Modified quantum dot chlorella composite material for radiotherapy sensitization, and preparation method and application thereof

Abstract

The application belongs to the technical field of medical preparations. The application provides a modified quantum dot Chlorella polyhedral composite material for radiotherapy sensitization, a preparation method and application. The preparation method comprises the following steps: preparing a doped tungsten-chromium gallate quantum dot with a chemical formula of Zn 0.98 Ga2O4:W 0.02 6+ ,Cr 0.02 3+ ; then, the doped tungsten-chromium gallate quantum dot is modified by amination, and then modified by a polysaccharide mixture composed of alpha-maltose, cellulose and sodium alginate; finally, the doped tungsten-chromium gallate quantum dot is co-incubated with Chlorella polyhedral to obtain the modified quantum dot Chlorella polyhedral composite material. The modified quantum dot can enter Chlorella polyhedral in a large amount, and the modified quantum dot in the material obtained by the application is not easy to overflow or fall off, and is easy to preserve, compared with the prior art. Meanwhile, the material obtained by the application has a very high killing effect on CT26 cells and A549 cells at a very low dose, and the cell apoptosis rates of the two kinds of cells are both more than 80%. Therefore, the application has a high industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of medical preparation technology, specifically relating to a modified quantum dot polycholesterol composite material for radiotherapy sensitization, its preparation method, and its application. Background Technology

[0002] Currently, clinical treatments for tumors are commonly divided into invasive and non-invasive methods. However, invasive treatments such as surgery have drawbacks such as large postoperative wounds and numerous complications, which can significantly impact a patient's quality of life. Radiotherapy, on the other hand, uses high-energy X-rays or other types of radiation to destroy tumor cells. Clinically, it is considered a non-invasive treatment, and its advantages, such as high precision and significant therapeutic effects, make it suitable for treating lung cancer patients at all stages. However, due to its numerous side effects, high radiation dose, and the tendency for radiotherapy resistance caused by tumor hypoxia, the effectiveness of radiotherapy may be less pronounced.

[0003] To address the issue of ineffective radiotherapy due to hypoxia in the tumor microenvironment, anti-angiogenic drugs such as bevacizumab or lenvatinib are used clinically to remodel tumor vascular structures, increase blood perfusion, and alleviate hypoxia. In addition, nanomaterials are used to deliver oxygen or perfluorocarbon emulsions are combined with radiotherapy. However, these methods all suffer from poor biocompatibility, the equipment for large-scale production of nanomaterials is expensive, and there are even risks of allergic reactions and embolism.

[0004] In the preparation of antitumor agents, in addition to nanomaterials, microorganisms are also used as drug carriers. However, to the inventor's knowledge, there are very few reports on combining microorganisms with common biomedical materials (such as quantum dots) as radiosensitizers in the preparation of radiosensitizing medical materials. The very few reports that attach quantum dots to the surface of bacteria have drawbacks such as poor sensitization effect, high required radiation dose, and easy detachment of quantum dots, making the sensitizer difficult to preserve. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide a chemosensitizing medical material prepared with the participation of microorganisms, which can have a high killing effect on tumor cells at an extremely low dose of 1 Gy.

[0006] To achieve the above-mentioned technical objectives, the present invention provides the following technical solution:

[0007] A method for preparing a modified quantum dot *Pyrophyllum commune* composite material for radiotherapy sensitization, the method comprising the following steps:

[0008] (1) Preparation of Zn 0.98 Ga2O4:W 0.026+ ,Cr 0.02 3+ Zinc gallate quantum dots doped with tungsten and chromium;

[0009] (2) The obtained zinc gallate quantum dots doped with tungsten chromium were modified by amination using a solvent composed of N,N-dimethylformamide and 3-aminopropyltriethoxysilane to obtain amination quantum dots;

[0010] (3) The obtained aminated quantum dots and polysaccharide mixture are placed in water and reacted at 70-80℃. After the reaction is completed, the mixture is centrifuged and the unreacted polysaccharide is washed away. Then it is dried to obtain modified quantum dots. The polysaccharide mixture is composed of α-maltose, cellulose and sodium alginate in a weight ratio of 4:2:1.

[0011] (4) The modified quantum dots and Synechococcus are co-incubated in a culture medium under light conditions to obtain the modified quantum dot Synechococcus composite material.

