Photo-thermal carbon quantum dot based on rhein as well as preparation method and application of photo-thermal carbon quantum dot

Abstract

The invention relates to the technical field of material science, in particular to a photo-thermal carbon quantum dot based on rhein as well as a preparation method and application of the photo-thermal carbon quantum dot. The method comprises the following steps: dissolving rhein and small molecule peptide in a solvent to obtain a mixed solution; performing hydrothermal reaction on the mixed solution to obtain the photo-thermal carbon quantum dots. According to the method, a one-step hydrothermal method is used as a core process, and the comprehensive advantages of being simple in process, low in energy consumption, good in batch-to-batch consistency and easy to industrialize are achieved while the high photo-thermal performance is kept; the photo-thermal carbon quantum dot based on rhein has the advantages of strong and wide light absorption capability, high photo-thermal conversion efficiency, good biocompatibility and low toxicity.

Description

Technical Field

[0001] This invention relates to the field of materials science and technology, specifically to a photothermal carbon quantum dot based on rhein, its preparation method, and its application. Background Technology

[0002] Carbon quantum dots are a new class of zero-dimensional carbon nanomaterials with dimensions smaller than 10 nm, following fullerenes, carbon nanotubes, and graphene. Composed of sp²-hybridized conjugated carbon cores and a surface rich in functional groups, they possess excellent water solubility, low toxicity, renal clearance, easily modifiable surface, tunable fluorescence / near-infrared absorption, and high photothermal conversion capabilities, making them a candidate material for next-generation photothermal agents in photothermal therapy. Photothermal therapy is a minimally invasive treatment method that uses near-infrared light (NIR, wavelength 700 nm~1100 nm) to excite a photothermal converter, converting light energy into localized high heat (42℃~48℃) to selectively kill tumor cells. Compared with traditional radiotherapy and chemotherapy, it has advantages such as strong spatiotemporal controllability, low systemic toxicity, and the ability to activate immune responses, and has become a research hotspot for adjuvant therapy of solid tumors in recent years. However, current technologies still have drawbacks such as low photothermal efficiency, poor tumor targeting, and insufficient photothermal stability in most carbon quantum dots.

[0003] Rhein is a prominent anthraquinone molecule found in the traditional Chinese medicine rhubarb, widely present in herbs such as rhubarb and Polygonum multiflorum. It possesses anti-inflammatory, antioxidant, antibacterial, and potential antitumor effects. Its advantages include effectively scavenging free radicals, inhibiting pathogenic growth, and regulating lipid metabolism. Furthermore, compared to other anthraquinone compounds, it has lower irritation and better short-term safety. However, rhein also has limitations such as poor water solubility and low bioavailability, affecting its efficacy. To further improve the clinical application of rhein, its dosage form or structure needs to be optimized to enhance safety and reduce side effects.

[0004] Using rhein as a carbon source to prepare carbon quantum dots is an effective method to overcome the aforementioned defects of rhein, achieving conjugated domain expansion and exhibiting excellent photothermal properties in the deep red-near infrared band. Compared with the visible light band, near-infrared light (700 nm~1700 nm) has a deeper tissue penetration depth, less scattering, and lower tissue autofluorescence, making it a more ideal band for applications such as bioimaging, photothermal therapy, and photodynamic therapy. Therefore, it is urgent to design a reasonable and effective preparation scheme to improve the poor water solubility and low bioavailability of rhein and to prepare carbon quantum dots with photothermal effects. In view of this, this invention provides a photothermal carbon quantum dot based on rhein, its preparation method, and its applications. Summary of the Invention

[0005] The technical problem to be solved by this invention is to provide a photothermal carbon quantum dot based on rhein, its preparation method, and its application. The purpose of this invention is to provide a composite nanomaterial based on photothermal carbon quantum dots using rhein, overcoming the shortcomings of low photothermal conversion efficiency and insufficient tumor enrichment in existing technologies. This carbon quantum dot exhibits high NIR-II region photothermal conversion efficiency and good photothermal stability.

[0006] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: In a first aspect, a method for preparing photothermal carbon quantum dots based on rhein includes the following steps: Rhein and small molecule peptides are dissolved in a solvent to obtain a mixed solution; the mixed solution is subjected to a hydrothermal reaction to obtain photothermal carbon quantum dots.

[0007] Based on the above technical solution, the present invention can be further improved as follows.

[0008] Furthermore, the small molecule peptide includes glutathione; wherein the glutathione is composed of glutamic acid, cysteine ​​and glycine linked by peptide bonds; The solvent includes ultrapure water.

