Application of lanthanum-doped zinc oxide quantum dots as carriers in preparation of antitumor active substances

Abstract

The application belongs to the field of medical material application, and particularly relates to application of lanthanum-doped zinc oxide quantum dots as a carrier in preparation of an antitumor active substance. An ethanol solution of zinc acetate containing lanthanum and an ethanol solution of a strong base are mixed and reacted in an ice bath to obtain an ethanol solution of lanthanum-doped ZnO quantum dots, then n-hexane is added for extraction, centrifugal separation is performed, supernatant is removed, and vacuum drying is performed to obtain lanthanum-doped ZnO quantum dots; the lanthanum-doped ZnO quantum dots are modified by polyethylene glycol and hyaluronic acid to obtain a HA-PEG-La-ZnO composite nano drug carrier platform. The method is simple, low in cost, and beneficial to large-scale production; the lanthanum-doped ZnO quantum dots have high fluorescence intensity and fluorescence quantum yield, and can be used in the fields of biological imaging, drug carriers and the like.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of medical material applications, and particularly relates to application of lanthanum-doped zinc oxide quantum dots as carriers in preparation of antitumor active substances. BACKGROUND

[0002] Nanocomposites have comprehensive functions of imaging, targeting, drug delivery and cancer treatment, and show great application potential in anticancer medicine. In the past few decades, quantum dot clusters have attracted high interest in bioimaging and drug delivery. Quantum dots mainly play two roles in drug transport systems. First, quantum dots can be used as drug carriers and fluorescent probes to track the distribution of drugs in the body. Second, quantum dots can help elucidate drug metabolism kinetics and pharmacodynamics.

[0003] Zinc oxide quantum dots are a promising candidate material due to their low cost, easy preparation and pH-responsive degradation. However, the use of zinc oxide as a biomarker in the preparation of antitumor active substances is limited by insufficient fluorescence intensity. SUMMARY

[0004] The application aims to provide application of lanthanum-doped zinc oxide quantum dots as carriers in preparation of antitumor active substances. The application applies lanthanum-doped zinc oxide quantum dots as carriers in preparation of antitumor active substances, and significantly improves the fluorescence intensity of zinc oxide quantum dots.

[0005] To achieve the above application purposes, the application provides the following technical solutions.

[0006] The application provides application of lanthanum-doped zinc oxide quantum dots as carriers in preparation of antitumor active substances.

[0007] Preferably, the application comprises the following steps.

[0008] The lanthanum-doped zinc oxide quantum dots are mixed with 3-aminopropyl triethoxysilane for surface modification to obtain aminated lanthanum-doped zinc oxide quantum dots.

[0009] The aminated lanthanum-doped zinc oxide quantum dots are mixed with polyethylene glycol dicarboxylic acid for amidation reaction to obtain an amidation product.

[0010] The amidation product is mixed with hyaluronic acid for modification to obtain a modified amidation product.

[0011] The modified amidation product is mixed with an antitumor active substance for loading.

[0012] Preferably, the molar ratio of zinc to lanthanum in the lanthanum-doped zinc oxide quantum dots is 100:2-10.

[0013] Preferably, the lanthanum-doped zinc oxide quantum dots have a particle size of 2-10 nm.

[0014] Preferably, the lanthanum-doped zinc oxide quantum dots are prepared by a method comprising the following steps:

[0015] Zinc acetate, lanthanum salt and anhydrous ethanol are mixed to obtain a lanthanum-containing zinc acetate ethanol solution;

[0016] The lanthanum-containing zinc acetate ethanol solution is mixed with a strong base ethanol solution, and then subjected to ice bath reaction, extraction and drying in sequence to obtain the lanthanum-doped zinc oxide quantum dots; the strong base comprises one or more of lithium hydroxide, sodium hydroxide and potassium hydroxide.

[0017] Preferably, the mass ratio of the lanthanum-doped zinc oxide quantum dots to 3-aminopropyl triethoxysilane is 100:40-200.