[0012] Preferably, the zinc gallate quantum dots doped with tungsten and chromium are prepared using Ga(NO3)3·xH2O, Zn(NO3)2·6H2O, Na2WO4·2H2O and Cr(NO3)3·9H2O as raw materials.

[0013] Preferably, the weight ratio of Ga(NO3)3·xH2O, Zn(NO3)2·6H2O, Na2WO4·2H2O and Cr(NO3)3·9H2O is 500:320:10:5.

[0014] Preferably, the method used in preparing the tungsten-chromium-doped zinc gallate quantum dots in step (1) is as follows: 5.0g Ga(NO3)3·xH2O, 3.2g Zn(NO3)2·6H2O, 0.1g Na2WO4·2H2O and 0.05g Cr(NO3)3·9H2O are prepared as raw materials and dissolved in 100 mL of deionized water. The pH is adjusted to 9 and stirred for 30 minutes. The solution is transferred to a hydrothermal reactor and reacted at 180°C for 4 hours. After the reaction, the mixture is centrifuged, washed and dried to obtain the precursor powder. The precursor powder is calcined at 700°C for 3 hours to obtain the final product.

[0015] Preferably, in a solvent composed of N,N-dimethylformamide and 3-aminopropyltriethoxysilane, the volume ratio of N,N-dimethylformamide to 3-aminopropyltriethoxysilane is 125:1.

[0016] Preferably, the method used in preparing the amination quantum dots in step (2) is as follows: 5 mg of zinc gallate quantum dots doped with tungsten and chromium are added to a solvent consisting of 10 mL of N,N-dimethylformamide and 80 μL of 3-aminopropyltriethoxysilane, stirred for 15 minutes to mix evenly, and then heated and stirred in a water bath at 85°C for 12 hours on a magnetically heated stirrer; then the solution after reaction is centrifuged at 10,000 rpm for 10 minutes and washed 3 times with deionized water to obtain the final product.

[0017] Preferably, the method used in preparing the modified quantum dots in step (3) is as follows: weigh 20 mg of the aminated quantum dots obtained in step (2) and a polysaccharide mixture composed of 20 mg α-maltose, 10 mg cellulose and 5 mg sodium alginate, dissolve them separately in 20 mL of deionized water and stir for 15 minutes, then mix the two solutions evenly; heat and stir the reaction in a water bath at 70°C for 12 hours on a magnetic stirrer to obtain a milky white solution; then centrifuge at 10000 rpm for 10 minutes, wash with deionized water 3 times, and finally dry for 6 hours to obtain the final product.

[0018] Preferably, in step (4), the method used to prepare the modified quantum dot polycholesterol composite material is as follows: take 20 mg of the modified quantum dots obtained in step (3) and mix them with 100 mL of cyanobacterial solution in logarithmic phase using BG11 medium as solvent, and place them in a shaker at 100 rpm / min and incubate them together at 3000 lux light intensity for 1 hour; then centrifuge at 3000 rpm for 3 minutes to obtain a green precipitate, and then dissolve the obtained precipitate in PBS solution.

[0019] A modified quantum dot polychondrium composite material for radiotherapy sensitization, the composite material being prepared by the aforementioned preparation method.

[0020] The aforementioned modified quantum dot polychondrium composite material for radiotherapy sensitization is used in the preparation of radiotherapy sensitizers for tumor treatment.

[0021] The beneficial effects of this invention are:

[0022] This invention provides a modified quantum dot-based Synechococcus composite material for radiotherapy sensitization. This material allows for the large-scale incorporation of modified quantum dots into Synechococcus, and compared to existing technologies, the modified quantum dots in the material obtained by this invention are less prone to leakage or detachment, making it easier to store. Furthermore, the material obtained by this invention exhibits extremely high killing effects on both CT26 and A549 cells at very low doses, with apoptosis rates exceeding 80% for both cell types. Therefore, this invention has high potential for industrial application. Attached Figure Description

[0023] Figure 1This is a TEM image of the zinc gallate quantum dots doped with tungsten chromium obtained in Example 1;

[0024] Figure 2 The image shows the detection results of the excitation and emission wavelengths of the tungsten-chromium-doped zinc gallate quantum dots obtained in Example 1.

[0025] Figure 3 This is a transmission electron microscopy (TEM) image showing the endocytosis of the modified quantum dots prepared by Synechococcus by Synechococcus. Detailed Implementation

[0026] The present invention will be specifically described below through embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the above-described invention are still within the scope of protection of the present invention.

