release selenium atoms when used in photothermal reactions. Selenium atoms can effectively regulate the function of immune cells, enhance the activity of natural killer cells, and effectively improve the activity of the immune system. The results of the examples show that the selenium-doped carbon dots Se-CDs provided by the present invention have a high sensitivity and good photothermal performance at 808nm and 2W / cm 2 Under the light of 10 minutes, the temperature can reach 57.5 ~ 63 ℃. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a TEM image of the selenium-doped carbon dots in Example 1 at a magnification of 20 times;

[0022] Figure 2 This is a TEM image of the selenium-doped carbon dots of Example 1 at a magnification of 100 times;

[0023] Figure 3 This is a TEM image of the undoped carbon dots of Comparative Example 1 at a magnification of 20 times;

[0024] Figure 4 This is a diagram of the photothermal conversion efficiency of selenium-doped carbon dots in Example 1;

[0025] Figure 5 This is a graph showing the results of the selenium-doped carbon dot cytotoxicity experiment in Example 1;

[0026] Figure 6 Graph showing live and dead cell staining results of the selenium-doped carbon dots of Example 1 and the undoped carbon dots of Comparative Example 1;

[0027] Figure 7 This is a bar graph showing the effects of selenium-doped carbon dots of Example 1 and undoped carbon dots of Comparative Example 1 on natural killer cell activity;

[0028] Figure 8 This is a fluorescence staining diagram showing the effects of the selenium-doped carbon dots of Example 1 and the undoped carbon dots of Comparative Example 1 on the natural killer cell activity;

[0029] Figure 9 Graph showing the effects of selenium-doped carbon dots of Example 1 and undoped carbon dots of Comparative Example 1 in anti-tumor photothermal reactions. DETAILED DESCRIPTION

[0030] The present invention provides a selenium-doped carbon dot, comprising a carbon dot having hydroxyl and carboxyl groups on the surface and selenium chemically bonded to the carbon skeleton of the carbon dot;

[0031] The doping amount of selenium is 10-50 wt%; the size of the carbon dots is 1.5-3.6 nm.

[0032] The selenium-doped carbon dots provided by the present invention include carbon dots having hydroxyl and carboxyl groups on the surface.

[0033] In the present invention, the size of the carbon dots ranges from 1.5 to 3.6 nm, preferably from 1.8 to 3 nm, and more preferably from 2 to 2.5 nm. In the present invention, by limiting the size of the carbon dots, the specific surface area of ​​the carbon dots is increased, the active sites for light absorption are increased, and the photothermal conversion efficiency is effectively improved.

[0034] The selenium-doped carbon dots provided herein also include selenium chemically bonded to the carbon backbone of the carbon dots. In the present invention, the selenium doping amount is 10-50 wt%, preferably 20-30 wt%, and more preferably 25-28%. The chemical bond between the selenium and the carbon backbone is preferably a C-Se covalent bond. By limiting the selenium doping amount and bonding method, the biocompatibility of Se-CDs is effectively improved while avoiding overdoping that could reduce the photothermal conversion efficiency of Se-CDs.

[0035] The selenium in the selenium-doped carbon dots provided by the present invention can effectively improve their biocompatibility; the carbon dots with hydroxyl and carboxyl groups on the surface effectively increase the light absorption sites, improve the light absorption capacity and photothermal conversion efficiency, and at the same time, the selenium-doped carbon dots can release selenium atoms when used in photothermal reactions, and the selenium atoms can effectively regulate the function of immune cells, so that the obtained selenium-doped carbon dots have excellent biocompatibility and high photothermal conversion efficiency, while effectively improving the activity of the immune system.

[0036] The present invention also provides a method for preparing selenium-doped carbon dots according to the above technical solution, comprising the following steps:

[0037] (1) citric acid, urea, a selenium source, water, and N,N-dimethylformamide are mixed and subjected to a hydrothermal reaction to obtain a Se-CDs solution;

[0038] (2) Purifying the Se-CDs solution obtained in step (1) to obtain selenium-doped carbon dots.

[0039] The method comprises mixing citric acid, urea, a selenium source, water and N,N-dimethylformamide and performing a hydrothermal reaction to obtain a Se-CDs solution.