[0018] Preferably, the surface modification is performed at a temperature of 110-130℃ for 10-20 min.

[0019] Preferably, the mass ratio of the lanthanum-doped zinc oxide quantum dots to polyethylene glycol dicarboxylic acid is 100:25-50.

[0020] Preferably, the mass to molar amount ratio of the amidation product to hyaluronic acid is 5 mg:0.012-0.02 mmol.

[0021] Preferably, the mass ratio of the antitumor active substance to the modified amidation product is 5:1-1.5.

[0022] The application provides a use of lanthanum-doped zinc oxide quantum dots as a carrier in preparation of an antitumor active substance.

[0023] The lanthanum-doped zinc oxide quantum dots provided by the application are used as a nano-drug loading platform, and the data of the examples show that the HA-PEG-La-ZnO@DOX nanoparticles obtained after loading doxorubicin have an antitumor effect 1.2-1.6 times that of pure ZnO@DOX. Meanwhile, the lanthanum-doped zinc oxide quantum dots of the application can load a high dose of antitumor active substances, can track the release kinetics of the drug in the body, and can achieve a better antitumor effect.

[0024] Further, the method for preparing the lanthanum-doped zinc oxide quantum dots is simple, low in cost and conducive to industrialized production. BRIEF DESCRIPTION OF DRAWINGS

[0025] In order to more clearly illustrate the technical solutions of the embodiments of the present application or the prior art, the drawings needed in the embodiments will be briefly introduced as follows. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without any creative effort on the basis of these drawings.

[0026] Figure 1 Preparation schematic diagram of lanthanum-doped zinc oxide quantum dots;

[0027] Figure 2 Transmission electron microscope image of the lanthanum-doped zinc oxide quantum dots obtained in Example 1;

[0028] Figure 3 Fluorescence intensity PL spectrum of the product obtained before loading DOX of Examples 1-5 and Comparative Example 1;

[0029] Figure 4 Anti-tumor effect diagram of different quantum dots after drug loading. DETAILED DESCRIPTION

[0030] The present application provides an application of lanthanum-doped zinc oxide quantum dots as a carrier in preparation of an anti-tumor active substance.

[0031] In the present application, the application preferably comprises the following steps:

[0032] The lanthanum-doped zinc oxide quantum dots are mixed with 3-aminopropyl triethoxysilane for surface modification to obtain aminated lanthanum-doped zinc oxide quantum dots.

[0033] The aminated lanthanum-doped zinc oxide quantum dots are mixed with polyethylene glycol dicarboxylic acid for amidation reaction to obtain an amidation product.

[0034] The amidation product is mixed with hyaluronic acid for modification to obtain a modified amidation product.

[0035] The modified amidation product is mixed with an anti-tumor active substance for loading.

[0036] In the present application, if not specifically stated, the raw materials used are commercially available products in the art.

[0037] The present application mixes lanthanum-doped zinc oxide quantum dots with 3-aminopropyl triethoxysilane for surface modification to obtain aminated lanthanum-doped zinc oxide quantum dots.

[0038] In the present application, the molar ratio of zinc to lanthanum in the lanthanum-doped zinc oxide quantum dots is preferably 100:2-10, and more preferably 100:4.

[0039] In the present application, the particle size of the lanthanum-doped zinc oxide quantum dots is preferably 2-10 nm.

[0040] In the present application, the lanthanum-doped zinc oxide quantum dots are preferably prepared by a method comprising the following steps:

[0041] Zinc acetate, lanthanum salt and anhydrous ethanol are mixed to obtain a lanthanum-containing zinc acetate ethanol solution;

[0042] After the lanthanum-containing zinc acetate ethanol solution is mixed with a strong base ethanol solution, ice bath reaction, extraction and drying are sequentially performed to obtain the lanthanum-doped zinc oxide quantum dots; the strong base comprises one or more of lithium hydroxide, sodium hydroxide and potassium hydroxide.