[0027] Example 1

[0028] Preparation of modified quantum dot *Pyrophyllum commune* composite material for radiotherapy sensitization:

[0029] 1. Raw material preparation

[0030] According to the chemical formula Zn 0.98 Ga2O4:W 0.02 6+ ,Cr 0.02 3+ Weigh the raw materials:

[0031] Ga(NO3)3·xH2O: 5.0g, Zn(NO3)2·6H2O: 3.2 g, Na2WO4·2H2O: 0.1 g, Cr(NO3)3·9H2O: 0.05 g.

[0032] 2. Preparation of zinc gallate quantum dots doped with tungsten and chromium

[0033] Dissolve the raw material prepared in step 1 in 100 mL of deionized water, adjust the pH to 9, and stir for 30 minutes; transfer the solution to a hydrothermal reactor and react at 180°C for 4 hours; after the reaction is completed, centrifuge, wash, and dry to obtain precursor powder; calcine the precursor powder at 700°C for 3 hours.

[0034] 3. Preparation of amination quantum dots

[0035] Add 5 mg of the tungsten-chromium-doped zinc gallate quantum dots obtained in step 2 to a solvent consisting of 10 mL of N,N-dimethylformamide and 80 μL of 3-aminopropyltriethoxysilane. Stir for 15 minutes to mix evenly, and then heat and stir in a water bath at 85°C for 12 hours using a magnetic stirrer. Then centrifuge the reaction solution at 10,000 rpm for 10 minutes and wash it three times with deionized water to obtain the final product.

[0036] 4. Preparation of polysaccharide-modified quantum dots

[0037] Weigh 20 mg of the aminated quantum dots obtained in step 3 and the polysaccharide mixture consisting of 20 mg α-maltose, 10 mg cellulose and 5 mg sodium alginate. Dissolve each in 20 mL of deionized water and stir for 15 minutes. Then mix the two solutions thoroughly. Heat and stir the mixture in a water bath at 70 °C for 12 hours to obtain a milky white solution. Centrifuge at 10,000 rpm for 10 minutes, wash three times with deionized water, and finally dry for 6 hours to obtain a powdered product.

[0038] 5. Preparation of modified quantum dot polysaccharide composite materials

[0039] Take 20 mg of the modified quantum dots obtained in step 4 and mix them with 100 mL of cyanobacterial solution in logarithmic phase using BG11 medium as solvent. Place the mixture in a shaker at 100 rpm / min and incubate it together at 3000 lux light intensity for 1 hour. Then, centrifuge at 3000 rpm for 3 minutes to obtain a green precipitate. Dissolve the precipitate in PBS solution.

[0040] Example 2

[0041] Except for the hydrothermal reaction temperature of 220°C in step 2, the rest is the same as in Example 1.

[0042] Example 3

[0043] Except for the hydrothermal reaction temperature of 200°C in step 2, the rest is the same as in Example 1.

[0044] Comparative Example 1

[0045] Compared with Example 1, this comparative example uses α-maltose to replace the polysaccharide mixture in Example 1 when preparing modified quantum dots, while the rest remains the same as in Example 1. The specific technical solution of this comparative example is as follows:

[0046] 1. Raw material preparation

[0047] According to the chemical formula Zn 0.98 Ga2O4:W 0.02 6+ ,Cr0.02 3+ Weigh the raw materials:

[0048] Ga(NO3)3·xH2O: 5.0g, Zn(NO3)2·6H2O: 3.2 g, Na2WO4·2H2O: 0.1 g, Cr(NO3)3·9H2O: 0.05 g.

[0049] 2. Preparation of zinc gallate quantum dots doped with tungsten and chromium

[0050] Dissolve the raw material prepared in step 1 in 100 mL of deionized water, adjust the pH to 9, and stir for 30 minutes; transfer the solution to a hydrothermal reactor and react at 180°C for 4 hours; after the reaction is completed, centrifuge, wash, and dry to obtain precursor powder; calcine the precursor powder at 700°C for 3 hours.