[0040] As an embodiment of the present invention, the mass ratio of citric acid, urea, and selenium source can be (1-1.5): (1.5-2.5): (1-5), or (1-1.2): (1.8-2.3): (2-4), or 1:2: (2.5-3). In the present invention, by limiting the amount ratio of the reaction raw materials, uniform mixing of the reaction raw materials is promoted, sufficient contact reaction between the raw materials is achieved, and the photothermal conversion efficiency of Se-CDs is further improved.

[0041] As an embodiment of the present invention, the selenium source can be sodium selenite, selenocysteine ​​or selenous acid, or sodium selenite. In the present invention, by limiting the type of selenium source, the reaction activity is improved and the control of subsequent reactions is facilitated.

[0042] As one embodiment of the present invention, the ratio of the mass of citric acid to the volume of water and N,N-dimethylformamide can be 2g:(15-20)mL:(15-20)mL, or 1g:(16-18)mL:(16-18)mL. In the present invention, by adding the polar aprotic solvent N,N-dimethylformamide, the reaction raw materials are effectively dissolved, further improving the mixing uniformity of the reaction raw materials; at the same time, a stable reaction environment is provided for the subsequent high-temperature reaction, further improving the performance of Se-CDs.

[0043] As an embodiment of the present invention, the mixing can be ultrasonic mixing; the power of the ultrasonic mixing can be 80-100W, or 85-90W; the time of the ultrasonic mixing can be 5-20 minutes, or 10-15 minutes. In the present invention, by limiting the process parameters of the ultrasonic treatment, the mixing uniformity of the reaction raw materials is further improved.

[0044] The present invention has no particular limitation on the ultrasonic mixing device, and any ultrasonic mixing device commonly used by those skilled in the art may be used.

[0045] As an embodiment of the present invention, the temperature of the hydrothermal reaction can be 160-200°C, 170-190°C, or 180-185°C; the heating rate of the hydrothermal reaction can be 5-20°C / min, 8-15°C / min, or 10-12°C / min; the time of the hydrothermal reaction can be 5-8h, 5.5-7h, or 6-6.5h. In the present invention, during the hydrothermal reaction, citric acid is dehydrated and carbonized at high temperature to form a carbon nanostructure, i.e., a carbon dot core; urea decomposes at high temperature to produce ammonia, providing conditions for the reduction of the selenium source; the selenium source undergoes a reduction reaction in the reducing environment produced by the ammonia to obtain selenium, and the selenium element is directly inserted into the carbon skeleton of the carbon dot through a C-Se chemical bond; by limiting the process parameters of the hydrothermal reaction, the complete progress of the hydrothermal reaction is promoted, and the photothermal conversion efficiency of Se-CDs is further improved.

[0046] As an embodiment of the present invention, after the hydrothermal reaction is completed, the reaction can be cooled and centrifuged in sequence, and the supernatant can be obtained to obtain a Se-CDs solution;

[0047] The present invention has no special limitation on the cooling, and the cooling operation commonly used by those skilled in the art may be adopted.

[0048] As an embodiment of the present invention, the centrifugal speed can be 5000-15000 rpm / min, 7000-12000 rpm / min, or 8000-10000 rpm / min; the centrifugal time can be 10-20 minutes, 12-16 minutes, or 13-15 minutes. In the present invention, by limiting the process parameters of the centrifugal process, the product separation is fully achieved and the introduction of impurities into the product is avoided.

[0049] After obtaining the Se-CDs solution, the present invention purifies the Se-CDs solution to obtain selenium-doped carbon dots.

[0050] As an embodiment of the present invention, the purification may include filtration, dialysis and freeze-drying performed in sequence.

[0051] As an embodiment of the present invention, the filtration can be membrane filtration; the pore size of the membrane can be 0.22 μm. In the present invention, by limiting the pore size of the membrane, large particles of impurities can be removed, thereby preventing the impurities from affecting product performance.

[0052] As one embodiment of the present invention, the molecular weight cut-off for dialysis can be 500 or 1000; the dialysis time can be 24 to 72 hours, 30 to 60 hours, or 48 to 55 hours. In the present invention, by limiting the parameters of the dialysis process, impurities and large aggregates in the Se-CDs solution are fully removed, which is conducive to obtaining Se-CDs of uniform size, effectively improving the stability and dispersibility of Se-CDs, and further improving the photothermal conversion efficiency of Se-CDs.

[0053] As an embodiment of the present invention, the freeze-drying temperature can be -80 to -20°C, or -70 to -40°C; and the freeze-drying time can be 10 to 80 hours, or 20 to 50 hours. In the present invention, by limiting the freeze-drying process parameters, the structural stability and optical properties of Se-CDs are ensured, further improving the photothermal conversion efficiency of Se-CDs.