[0043] In the present application, zinc acetate, lanthanum salt and anhydrous ethanol are mixed to obtain a lanthanum-containing zinc acetate ethanol solution.

[0044] In the present application, the molar ratio of zinc acetate to lanthanum salt is preferably 100:2-10, and more preferably 100:4.

[0045] In the present application, the zinc acetate is preferably zinc acetate dihydrate.

[0046] In the present application, the zinc acetate is preferably dissolved in anhydrous ethanol before the lanthanum salt is added, and the dissolution is preferably performed by stirring.

[0047] In the present application, the lanthanum salt preferably comprises lanthanum acetate and / or lanthanum nitrate, and more preferably lanthanum acetate.

[0048] In the present application, the mixing temperature is preferably 70-90°C, and more preferably 80°C; the mixing time is preferably 1-3 h, and more preferably 2 h; and the mixing is preferably performed under reflux with stirring.

[0049] In the present application, after the mixing is completed, natural cooling to room temperature is preferably further performed to obtain the lanthanum-containing zinc acetate ethanol solution, which is a clear and transparent solution.

[0050] In the present application, the concentration of lanthanum ions in the lanthanum-containing zinc acetate ethanol solution is preferably 0.2-1 mmol / 100 mL, and the concentration of zinc acetate is preferably 10 mmol / 100 mL.

[0051] After obtaining the lanthanum-containing zinc acetate ethanol solution, the lanthanum-containing zinc acetate ethanol solution is mixed with a strong base ethanol solution, and ice bath reaction, extraction and drying are sequentially performed to obtain the lanthanum-doped zinc oxide quantum dots; the strong base comprises one or more of lithium hydroxide, sodium hydroxide and potassium hydroxide.

[0052] In the present application, the strong base is preferably lithium hydroxide.

[0053] In the present application, the mass ratio of zinc acetate to strong base is preferably 1-10:1, more preferably 1:1.

[0054] In the present application, the ethanol solution of strong base is preferably prepared by a method comprising the following steps: adding anhydrous ethanol to strong base and stirring under reflux at 85℃ water bath for 2-4h to obtain a clear and transparent solution.

[0055] In the present application, the mixing method of the lanthanum-containing zinc acetate ethanol solution and the ethanol solution of strong base is preferably dropwise adding the ethanol solution of strong base to the lanthanum-containing zinc acetate ethanol solution.

[0056] In the present application, the rate of dropwise adding is preferably 120 drops / min.

[0057] In the present application, the time of ice bath reaction is preferably 8-12h, more preferably 10h, and the temperature is preferably -5-5℃, more preferably 0℃.

[0058] In the present application, the ice bath reaction is preferably accompanied by stirring.

[0059] In the present application, the solvent of extraction preferably comprises n-hexane, and the time of extraction is preferably 12-18h, in a specific embodiment of the present application, such as overnight extraction.

[0060] In the present application, the extraction is preferably followed by solid-liquid separation to obtain a precipitate, and the method of solid-liquid separation is preferably centrifugation, the rotation speed of centrifugation is preferably 4500r / min, and the time is preferably 5min; the present application preferably dries the precipitate to obtain the lanthanum-doped zinc oxide quantum dots, and the drying temperature is preferably 60℃, and the time is preferably 36h.

[0061] The present application preferably mixes the lanthanum-doped zinc oxide quantum dots with an aqueous 3-aminopropyltriethoxysilane solution for surface modification, and the volume ratio of 3-aminopropyltriethoxysilane to water in the aqueous 3-aminopropyltriethoxysilane solution is preferably 0.4:2, and the water is preferably ultrapure water.

[0062] In the present application, the mass ratio of lanthanum-doped zinc oxide quantum dots to 3-aminopropyltriethoxysilane (APTES) is 100:40-200.