[0051] 3. Preparation of amination quantum dots

[0052] Add 5 mg of the tungsten-chromium-doped zinc gallate quantum dots obtained in step 2 to a solvent consisting of 10 mL of N,N-dimethylformamide and 80 μL of 3-aminopropyltriethoxysilane. Stir for 15 minutes to mix evenly, and then heat and stir in a water bath at 85°C for 12 hours using a magnetic stirrer. Then centrifuge the reaction solution at 10,000 rpm for 10 minutes and wash it three times with deionized water to obtain the final product.

[0053] 4. Preparation of polysaccharide-modified quantum dots

[0054] Weigh 20 mg of the amination quantum dots obtained in step 3 and 35 mg of α-maltose, dissolve them separately in 20 mL of deionized water and stir for 15 minutes, then mix the two solutions evenly; heat and stir the reaction in a water bath at 70 °C for 12 hours on a magnetic stirrer to obtain a milky white solution; then centrifuge at 10000 rpm for 10 minutes, wash three times with deionized water, and finally dry for 6 hours to obtain a powdered product.

[0055] 5. Preparation of modified quantum dot polysaccharide composite materials

[0056] Take 20 mg of the modified quantum dots obtained in step 4 and mix them with 100 mL of cyanobacterial solution in logarithmic phase using BG11 medium as solvent. Place the mixture in a shaker at 100 rpm / min and incubate it together at 3000 lux light intensity for 1 hour. Then, centrifuge at 3000 rpm for 3 minutes to obtain a green precipitate. Dissolve the precipitate in PBS solution.

[0057] Comparative Example 2

[0058] Compared to Example 1, this comparative example uses cellulose to replace the polysaccharide mixture in Example 1 when preparing modified quantum dots, while remaining the same as Example 1. The specific technical solution of this comparative example is as follows:

[0059] 1. Raw material preparation

[0060] According to the chemical formula Zn 0.98 Ga2O4:W 0.02 6+ ,Cr 0.02 3+ Weigh the raw materials:

[0061] Ga(NO3)3·xH2O: 5.0g, Zn(NO3)2·6H2O: 3.2 g, Na2WO4·2H2O: 0.1 g, Cr(NO3)3·9H2O: 0.05 g.

[0062] 2. Preparation of zinc gallate quantum dots doped with tungsten and chromium

[0063] Dissolve the raw material prepared in step 1 in 100 mL of deionized water, adjust the pH to 9, and stir for 30 minutes; transfer the solution to a hydrothermal reactor and react at 180°C for 4 hours; after the reaction is completed, centrifuge, wash, and dry to obtain precursor powder; calcine the precursor powder at 700°C for 3 hours.

[0064] 3. Preparation of amination quantum dots

[0065] Add 5 mg of the tungsten-chromium-doped zinc gallate quantum dots obtained in step 2 to a solvent consisting of 10 mL of N,N-dimethylformamide and 80 μL of 3-aminopropyltriethoxysilane. Stir for 15 minutes to mix evenly, and then heat and stir in a water bath at 85°C for 12 hours using a magnetic stirrer. Then centrifuge the reaction solution at 10,000 rpm for 10 minutes and wash it three times with deionized water to obtain the final product.

[0066] 4. Preparation of polysaccharide-modified quantum dots

[0067] Weigh 20 mg of the aminated quantum dots obtained in step 3 and 35 mg of cellulose, dissolve them separately in 20 mL of deionized water and stir for 15 minutes, then mix the two solutions evenly; heat and stir the reaction in a water bath at 70 °C for 12 hours on a magnetic stirrer to obtain a milky white solution; then centrifuge at 10000 rpm for 10 minutes, wash three times with deionized water, and finally dry for 6 hours to obtain a powdered product.

[0068] 5. Preparation of modified quantum dot polysaccharide composite materials

[0069] Take 20 mg of the modified quantum dots obtained in step 4 and mix them with 100 mL of cyanobacterial solution in logarithmic phase using BG11 medium as solvent. Place the mixture in a shaker at 100 rpm / min and incubate it together at 3000 lux light intensity for 1 hour. Then, centrifuge at 3000 rpm for 3 minutes to obtain a green precipitate. Dissolve the precipitate in PBS solution.