[0054] The preparation method provided by the present invention can realize selenium doping of carbon dots, effectively improving the biocompatibility and photothermal conversion efficiency of Se-CDs. At the same time, the introduction of selenium into the carbon dots can effectively enhance the activity of the immune system and further improve the killing performance against tumor cells. At the same time, the preparation method is simple in steps and short in time, shortening the process.

[0055] The present invention also provides the use of the selenium-doped carbon dots described in the above technical solution or the selenium-doped carbon dots prepared by the preparation method described in the above technical solution in the preparation of a photothermal agent.

[0056] To further illustrate the present invention, the selenium-doped carbon dots Se-CDs, their preparation methods and applications provided by the present invention are described in detail below in conjunction with the examples, but they should not be construed as limiting the scope of protection of the present invention.

[0057] Example 1

[0058] A selenium-doped carbon dot, comprising a carbon dot having hydroxyl and carboxyl groups on the surface and selenium chemically bonded to the carbon skeleton of the carbon dot;

[0059] The selenium doping amount is 25wt%; the size of the carbon dots is 2.59nm;

[0060] The preparation method of selenium-doped carbon dots Se-CDs comprises the following steps:

[0061] (1) 2 g of citric acid, 4 g of urea, 2 g of sodium selenite, 15 mL of water, and 15 mL of N,N-dimethylformamide were ultrasonically mixed at 80 W for 10 min, wherein the mass ratio of citric acid, urea, and sodium selenite was 1:2:1; the volume ratio of citric acid to water and N,N-dimethylformamide was 2 g:15 mL:15 mL; after mixing, the mixture was transferred to a reactor, heated to 180 ° C at a heating rate of 10 ° C / min for hydrothermal reaction for 6 h, cooled to room temperature, centrifuged at 10000 rpm / min for 10 min, and the supernatant was collected to obtain Se-CDs solution;

[0062] (2) The Se-CDs solution obtained in step (1) was filtered through a filter membrane with a pore size of 0.22 μm. The filtered solution was dialyzed in deionized water for 24 h through a dialysis bag (molecular weight cutoff of 1000), and then freeze-dried at -70°C for 72 h to obtain selenium-doped carbon dots.

[0063] The selenium-doped carbon dots of Example 1 were detected using a transmission electron microscope, and the TEM image obtained at a magnification of 20 nm was as follows: Figure 1 As shown, the TEM image with a magnification of 5 nm is shown in Figure 2 As shown. Figures 1-2 It can be seen that the Se-doped carbon dots are evenly distributed, and the average particle size of Se-CDs is 2.59 nm with a 0.21 nm lattice corresponding to the (101) crystal plane of graphitic carbon.

[0064] Comparative Example 1

[0065] An undoped carbon dot with hydroxyl and carboxyl groups on its surface;

[0066] The method for preparing undoped carbon dots CDs comprises the following steps:

[0067] 2 g of citric acid, 4 g of urea and 30 mL of N,N-dimethylformamide were ultrasonically mixed at 80 W for 10 min, where the mass ratio of citric acid to urea was 1:2; the volume ratio of citric acid to N,N-dimethylformamide was 1 g:15 mL; after mixing, the mixture was transferred to a reactor and heated to 180 ° C at a heating rate of 10 ° C / min for hydrothermal reaction for 6 h, cooled to room temperature, centrifuged at 10000 rpm / min for 10 min, and the precipitate was taken, washed with anhydrous ethanol and freeze-dried at -70 ° C for 72 h to obtain undoped carbon dots.

[0068] The undoped carbon dots of Comparative Example 1 were detected using a transmission electron microscope, and the obtained TEM image with a magnification of 20 nm was as follows: Figure 3 As shown. Figure 3 It can be seen that the undoped carbon dots are evenly distributed, and the average particle size of CDs is 1.44 nm.