[0063] In the present application, the temperature of the surface modification is preferably 110-130℃, more preferably 120℃, and the time is preferably 10-20min, more preferably 15min. During the surface modification, APTES is mixed with ultrapure water in the preparation of the APTES aqueous solution, and the hydrolysis reaction occurs under stirring at 110-130℃, the ethoxysilane groups (Si-OC2H5) are hydrolyzed into silanol groups (Si-OH), and a primary polymerization layer is formed. The silanol groups and the Zn-OH on the surface of the ZnO quantum dots are converted into siloxane bonds through silanol-hydroxyl bridges and release water molecules, the silanol-silanol bridges are converted into siloxane bonds and release water molecules, and the remaining hydroxyl groups are converted into methyl groups, thereby preventing the further growth and agglomeration of the ZnO quantum dots.

[0064] Preferably, in the present application, the lanthanum-doped zinc oxide quantum dots are first dispersed in N,N-dimethylformamide (DMF), and then mixed with the 3-aminopropyltriethoxysilane for surface modification.

[0065] In the present application, the mass ratio of the lanthanum-doped zinc oxide quantum dots to DMF is preferably 100mg:15mL.

[0066] Preferably, after the surface modification, the present application further comprises centrifugation and washing in sequence to obtain the aminated lanthanum-doped zinc oxide quantum dots.

[0067] In the present application, the rotation speed of the centrifugation is preferably 1000rmp, and the time is preferably 5min.

[0068] In the present application, the solvent for the washing is preferably DMF.

[0069] Preferably, in the present application, the aminated lanthanum-doped zinc oxide quantum dots (NH2-La-ZnO quantum dots) are dispersed in water, and stored at 4℃ for standby use, and the mass ratio of the water to the lanthanum-doped zinc oxide quantum dots is preferably 10mL:100mg.

[0070] After obtaining the aminated lanthanum-doped zinc oxide quantum dots, the present application mixes the aminated lanthanum-doped zinc oxide quantum dots with polyethylene glycol dicarboxylic acid for an amidation reaction to obtain an amidation product (PEG-NH2-La-ZnO).

[0071] In the present application, the mass ratio of the lanthanum-doped zinc oxide quantum dots to polyethylene glycol dicarboxylic acid is 100:25-50, more preferably 1:1.

[0072] In the present application, the weight average molecular weight of the polyethylene glycol dicarboxylic acid (COOH-PEG-COOH) is preferably 2000.

[0073] In the present application, the polyethylene glycol dicarboxylic acid is preferably activated before use, and the activation preferably comprises the following steps: mixing 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide / N-hydroxysuccinimide (EDC / NHS) with an aqueous solution of polyethylene glycol dicarboxylic acid, adjusting the pH value, and then oscillating.

[0074] In the present application, the pH value is preferably 7, and the pH value adjusting agent is preferably sodium hydroxide.

[0075] In the present application, the mass ratio of EDC / NHS to polyethylene glycol dicarboxylic acid is preferably 50-200:25, and more preferably 50:25; and the molar ratio of EDC to NHS in the EDC / NHS is preferably 1:1.

[0076] In the present application, the oscillation temperature is preferably 25°C, and the oscillation time is preferably 30 min.

[0077] In the present application, the amidation reaction temperature is preferably room temperature, and the amidation reaction time is preferably 4-8 h. After the amidation reaction is completed, the unreacted COOH-PEG-COOH is preferably removed.

[0078] In the present application, the amidation product is preferably freeze-dried and stored.

[0079] After obtaining the amidation product, the amidation product is mixed with hyaluronic acid to modify the amidation product, thereby obtaining a modified amidation product (HA-PEG-NH2-La-ZnO).

[0080] In the present application, the mass of the amidation product to the molar amount of hyaluronic acid is preferably 5 mg:0.012-0.02 mmol, and more preferably 5 mg:0.016 mmol.