[0070] Comparative Example 3

[0071] Compared with Example 1, this comparative example uses sodium alginate to replace the polysaccharide mixture in Example 1 when preparing modified quantum dots, while the rest remains the same as in Example 1. The specific technical solution of this comparative example is as follows:

[0072] 1. Raw material preparation

[0073] According to the chemical formula Zn 0.98 Ga2O4:W 0.02 6+ ,Cr 0.02 3+ Weigh the raw materials:

[0074] Ga(NO3)3·xH2O: 5.0g, Zn(NO3)2·6H2O: 3.2 g, Na2WO4·2H2O: 0.1 g, Cr(NO3)3·9H2O: 0.05 g.

[0075] 2. Preparation of zinc gallate quantum dots doped with tungsten and chromium

[0076] Dissolve the raw material prepared in step 1 in 100 mL of deionized water, adjust the pH to 9, and stir for 30 minutes; transfer the solution to a hydrothermal reactor and react at 180°C for 4 hours; after the reaction is completed, centrifuge, wash, and dry to obtain precursor powder; calcine the precursor powder at 700°C for 3 hours.

[0077] 3. Preparation of amination quantum dots

[0078] Add 5 mg of the tungsten-chromium-doped zinc gallate quantum dots obtained in step 2 to a solvent consisting of 10 mL of N,N-dimethylformamide and 80 μL of 3-aminopropyltriethoxysilane. Stir for 15 minutes to mix evenly, and then heat and stir in a water bath at 85°C for 12 hours using a magnetic stirrer. Then centrifuge the reaction solution at 10,000 rpm for 10 minutes and wash it three times with deionized water to obtain the final product.

[0079] 4. Preparation of polysaccharide-modified quantum dots

[0080] Weigh 20 mg of the aminated quantum dots obtained in step 3 and 35 mg of sodium alginate, dissolve them separately in 20 mL of deionized water and stir for 15 minutes, then mix the two solutions evenly; heat and stir the reaction in a water bath at 70 °C for 12 hours on a magnetic stirrer to obtain a milky white solution; then centrifuge at 10000 rpm for 10 minutes, wash three times with deionized water, and finally dry for 6 hours to obtain a powdered product.

[0081] 5. Preparation of modified quantum dot polysaccharide composite materials

[0082] Take 20 mg of the modified quantum dots obtained in step 4 and mix them with 100 mL of cyanobacterial solution in logarithmic phase using BG11 medium as solvent. Place the mixture in a shaker at 100 rpm / min and incubate it together at 3000 lux light intensity for 1 hour. Then, centrifuge at 3000 rpm for 3 minutes to obtain a green precipitate. Dissolve the precipitate in PBS solution.

[0083] Comparative Example 4

[0084] Compared to Example 1, this comparative example uses a polysaccharide mixture of α-maltose and cellulose to replace the polysaccharide mixture in Example 1 when preparing modified quantum dots; otherwise, it remains the same as Example 1. The specific technical solution of this comparative example is as follows:

[0085] 1. Raw material preparation

[0086] According to the chemical formula Zn 0.98 Ga2O4:W 0.02 6+ ,Cr 0.02 3+ Weigh the raw materials:

[0087] Ga(NO3)3·xH2O: 5.0g, Zn(NO3)2·6H2O: 3.2 g, Na2WO4·2H2O: 0.1 g, Cr(NO3)3·9H2O: 0.05 g.

[0088] 2. Preparation of zinc gallate quantum dots doped with tungsten and chromium

[0089] Dissolve the raw material prepared in step 1 in 100 mL of deionized water, adjust the pH to 9, and stir for 30 minutes; transfer the solution to a hydrothermal reactor and react at 180°C for 4 hours; after the reaction is completed, centrifuge, wash, and dry to obtain precursor powder; calcine the precursor powder at 700°C for 3 hours.

[0090] 3. Preparation of amination quantum dots

[0091] Add 5 mg of the tungsten-chromium-doped zinc gallate quantum dots obtained in step 2 to a solvent consisting of 10 mL of N,N-dimethylformamide and 80 μL of 3-aminopropyltriethoxysilane. Stir for 15 minutes to mix evenly, and then heat and stir in a water bath at 85°C for 12 hours using a magnetic stirrer. Then centrifuge the reaction solution at 10,000 rpm for 10 minutes and wash it three times with deionized water to obtain the final product.