[0009] Furthermore, the mass ratio of rhein to the small molecule peptide is 1:1.081; The mass ratio of rhein to solvent is 142:15~25.

[0010] Further, the process of subjecting the mixed solution to a hydrothermal reaction to obtain photothermal carbon quantum dots includes the following specific steps: subjecting the mixed solution to a hydrothermal reaction to obtain a reaction solution; subjecting the reaction solution to rotary evaporation, dialysis, and drying in sequence to obtain photothermal carbon quantum dots.

[0011] Furthermore, the conditions for the hydrothermal reaction are: temperature of 160℃~220℃, autogenous vapor pressure of 0.3 MPa~4 MPa, and time of 4 h~6 h.

[0012] Furthermore, the rotary evaporation rate is 60 r / min to 160 r / min, and the rotary evaporation is carried out until the total reaction liquid reaches about one-third of the round-bottom flask. The dialysis bag used in the dialysis process has a molecular weight cutoff of 500 Da, and the dialysis time is 24 h to 48 h. The drying process is either oven drying or freeze drying, and the instruments used are rotary evaporators, ovens, etc.

[0013] Specifically, a method for preparing photothermal carbon quantum dots of rhein includes the following specific steps: (1) Select rhein as carbon source, place the rhein in a solvent containing glutathione, stir magnetically until uniform, place the mixed solution in a polytetrafluoroethylene liner, then place the liner in a stainless steel reaction vessel, and heat and react in an electric thermostatic drying oven. (2) After the reaction is completed, the reaction solution is cooled to room temperature, collected in a round bottom flask, and subjected to rotary evaporation to separate the solvent and concentrate the reaction solution. Then, the impurities are removed by dialysis. After dialysis, a carbon quantum dot solution is obtained. The carbon quantum dot solution is dried to obtain photothermal carbon quantum dots based on rhein.

[0014] Secondly, a photothermal carbon quantum dot based on rhein, wherein the photothermal carbon quantum dot based on rhein is prepared by the aforementioned preparation method.

[0015] Furthermore, the average particle size of the photothermal carbon quantum dots based on rhein is 2 nm to 6 nm.

[0016] Thirdly, an application of photothermal carbon quantum dots based on rhein, wherein the photothermal carbon quantum dots based on rhein are used in the preparation of products for photothermal therapy or photothermal imaging.

[0017] Furthermore, the product includes any one of pharmaceuticals or reagent kits; for example, infrared thermal imaging agents, fluorescent imaging agents, etc.

[0018] The beneficial effects of this invention are: (1) Significantly reduced energy consumption and process complexity: Compared with the sol-gel method and co-precipitation method, which require secondary calcination or post-modification, the hydrothermal method adopted in this invention only needs to complete the entire process of carbonization-doping-surface passivation in a closed system at 160℃~220℃ and self-generated vapor pressure of 0.3 MPa~4 MPa, eliminating the need for high-temperature sintering and multi-step washing processes, reducing energy consumption by ≥30%, and shortening the production cycle from 12h~24h to 4h~6h.

[0019] (2) The controllability of particle size morphology is better than that of mechanical exfoliation and CVD: Compared with the quantum dots obtained by top-down mechanical exfoliation, which has a wide particle size distribution (20 nm~80 nm) and requires subsequent classification, and the CVD method, which can obtain monodisperse particles but has high requirements for substrate and atmosphere and is difficult to scale up, the hydrothermal method used in this invention can obtain uniform photothermal carbon quantum dots with an average particle size of 2 nm~6 nm and a particle size uniformity distribution PDI<0.2 by adjusting the precursor concentration, pH and reaction time. It can be directly used in biological systems without post-processing.

[0020] (3) Abundant surface functional groups, eliminating the need for secondary passivation: Compared with quantum dots obtained by microwave or combustion methods, which have a single oxygen-containing functional group on the surface and require additional passivation for stable dispersion, the water molecules in the hydrothermal system used in this invention act as both solvents and participate in the reaction, which can introduce a large amount of –COOH / –OH / –NH2 in situ. The product can be stably dispersed in the pH range of 3~11, with an absolute value of Zeta potential >30mV, and no precipitation after 90 days of storage.

[0021] (4) Green route with fewer impurities and higher purity: Compared with the coprecipitation method which easily introduces metal ion impurities and the sol-gel method which requires a large amount of organic solvent, the hydrothermal method used in this invention uses water as the only reaction medium. The by-products are only small molecule gases or soluble salts, which can be removed by one ultrafiltration. The final ash content is <0.5%, which meets the purity requirements of medical-grade carbon quantum dots.