[0081] In the present application, the hyaluronic acid is preferably activated before use, and the activation preferably comprises the following steps: mixing the hyaluronic acid with water to obtain a hyaluronic acid aqueous solution, adjusting the pH value of the hyaluronic acid aqueous solution, and then mixing with EDC / NHS; and the molar ratio of EDC to NHS in the EDC / NHS is preferably 1:1.

[0082] In the present application, the concentration of the hyaluronic acid aqueous solution is preferably 0.004 mmol / mL.

[0083] In the present application, the pH value is preferably 4.

[0084] In the present application, the molar ratio of EDC / NHS to hyaluronic acid is preferably 320:0.016.

[0085] In the present application, the mixing time is preferably 4-8h.

[0086] In the present application, the modification time is preferably 12-18h, preferably under stirring. In a specific embodiment of the present application, the stirring is overnight.

[0087] After the modification is completed, dialysis is preferably further included to obtain the modified amidation product (HA-PEG-NH2-La-ZnO). In the present application, the molecular weight cut-off of the dialysis is preferably 3500Da, and the purpose of the dialysis is to remove excess HA.

[0088] After the modified amidation product is obtained, the present application mixes the modified amidation product with an antitumor active substance for loading.

[0089] In the present application, the mass ratio of the antitumor active substance to the modified amidation product is preferably 5:1-1.5.

[0090] In the present application, the antitumor active substance is preferably doxorubicin (DOX), and the concentration of the doxorubicin is preferably 1mg / mL. The doxorubicin is preferably dissolved in ultrapure water.

[0091] In the present application, the loading process preferably further includes adding EDC and NHS, and the molar ratio of the EDC to the NHS is preferably 2:1.

[0092] In the present application, the loading time is preferably 12-18h, preferably under stirring. In a specific embodiment of the present application, the stirring is overnight.

[0093] In order to further illustrate the present application, the application of lanthanum-doped zinc oxide quantum dots as carriers in the preparation of antitumor active substances is described in detail below in conjunction with the accompanying drawings and examples, but they should not be understood as limiting the scope of protection of the present application.

[0094] Example 1

[0095] 2.20g of zinc acetate dihydrate was added to 100mL of anhydrous ethanol, and stirred with a magnetic stirrer until dissolved. Then, 0.2mmol of lanthanum acetate was added to the zinc acetate ethanol solution, and stirred under reflux at 80℃ water bath for 2h until the solution became clear and transparent, obtaining a lanthanum-containing zinc acetate ethanol solution.

[0096] According to the mass ratio of zinc acetate and lithium hydroxide is 1:1, LiOH was weighed and dissolved in 150 mL of anhydrous ethanol, and stirred at 85°C water bath for 2h until the solution was clear and transparent. After cooling to room temperature, the LiOH ethanol solution was added dropwise into the lanthanum-containing zinc acetate ethanol solution, and stirred in an ice bath for 8 hours. The obtained solution was extracted with n-hexane overnight, and the precipitate was centrifuged at 4500 r / min for 5 min and dried at 60°C to obtain lanthanum-doped zinc oxide quantum dot powder with a particle size of 2-8 nm.

[0097] Surface modification of quantum dots: 100 mg of lanthanum-doped ZnO quantum dot powder was ultrasonically dispersed in 15 mL of DMF solution. After heating to 120°C, 50 μL of 3-aminopropyltriethoxysilane aqueous solution (APTES) was added and stirred for 15 min, centrifuged at 1000 rpm for 5 min, washed with DMF and collected the amino-functionalized ZnO quantum dots (NH2-La-ZnO quantum dots) were dispersed in 10 mL of water and stored at 4°C.

[0098] Modification of COOH-PEG-COOH (Mw: 2000) to the surface of NH2-La-ZnO quantum dots by amidation reaction: First, 0.2 g of EDC / NHS was added to 1 mL of ultrapure water containing 25 mg of polyethylene glycol dicarboxylic acid. Then the pH value of the mixture was adjusted to 7 with NaOH, and the COOH-PEG-COOH was activated at 25°C for 30 min. After activation, 2.5 mL of NH2-La-ZnO dispersion was added and stirred at room temperature for 4 h. After removing the unmodified COOH-PEG-COOH, the final product was freeze-dried and stored (PEG-La-ZnO).