[0092] 4. Preparation of polysaccharide-modified quantum dots

[0093] Weigh 20 mg of the aminated quantum dots obtained in step 3 and a polysaccharide mixture consisting of 20 mg of α-maltose and 15 mg of cellulose. Dissolve each in 20 mL of deionized water and stir for 15 minutes. Then mix the two solutions thoroughly. Heat and stir the mixture in a water bath at 70 °C for 12 hours to obtain a milky white solution. Centrifuge at 10,000 rpm for 10 minutes, wash three times with deionized water, and finally dry for 6 hours to obtain a powdered product.

[0094] 5. Preparation of modified quantum dot polysaccharide composite materials

[0095] Take 20 mg of the modified quantum dots obtained in step 4 and mix them with 100 mL of cyanobacterial solution in logarithmic phase using BG11 medium as solvent. Place the mixture in a shaker at 100 rpm / min and incubate it together at 3000 lux light intensity for 1 hour. Then, centrifuge at 3000 rpm for 3 minutes to obtain a green precipitate. Dissolve the precipitate in PBS solution.

[0096] Comparative Example 5

[0097] Compared with Example 1, this comparative example does not use polysaccharide-modified quantum dots, but is otherwise the same as Example 1. The specific technical solution of this comparative example is as follows:

[0098] 1. Raw material preparation

[0099] According to the chemical formula Zn 0.98 Ga2O4:W 0.02 6+ ,Cr 0.02 3+ Weigh the raw materials:

[0100] Ga(NO3)3·xH2O: 5.0g, Zn(NO3)2·6H2O: 3.2 g, Na2WO4·2H2O: 0.1 g, Cr(NO3)3·9H2O: 0.05 g.

[0101] 2. Preparation of zinc gallate quantum dots doped with tungsten and chromium

[0102] Dissolve the raw material prepared in step 1 in 100 mL of deionized water, adjust the pH to 9, and stir for 30 minutes; transfer the solution to a hydrothermal reactor and react at 180°C for 4 hours; after the reaction is completed, centrifuge, wash, and dry to obtain precursor powder; calcine the precursor powder at 700°C for 3 hours.

[0103] 3. Preparation of amination quantum dots

[0104] Add 5 mg of the tungsten-chromium-doped zinc gallate quantum dots obtained in step 2 to a solvent consisting of 10 mL of N,N-dimethylformamide and 80 μL of 3-aminopropyltriethoxysilane. Stir for 15 minutes to mix evenly, and then heat and stir in a water bath at 85°C for 12 hours using a magnetic stirrer. Then, centrifuge the reaction solution at 10,000 rpm for 10 minutes, wash it three times with deionized water, and finally dry it for 6 hours to obtain a powdered product.

[0105] 4. Preparation of modified quantum dot polysaccharide composite materials

[0106] Take 20 mg of the aminated quantum dots obtained in step 3 and mix them with 100 mL of cyanobacterial solution in logarithmic phase using BG11 medium as solvent. Place the mixture in a shaker at 100 rpm / min and incubate it together at 3000 lux light intensity for 1 hour. Then, centrifuge at 3000 rpm for 3 minutes to obtain a green precipitate. Dissolve the precipitate in PBS solution.

[0107] Comparative Example 6

[0108] Compared with Example 1, except that the tungsten-chromium-doped zinc gallate quantum dots were replaced with chromium-doped zinc gallate quantum dots, the rest were the same as in Example 1. The preparation method of the chromium-doped zinc gallate quantum dots was in accordance with the method described in the literature "Preparation of near-infrared chemiluminescent nanoprobes based on chromium ion-doped zinc gallate and its hydrogen peroxide sensing study" (Feng Yang, Yang Xinyi, Rao Qianli, et al. Preparation of near-infrared chemiluminescent nanoprobes based on chromium ion-doped zinc gallate and its hydrogen peroxide sensing study [J]. Science in China: Chemistry, 2024, 54(10):1869-1876.), and the calcination temperature of 700℃ was selected.

[0109] Experimental Example 1

[0110] The excitation and emission wavelengths of the tungsten-chromium-doped zinc gallate quantum dots obtained in Example 1 were detected, and the experimental results are as follows: Figure 2 As shown. By Figure 2 From Part A, it can be seen that the excitation wavelength of the obtained tungsten-chromium-doped zinc gallate quantum dots is 347 nm, and the emission wavelength is 695 nm. Figure 2As shown in Part B, under different doses of X-ray excitation, the tungsten-chromium-doped zinc gallate quantum dots emitted visible light with a wavelength of 696 nm, providing the necessary light source for the subsequent photosynthesis of the modified quantum dot Synechococcus composite material.