[0022] (5) Easy to scale up and small batch-to-batch differences: Compared with the CVD method, which has a fluctuation of η > 10% after scale-up and equipment investment cost of 5 to 8 times that of the hydrothermal method, the hydrothermal reactor used in this invention can be modularly connected in series. After scale-up to 100 L, the photothermal conversion efficiency η decreases slightly from 48.2% to 47.9%, and the relative standard deviation between batches is < 3%.

[0023] (6) The present invention uses a one-step hydrothermal method as the core process, which achieves the comprehensive advantages of simple process, low energy consumption, good batch consistency and easy industrialization while maintaining high photothermal performance. The photothermal carbon quantum dots based on rhein of the present invention have strong and wide light absorption capacity, high photothermal conversion efficiency, good biocompatibility and low toxicity, as well as unique optical, structural and physicochemical properties that can be extended through surface modification. Attached Figure Description

[0024] Figure 1 Photothermal heating curves of carbon quantum dot solutions of the present invention at different concentrations are shown; where the left side shows carbon quantum dots prepared in Example 1, and the right side shows carbon quantum dots prepared in Example 2. Figure 2 The photothermal heating curve of the photothermal carbon quantum dot solution of the present invention under 808nm laser irradiation; wherein, A is the carbon quantum dot prepared in Example 1, and B is the carbon quantum dot prepared in Example 2; Figure 3 The heating-cooling curves of the carbon quantum dot solution of the present invention after four laser "on / off" cycles are shown; where A represents the carbon quantum dots prepared in Example 1 and B represents the carbon quantum dots prepared in Example 2. Figure 4 The curves are the photothermal dynamics fitting curves of the carbon quantum dots of the present invention; where A is the carbon quantum dot prepared in Example 1 and B is the carbon quantum dot prepared in Example 2. Detailed Implementation

[0025] The principles and features of this invention are described below. The examples given are for illustrative purposes only and are not intended to limit the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they should be performed according to the techniques or conditions described in the literature in this field, or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0026] The instruments and equipment used in the following embodiments are as follows: 3.5W 808nm laser (BLUEPRINT, China); handheld thermal imager (HIKMICRO-H10, China).

[0027] Example 1: Comparative Example A method for preparing photothermal carbon quantum dots based on rhein includes the following steps: Rhein was selected as the carbon source. 284.2 mg of rhein was directly dissolved in 50 mL of ultrapure water. After magnetic stirring for 10 min, the solution was placed in a polytetrafluoroethylene liner and then transferred to a 100 mL stainless steel reactor. The reactor was placed in an electric thermostatic drying oven and reacted at 180 °C for 10 h. After the reactor cooled to room temperature, the mixture was removed and transferred to a 50 mL centrifuge tube. The mixture was centrifuged at 4000 rpm for 30 min. The supernatant was collected and purified using a 500 kPa dialysis bag for 48 h. After drying, the photothermal carbon quantum dot product of rhein was obtained.

[0028] Experiment Example 2 The preparation of rhein-based carbon quantum dots using glutathione includes the following steps: Rhein was selected as the carbon source. 284.2 mg of rhein and 307.3 mg of glutathione were dissolved in 50 mL of ultrapure water. After magnetic stirring for 10 min, the solution was placed in a polytetrafluoroethylene liner and then transferred to a 100 mL stainless steel reactor. The reactor was placed in an electric thermostatic drying oven and reacted at 180 °C for 10 h. After the reactor cooled to room temperature, the mixture was removed and transferred to a 50 mL centrifuge tube. The mixture was centrifuged at 4000 rpm for 15–30 min. The supernatant was purified using a 500 Da dialysis bag for 48 h and dried to obtain the rhein-glutathione photothermal carbon quantum dot product.

[0029] Test case Weigh 20 mg of dried rhein photothermal carbon quantum dot product and rhein-glutathione photothermal carbon quantum dot product, respectively. Prepare 20 mg / mL stock solutions of rhein carbon quantum dots and rhein-glutathione photothermal carbon quantum dots using an ethanol-water solution (pure water: ethanol 3:2) as the solvent. Dilute the stock solutions with pure water to prepare 50 μg / mL, 100 μg / mL, 200 μg / mL, and 400 μg / mL rhein carbon quantum dot solutions and rhein-glutathione photothermal carbon quantum dot solutions for the following experiments: (1) Investigating the effect of carbon quantum dot solution concentration on photothermal activity: 1 mL of 50 μg / mL, 100 μg / mL, 200 μg / mL, and 400 μg / mL rhein carbon quantum dot solutions and rhein-glutathione photothermal carbon quantum dot solutions, and 1 mL of pure water (blank group) were respectively placed into 1.5 mL EP tubes. After fixation, the tubes were opened and irradiated with an 808 nm laser for 5 min. Photos were taken and recorded every 30 s. The measurements were performed in parallel three times.