[0099] HA modification of PEG-La-ZnO: First, 0.016 mmol of HA was dissolved in 4 mL of ultrapure water, and then the pH value was adjusted to 4 with hydrochloric acid and incubated at room temperature overnight. Then, 0.32 mol of EDC / NHS (molar ratio of EDC to NHS is 1:1) was added to the prepared HA solution and activated for 4 h. Finally, 5 mg of PEG-La-ZnO quantum dots was added to the above solution and stirred overnight. The obtained HA-PEG-La-ZnO nanoparticles were dialyzed in a water dialysis bag for 24 hours to remove excess HA.

[0100] Loading of DOX: First, a 1 mg / mL solution of DOX was prepared. Then, 0.32 mmol of EDC and 0.16 mmol of NHS were mixed with the HA-PEG-ZnO solution and stirred for 30 min, followed by the addition of the prepared DOX solution (mass ratio of HA-PEG-La-ZnO nanoparticles to DOX is 5:1), and stirred in the dark overnight.

[0101] The product obtained in the embodiment is HA-PEG-2La-ZnO@DOX nanoparticles, wherein the preparation schematic diagram of the lanthanum-doped zinc oxide quantum dots is shown in Figure 1 .

[0102] Example 2

[0103] The embodiment is different from the above-mentioned embodiment 1 only in that the amount of substance of lanthanum acetate is different, and the amount of substance of lanthanum acetate in the embodiment is 0.4 mmol. The product obtained is HA-PEG-4La-ZnO@DOX nanoparticles.

[0104] Example 3

[0105] The embodiment is different from the above-mentioned embodiment 1 only in that the amount of substance of lanthanum acetate is different, and the amount of substance of lanthanum acetate in the embodiment is 0.6 mmol. The product obtained is HA-PEG-6La-ZnO@DOX nanoparticles.

[0106] Example 4

[0107] The embodiment is different from the above-mentioned embodiment 1 only in that the amount of substance of lanthanum acetate is different, and the amount of substance of lanthanum acetate in the embodiment is 0.8 mmol. The product obtained is HA-PEG-8La-ZnO@DOX nanoparticles.

[0108] Example 5

[0109] The embodiment is different from the above-mentioned embodiment 1 only in that the amount of substance of lanthanum acetate is different, and the amount of substance of lanthanum acetate in the embodiment is 1 mmol. The product obtained is HA-PEG-10La-ZnO@DOX nanoparticles.

[0110] Comparative Example 1

[0111] The comparative example is different from the above-mentioned embodiment 1 only in that no lanthanum acetate is added. The product obtained is HA-PEG-ZnO@DOX.

[0112] Test Example 1

[0113] The transmission electron microscope image of the lanthanum-doped zinc oxide quantum dots obtained in the embodiment 1 is shown in Figure 2 . Figure 2 It can be seen that the particle size of the lanthanum-doped zinc oxide quantum dots of the present application is less than 10 nm.

[0114] The product obtained in the embodiment 1-5 (labeled as 2La-ZnO, 4La-ZnO, 6La-ZnO, 8La-ZnO and 10La-ZnO in the figure respectively) and the comparative example 1 (labeled as ZnO in the figure) before loading DOX, the ethanol solution fluorescence emission peak position is 525 nm, and the fluorescence spectrum and fluorescence emission intensity are shown in Figure 3 .

[0115] The comparative data can show that the fluorescence intensity of HA-PEG-4La-ZnO in Example 2 is 8 times higher than that of HA-PEG-ZnO in Comparative Example 1; and the fluorescence intensity of HA-PEG-10La-ZnO in Example 5 is similar to that of HA-PEG-ZnO in Comparative Example 1.