[0069] Test Example 1

[0070] The photothermal conversion efficiency of the selenium-doped carbon dots of Example 1 was tested. The specific steps were as follows: Se-CDs of Example 1 were prepared into an aqueous solution with a concentration of 400 μg / mL using water, 150 μL of which was placed in a detachable 96-well plate, and the plate was heated with a diameter of 10 mm and powers of 0.5, 1.0, 1.5, and 2 W / cm 2 , and a laser with a wavelength of 808 nm were used as light sources to irradiate a 96-well plate containing the Se-CDs solution sample of Example 1. The temperature of the sample was recorded at 30 s, 60 s, 90 s, 120 s, 3 min, 4 min, 5 min, 6 min, 7 min, 8 min, 9 min and 10 min, respectively. The results are shown in FIG. Figure 4 As shown. Figure 4 It can be seen that at 808nm, 2W / cm 2 After 10 min of light irradiation, the sample temperature can reach 63.0℃;

[0071] The cytotoxicity of the selenium-doped carbon dots of Example 1 was tested, and the specific steps were as follows: 4T1 mouse breast cancer cells were inoculated in a detachable 96-well plate, incubated at 37°C for 24 hours, and then different concentrations (100, 200, 400, and 800 μg / mL) of Se-CDs of Example 1 were added to the cells and incubated for 4 hours. The cells were washed three times with phosphate-buffered saline (PBS) to remove unbound samples; the light experimental group was exposed to 808 nm wavelength, 2.0 W / cm 2 The cells were irradiated with a high intensity for 10 min; the dark experimental group was wrapped with tin foil; 90 μL of DMEM culture medium and 10 μL of CCK8 reagent were then added to each well of the 96-well plate. After 2 h, the absorbance (OD value) at a wavelength of 450 nm was measured using a microplate reader to calculate the cell survival rate. The results were as follows: Figure 5 As shown;

[0072] Cell viability (%) = (OD sample - OD blank) / (OD control - OD blank) * 100;

[0073] The blank group contained only DMEM culture medium and CCK8 reagent, and the control group contained cells that were not treated with selenium-doped carbon dots and light according to Example 1 and were only treated with DMEM culture medium and CCK8 reagent.

[0074] from Figure 5 As can be seen, under the condition of no illumination (NIR-), the 4T1 cells co-incubated with different concentrations of Se-CDs of Example 1 all had cell viability exceeding 90%, indicating that the Se-CDs of Example 1 had no toxicity to cells and exhibited good biocompatibility;

[0075] from Figure 5 It can also be seen that under the condition of light with a wavelength of 808nm, the Se-CDs of Example 1 have a significant killing effect on tumor cells, and as the concentration of Se-CDs increases, the killing effect on tumor cells increases accordingly; when the concentration of Se-CDs reaches 800μg / ml, after 808nm light irradiation, the survival rate of 4T1 cells co-incubated with it drops to 4.5%, indicating that the selenium-doped carbon dots provided by the present invention have great potential in tumor photothermal therapy.

[0076] The live and dead cell staining experiment for the selenium-doped carbon dots of Example 1 and the undoped carbon dots of Comparative Example 1 was conducted in the following steps:

[0077] 4T1 cells were seeded into 24-well plates (5 × 10 4 The 4T1 cells were cultured at 37°C for 24 h, and the old culture medium was replaced with fresh culture medium containing 400 μg / mL CDs and Se-CDs, respectively, and incubated at 37°C for 4 h. The 4T1 cells after 24 h of culture were washed with PBS and fresh culture medium was added to serve as blank controls.

[0078] The above three culture media were irradiated at 808 nm, 2.0 W / cm 2 The three culture media were cultured in the dark for 10 minutes as the control group; acetyloxymethyl fluorescein Calcein-AM and propidium iodide PI were added to the six culture media for staining for 30 minutes and then photographed with a fluorescence microscope. The results are shown in Figure 2. Figure 6 As shown. Figure 6 It can be seen that the AM column represents the staining image after staining with Calcein-AM, the PI column represents the staining image after staining with PI, and the Merge column represents the image after merging the staining images of the AM column and the PI column; the cells incubated with PBS showed strong green fluorescence signals both in the absence of light and under light conditions, and the cells had good activity, indicating that simple light treatment could not damage tumor cells; while the cells incubated with CDs and Se-CDs had obvious green fluorescence under no light conditions, indicating good cell activity, further demonstrating that Se-CDs has good biocompatibility; under light conditions, the cells incubated with CDs and Se-CDs showed red fluorescence, indicating that the tumor cells were damaged, indicating that CDs and Se-CDs can kill tumor cells.