[0111] The particle size and morphology of the tungsten-chromium-doped zinc gallate quantum dots obtained in Example 1 were measured and observed. The particle size was approximately 8 nm, and the morphology was as follows. Figure 1 The TEM results are shown in the image.

[0112] Experiment Example 2

[0113] The endocytosis of modified quantum dots in the modified quantum dot *Symplocos globosum* composite materials obtained in Example 1 and Comparative Examples 1-6 was observed and counted using transmission electron microscopy. Under random field of view, the endocytosis of modified quantum dots in 100 *Symplocos globosum* samples was observed, and then the number of modified quantum dots in each sample was counted and calculated as a whole. Figure 3 As shown, in the composite material prepared in Example 1 with a polysaccharide modification step, the modified quantum dots were successfully incorporated into Synechococcus.

[0114] As shown in Table 1, in the composite material obtained without the polysaccharide modification step (i.e., the material obtained in Comparative Example 5), there were fewer than 10 modified quantum dots per 100 *Synechococcus* cells, indicating that the polysaccharide modification step is crucial for the entry of quantum dots into *Synechococcus*. Furthermore, when modified quantum dots obtained by using only a single polysaccharide or a mixture of two polysaccharides were co-incubated with *Synechococcus*, the number of modified quantum dots that could enter the *Synechococcus* was relatively small. This suggests that modification with a mixed polysaccharide composed of maltose, cellulose, and sodium alginate helps to improve the endocytosis of quantum dots by *Synechococcus*.

[0115] Table 1

[0116]

[0117] Note: In Table 1, "-" indicates a value less than 0.1.

[0118] Experimental Example 3

[0119] The modified quantum dot *Symplocos globosum* composite material obtained in Example 1 was subjected to cell compatibility testing. Specifically, 8000 BEAS-2B cells per well were respectively mixed with 10... 4 10 5 10 6 10 7 After co-incubating engineered Synechococcus (i.e., modified quantum dot Synechococcus composite material) with CFU / mL for 24 hours, cell viability was detected using the CCK8 kit, and the cell viability was found to be above 95%.

[0120] Experiment Example 4

[0121] The modified quantum dot *Symplocos globosum* composite materials obtained in Example 1 and Comparative Examples 1-6 were co-incubated with CT26 tumor cells and A549 tumor cells, respectively, under normoxic conditions for 6 hours, and then irradiated with 1 Gy X-rays for 1 minute. The apoptosis rate was calculated. The control group was treated with irradiation alone. The experimental results are shown in Table 2.

[0122] As shown in Table 2, the modified quantum dot *Symplocos globosum* composite material for radiotherapy sensitization obtained in this invention exhibits excellent sensitization effects for radiotherapy. At extremely low doses (1 Gy), it demonstrates extremely high killing effects on both CT26 and A549 cells, with apoptosis rates exceeding 80% for both cell types. Combining Tables 1 and 2, it can be seen that the number of internalized modified quantum dots by *Symplocos globosum* significantly affects the sensitization effect of the resulting engineered *Symplocos globosum* (i.e., the modified quantum dot *Symplocos globosum* composite material) on radiotherapy.

[0123] Table 2

[0124]

Claims

1. A method for preparing a modified quantum dot Chlorella polykrikoides composite material for radiotherapy sensitization, characterized in that, The preparation method comprises the following steps: (1) Preparation of zinc gallate quantum dots of the chemical formula Zn 0.98 Ga2O4:W 0.02 6+ ,Cr 0.02 3+ doped with tungsten and chromium (2) The obtained tungsten-chromium-doped zinc gallate quantum dots are subjected to amination modification by using a solvent composed of N,N-dimethylformamide and 3-aminopropyl triethoxysilane, so as to obtain aminated quantum dots; (3) The obtained aminated quantum dots and a polysaccharide mixture are placed in water and reacted at 70-80 DEG C, after the reaction is completed, centrifugal separation is performed and unreacted polysaccharide is washed away, and then drying is performed, so as to obtain modified quantum dots; the polysaccharide mixture is composed of alpha-maltose, cellulose and sodium alginate at a weight ratio of 4:2:1; (4) The obtained modified quantum dots and Chlorella are co-incubated in a culture medium under light, so as to obtain the modified quantum dot Chlorella composite material.