[0116] Application Example 1

[0117] Method: In order to carry out the toxicity study, B16 cells were inoculated on 96-well plates, and the cell density was 1×10 4 cells / cm 2 , incubated for 48 hours, and then the pure ZnO and La-ZnO products before loading DOX were incubated with the cells for 24 hours to investigate the biocompatibility of ZnO and La-ZnO. At the same time, the cells were incubated with free DOX, HA-PEG-ZnO@DOX of Comparative Example 1 (labeled as ZnO@DOX in the figure) and HA-PEG-4La-ZnO@DOX of Example 2 (labeled as 4La-ZnO@DOX in the figure) for 24 hours. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution was added, incubated for 4h, then MTT was removed and the cells were dissolved in DMSO solution, and the absorbance was measured at 492nm by an enzyme marker, and the test results are shown in Figure 4

[0118] It can be seen from the test results that the toxicity of pure DOX is relatively small, and the cell inhibition effect of ZnO-DOX and 4La-ZnO-DOX groups is good. When the concentration of DOX is 2.43μg / mL, the cell viability of each group is reduced to 70%, and with the increase of the concentration, the cell toxicity of each group is significantly reduced, and when the concentration increases to 4.05μg / mL, the cell viability of free DOX, ZnO@DOX and La-ZnO@DOX is reduced to 18%, 15% and 12% respectively. The anti-tumor effect of HA-PEG-4La-ZnO in Example 2 is 1.25 times higher than that of HA-PEG-ZnO in Comparative Example 1.

[0119] The lanthanum-doped zinc oxide quantum dots exhibit good anti-tumor effect, which indicates that the synthesized La-doped ZnO quantum dots not only have good fluorescence imaging capability, but also have good anti-tumor effect.

[0120] Although the above examples have made a detailed description of the present application, it is only a part of the examples of the present application, but not all the examples, and other examples can be obtained under the non-creative premise according to the examples of the present application, which all belong to the protection scope of the present application.​

Claims

1. The application of lanthanum-doped zinc oxide quantum dots as a carrier in the preparation of antitumor active substances, the application comprising the following steps: Lanthanum-doped zinc oxide quantum dots were mixed with 3-aminopropyltriethoxysilane for surface modification to obtain aminated lanthanum-doped zinc oxide quantum dots; the molar ratio of zinc to lanthanum in the lanthanum-doped zinc oxide quantum dots was 100:4; the mass ratio of lanthanum-doped zinc oxide quantum dots to 3-aminopropyltriethoxysilane was 100:40~200. The aminated lanthanum-doped zinc oxide quantum dots were mixed with polyethylene glycol dicarboxylic acid and subjected to an amidation reaction to obtain an amidated product; the mass ratio of the lanthanum-doped zinc oxide quantum dots to polyethylene glycol dicarboxylic acid was 100:25~50. The amidation product was mixed with hyaluronic acid for modification to obtain a modified amidation product; the mass ratio of the amidation product to the molar amount of hyaluronic acid was 5 mg: 0.012~0.02 mmol. The modified amidation product is mixed with an antitumor active substance and loaded; the mass ratio of the antitumor active substance to the modified amidation product is 5:1 to 1.

5. The method for preparing the lanthanum-doped zinc oxide quantum dots is as follows: Zinc acetate, lanthanate, and anhydrous ethanol are mixed to obtain a lanthanum-containing zinc acetate ethanol solution. The lanthanum-containing zinc acetate ethanol solution was mixed with a strong base ethanol solution and then subjected to ice bath reaction, extraction and drying in sequence to obtain the lanthanum-doped zinc oxide quantum dots; the strong base includes one or more of lithium hydroxide, sodium hydroxide and potassium hydroxide.

2. The application according to claim 1, characterized in that, The lanthanum-doped zinc oxide quantum dots have a particle size of 2~10 nm.

3. The application according to claim 1, characterized in that, The surface modification temperature is 110~130℃, and the time is 10~20min.

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