[0079] The immune activation performance of the selenium-doped carbon dots of Example 1 and the undoped carbon dots of Comparative Example 1 was tested in the following steps:

[0080] Six groups of 4T1 tumor-bearing mice were injected with PBS, CDs, and Se-CDs at a concentration of 10 mg / kg into their tumors. Three groups of mice were injected with PBS, CDs, and Se-CDs, respectively. The irradiation was performed at 808 nm and 1.0 W / cm 2 The experimental group received laser irradiation for 10 minutes and received photothermal therapy. Three other groups of mice, injected with PBS, CDs, and Se-CDs, were not exposed to light and served as the control group. Each group consisted of three mice. After 14 days, serum was collected from each group of mice and tumors were dissected. Serum samples were tested for levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), granzyme B (Gzms-B), and lymphocyte surface antigen CD49b using ELISA kits. The experimental results are shown in Figure 2. Figure 7 As shown. Figure 7 It can be seen that the levels of four natural killer cell (NK cell)-related immune indicators in the Se-CDs group with and without light exposure were significantly higher than those in the CDs group, indicating that NK cell activity was enhanced and Se-CDs were beneficial to improving the activity of the immune system.

[0081] The tumor tissues of the six groups of mice were subjected to immunofluorescence staining for CD49b. Figure 8 As shown. Figure 8 It can be seen that the tumor tissues in the Se-CDs groups with and without illumination (808nm) showed green fluorescence, and the levels of their immune indicators were significantly higher than those in other groups, indicating that NK cell activity was enhanced, further demonstrating that Se-CDs can effectively enhance the activity of NK cells and activate anti-tumor immunity in mice.

[0082] The tumor treatment performance of the selenium-doped carbon dots of Example 1 and the undoped carbon dots of Comparative Example 1 was tested, and the specific steps were as follows:

[0083] Six groups of 4T1 tumor-bearing mice were injected with PBS, CDs, and Se-CDs at a concentration of 10 mg / kg into their tumors. Three groups of mice injected with PBS, CDs, and Se-CDs were stimulated at 808 nm and 1.0 W / cm 2 The experimental group received laser irradiation for 10 minutes, and three groups of mice were injected with PBS, CDs, and Se-CDs respectively without light irradiation as the control group. Each group had three mice. The temperature of the tumor sites of the six groups of mice was monitored using a photothermal imager. After 14 days, the mice were killed and the tumor tissues were removed. The results are shown in the figure below. Figure 9 As shown. Figure 9 It can be seen that the tumor volume of the Se-CDs group under light conditions was significantly reduced after treatment, and the tumor volume was significantly lower than that of the other groups. The tumor of one mouse completely disappeared, further illustrating the role of Se-CDs provided by the present invention in anti-tumor photothermal reaction.

[0084] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for preparing selenium-doped carbon dots, comprising the following steps: (1) Mixing citric acid, urea, a selenium source, water, and N,N-dimethylformamide and subjecting them to a hydrothermal reaction to obtain a Se-CDs solution; (2) purifying the Se-CDs solution obtained in step (1) to obtain selenium-doped carbon dots; The temperature of the hydrothermal reaction in step (1) is 160-200°C, the heating rate of the hydrothermal reaction is 5-20°C / min, and the time of the hydrothermal reaction is 5-8h; Selenium-doped carbon dots, comprising carbon dots having hydroxyl and carboxyl groups on the surface and selenium chemically bonded to the carbon skeleton of the carbon dots; The doping amount of selenium is 10-50 wt %; the size of the carbon dots is 1.5-3.6 nm.

2. The preparation method according to claim 1, characterized in that In the step (1), the mass ratio of citric acid, urea and selenium source is 1-1.5:1.5-2.5:1-5.

3. The preparation method according to claim 1 or 2, characterized in that The selenium source in step (1) is sodium selenite, selenocysteine ​​or selenious acid.

4. The preparation method according to claim 1 or 2, characterized in that In the step (1), the ratio of the mass of citric acid to the volume of water and the volume of N,N-dimethylformamide is 2 g:15-20 mL:15-20 mL.

5. The preparation method according to claim 1, characterized in that The purification in step (2) includes filtration, dialysis and freeze-drying performed in sequence.

6. The preparation method according to claim 5, characterized in that The molecular weight cut-off of the dialysis is 500Da or 1000Da, and the dialysis time is 24 to 72 hours.

7. The preparation method according to claim 5, characterized in that The freeze-drying temperature is -80 to -20°C, and the freeze-drying time is 10 to 80 hours.

8. Use of selenium-doped carbon dots prepared by the preparation method according to any one of claims 1 to 7 in the preparation of photothermal agents.

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