[0030] The results are as follows Figure 1 As shown in the figure, higher concentrations result in greater density of photothermal active units, leading to higher heating rates and final temperatures under the same irradiation conditions. The results also indicate a positive correlation between carbon quantum dot concentration and the photothermal heating effect. This characteristic supports the precise matching of photothermal heating requirements for different applications by adjusting the carbon quantum dot concentration.

[0031] (2) Investigate the changes in carbon quantum dot solutions of the same concentration under different powers of 808nm laser irradiation: A 100 μg / mL solution of rhein carbon quantum dots and a rhein-glutathione photothermal carbon quantum dot solution were irradiated with an 808 nm laser with a power of 0 W, 0.5 W, 0.7 W, and 1.0 W, respectively, for 5 min. A photograph was taken every 30 s, and the measurements were performed in parallel three times.

[0032] The results are as follows Figure 2 As shown in Figures A and B, it can be seen that the higher the power, the higher the photothermal energy conversion efficiency per unit time, and the higher the system heating rate and final temperature. This indicates that the carbon quantum dot has significant photothermal conversion capability and can achieve controllable heating through laser triggering, meeting the core energy conversion requirements of photothermal applications.

[0033] (3) Investigating the photothermal cycling stability of carbon quantum dot solutions: A 100 μg / mL rhein carbon quantum dot solution and a rhein-glutathione photothermal carbon quantum dot solution were selected. Under the 1 W power of an 808 nm laser, which showed the best performance in (2), a near-infrared laser switch cyclic heating and cooling experiment was conducted on the rhein carbon quantum dot solution. During the heating phase of about five minutes, the solution state was recorded every 30 seconds. During the cooling phase, the solution state was recorded every time the solution temperature decreased by a gradient.

[0034] The results are as follows Figure 3 As shown in Figures A and B, the curves reveal that after multiple cycles, the "heating-cooling" trends in each cycle highly overlap, demonstrating that carbon quantum dots possess excellent cyclic stability in photothermal performance. This means that the photothermal conversion efficiency does not decrease due to repeated laser stimulation, and the thermal relaxation process (cooling) exhibits good reproducibility, supporting its repeated use in cyclic photothermal applications. (4) Investigating the photothermal conversion efficiency of carbon quantum dots: A 100 μg / mL solution of rhein-carbon quantum dots and a rhein-glutathione photothermal carbon quantum dot solution were subjected to heating and cooling experiments under irradiation with an 808 nm laser at a power of 1 W. The solution state was recorded for each temperature change gradient. The same treatment was applied to the blank group of pure water. Based on the recorded data, the photothermal response time constant τ was obtained by linear fitting with -ln(θ) (θ being the temperature-related normalization function) as the vertical axis and time as the horizontal axis. This data provides a quantitative description of the photothermal dynamics of carbon quantum dots, offering a theoretical basis for matching irradiation cycles and optimizing energy utilization efficiency in time-resolved photothermal applications (such as pulsed photothermal therapy).

[0035] Absorbance determination: 200 μL of 100 μg / mL rhein carbon quantum dot solution was placed in a 96-well plate and placed in an ELISA reader. The absorbance A of the carbon quantum dots at 808 nm was measured. The result was 0.114.

[0036] Absorbance determination: 200 μL of 100 μg / mL rhein-glutathione carbon quantum dot solution was placed in a 96-well plate and placed in an ELISA reader. The absorbance A of the carbon quantum dots at 808 nm was measured. The result was 0.102.

[0037] Since the ethanol in the solvent is largely diluted by water, it can be ignored. The photothermal conversion efficiency can be calculated using the photothermal conversion formula, as follows: (1); In equation (1), h is the heat transfer coefficient, and s is the surface area of ​​the container. It is the highest temperature the solution reaches. It is the ambient temperature. I is heat loss, I is laser power, and A is absorbance.