2. The method for preparing a modified quantum dot Chlorella polykrikoides composite material for radiotherapy sensitization according to claim 1, characterized in that, In the preparation of the tungsten-chromium-doped zinc gallate quantum dots, Ga(NO3)3xH2O, Zn(NO3)2 6H2O, Na2WO4 2H2O and Cr(NO3)3 9H2O are used as raw materials.

3. The method for preparing a modified quantum dot Chlorella polykrikoides composite material for radiotherapy sensitization according to claim 2, characterized in that, The weight ratio of the Ga(NO3)3xH2O, Zn(NO3)2 6H2O, Na2WO4 2H2O and Cr(NO3)3 9H2O is 500:320:10:

5.

4. The method for preparing a modified quantum dot Chlorella polykrikoides composite material for radiotherapy sensitization according to claim 3, characterized in that, In the preparation of the tungsten-chromium-doped zinc gallate quantum dots in step (1), 5.0 g of Ga(NO3)3xH2O, 3.2 g of Zn(NO3)2 6H2O, 0.1 g of Na2WO4 2H2O and 0.05 g of Cr(NO3)3 9H2O are prepared as raw materials, and the raw materials are dissolved in 100 mL of deionized water, the pH is adjusted to 9, and stirring is performed for 30 minutes; the solution is transferred to a hydrothermal reaction kettle, and reaction is performed at 180 DEG C for 4 hours; after the reaction is completed, centrifugal separation is performed, washing is performed, and drying is performed to obtain a precursor powder; the precursor powder is calcined at 700 DEG C for 3 hours, and the tungsten-chromium-doped zinc gallate quantum dots are obtained.

5. The method for preparing a modified quantum dot Chlorella polykrikoides composite material for radiotherapy sensitization according to claim 1, characterized in that, In the solvent composed of N,N-dimethylformamide and 3-aminopropyl triethoxysilane, the volume ratio of N,N-dimethylformamide to 3-aminopropyl triethoxysilane is 125:

1.

6. The method for preparing a modified quantum dot Chlorella polykrikoides composite material for radiotherapy sensitization according to claim 5, characterized in that, In the preparation of the aminated quantum dots in step (2), 5 mg of the tungsten-chromium-doped zinc gallate quantum dots are added to a solvent composed of 10 mL of N,N-dimethylformamide and 80 μL of 3-aminopropyl triethoxysilane, stirring is performed for 15 minutes to mix uniformly, and then magnetic heating stirring is performed on a magnetic heating stirrer in a 85 DEG C water bath for 12 hours; then the reacted solution is centrifuged at 10000 rpm for 10 minutes, and washing is performed with deionized water for 3 times, and the aminated quantum dots are obtained.

7. The method for preparing a modified quantum dot Chlorella polykrikoides composite material for radiotherapy sensitization according to claim 1 or 6, characterized in that, In the preparation of the modified quantum dots in step (3), the method used is: 20 mg of amino-modified quantum dots obtained in step (2) is mixed with a polysaccharide mixture composed of 20 mg of α-maltose, 10 mg of cellulose and 5 mg of sodium alginate, and each is dissolved in 20 mL of deionized water and stirred for 15 minutes, and then the two solutions are mixed uniformly; the resulting solution is heated and stirred on a magnetic stirrer in a 70°C water bath for 12 hours to obtain a milky white solution; then centrifuged at 10000 rpm for 10 minutes, washed with deionized water for 3 times, and finally dried for 6 hours to obtain the modified quantum dots.

8. The method for preparing a modified quantum dot Chlorella polykrikoides composite material for radiotherapy sensitization according to claim 1, characterized in that, In step (4), the method used for preparing the modified quantum dot Chlorella composite material is: 20 mg of modified quantum dots obtained in step (3) is mixed with 100 mL of Chlorella solution in the logarithmic phase with BG11 medium as the solvent, and placed in a shaker at 100 rpm / min, and incubated under a light intensity of 3000 lux for 1 hour; then centrifuged at 3000 rpm for 3 minutes to obtain a green precipitate, and then the precipitate is dissolved in PBS solution.

9. A modified quantum dot Chlorella polykrikoides composite for radiotherapy sensitization, characterized in that, The composite material is prepared by the preparation method of any one of claims 1-8.

10. Use of the composite material of claim 9 in the preparation of a radiotherapy sensitizer for treating tumors.

Images