[0038] Use the following formula for simple conversion: (2); In formula (2) is Solution mass It is the specific heat capacity of the solution. This is the system time constant. Since the solvent mass is much greater than the solute mass, we can approximate the solution mass as the deionized mass, i.e., m = 1 g, and the solution specific heat capacity as the deionized specific heat capacity, i.e., =4.2 J / (g·℃); To calculate the system time constant, the following formula is needed: (3); (4); In equation (3), t is the cooling time, and T is the temperature at different time points during the cooling process. It is the ambient temperature. That is the highest temperature.

[0039] After conversion, the photothermal conversion efficiency can be simplified to equation (5): (5).

[0040] Linear fitting yielded a photothermal response time constant τ of rhein carbon quantum dots of 365.88. =6.2. The photothermal response time constant τ of the blank control group ultrapure water was 236.62. =2.5 ( Figure 4 Substituting the above data into equation (5), the photothermal conversion efficiency of rhein carbon quantum dots can be calculated to be 11.7%; This data enables a quantitative description of the photothermal dynamics of carbon quantum dots.

[0041] Linear fitting yielded a photothermal response time constant τ of 249.41 for rhein-glutathione photothermal carbon quantum dots. =13.2. The photothermal response time constant τ of the blank control group ultrapure water was 236.62. =2.5 ( Figure 4 Substitute the above data into equation (5). The photothermal conversion efficiency of rhein carbon quantum dots can be calculated to be 77.7%. Calculations show that the photothermal conversion efficiency of the carbon quantum dots of this invention reaches an advanced level in the industry, further confirming their potential as a highly efficient photothermal conversion material.

[0042] In summary, the concentration-dependent, power-dependent, cycling stability, and photothermal conversion efficiency of the carbon quantum dots of this invention have been systematically elucidated, providing detailed and reliable experimental evidence for their application in photothermal therapy, photothermal imaging, and other fields. This invention uses a one-step hydrothermal method as its core process, achieving a combination of advantages such as simple process, low energy consumption, good batch-to-batch consistency, and ease of industrialization while maintaining high photothermal performance. The rhein-based photothermal carbon quantum dots of this invention possess strong and broad light absorption capacity, high photothermal conversion efficiency, good biocompatibility, and low toxicity.

[0043] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A method for preparing photothermal carbon quantum dots based on rhein, characterized in that, Includes the following steps: Rhein and small molecule peptides are dissolved in a solvent to obtain a mixed solution; the mixed solution is subjected to a hydrothermal reaction to obtain photothermal carbon quantum dots.

2. The method for preparing photothermal carbon quantum dots based on rhein according to claim 1, characterized in that, The small molecule peptides include glutathione; The solvent includes ultrapure water.

3. The method for preparing photothermal carbon quantum dots based on rhein according to claim 1, characterized in that, The mass ratio of rhein to the small molecule peptide is 1:1.081; The mass ratio of rhein to solvent is 142:15~25.

4. A method for preparing photothermal carbon quantum dots based on rhein according to any one of claims 1 to 3, characterized in that, The process of obtaining photothermal carbon quantum dots by subjecting the mixed solution to a hydrothermal reaction includes the following specific steps: subjecting the mixed solution to a hydrothermal reaction to obtain a reaction solution; subjecting the reaction solution to rotary evaporation, dialysis, and drying in sequence to obtain photothermal carbon quantum dots.

5. The method for preparing photothermal carbon quantum dots based on rhein according to claim 4, characterized in that, The conditions for the hydrothermal reaction are: temperature of 160℃~220℃, autogenous vapor pressure of 0.3 MPa~4 MPa, and time of 4 h~6 h.

6. The method for preparing photothermal carbon quantum dots based on rhein according to claim 4, characterized in that, The dialysis bag used in the dialysis has a molecular weight cutoff of 500 Da, and the dialysis time is 24 h to 48 h.

7. A photothermal carbon quantum dot based on rhein, characterized in that, The photothermal carbon quantum dots based on rhein are prepared by the preparation method according to any one of claims 1 to 6.

8. The photothermal carbon quantum dot based on rhein according to claim 7, characterized in that, The average particle size of the photothermal carbon quantum dots based on rhein is 2 nm to 6 nm.

9. An application of photothermal carbon quantum dots based on rhein, characterized in that, The photothermal carbon quantum dots based on rhein as described in claim 7 are used in the preparation of products for photothermal therapy or photothermal imaging.

10. The application of photothermal carbon quantum dots based on rhein according to claim 9, characterized in that, The product includes any one of pharmaceuticals or reagent kits.

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