Intelligent copper release nano preparation triggered by magnetic effect as well as preparation method and drug application of intelligent copper release nano preparation

Abstract

The invention provides an intelligent copper release nano preparation triggered by a magnetic effect as well as a preparation method and drug application thereof. The preparation is ES (at) Fe3O4 (at) SiO2-Cu; the preparation method comprises the following steps: adding FeCl3. 6h2O and CH3COONa into ethylene glycol, and carrying out hydrothermal reaction, washing and magnetic separation; dispersing the ferric oxide magnetic fluid in ammonia water for ultrasonic treatment, adding an ethanol solution containing 20% of tetraethyl silicate and a copper nitrate mixed solution for continuous reaction, washing with ethanol water, performing magnetic separation, dispersing the Fe3O4-coated SiO2-Cu fluid in an ammonium nitrate isopropanol solution, adding isopropanol water for ultrasonic treatment after magnetic separation, washing with ethanol water, replacing water with pure ethanol, and performing vacuum drying to obtain Fe3O4-coated SiO2-Cu; dispersing the mixture and ES in water, and carrying out violent ultrasonic oscillation; and dialyzing the bag overnight, and collecting to obtain ES (at) Fe3O4 (at) SiO2-Cu. The device is high in penetration depth, suitable for deep tumor treatment and good in heating efficiency under an alternating magnetic field.

Description

Technical Field

[0001] The present invention relates to the technical field of nano-drug delivery, and in particular, to a magneto-effect-triggered intelligent copper-releasing nanoformulation, a preparation method thereof, and a pharmaceutical application thereof. Background Art

[0002] Cuproptosis is a recently discovered copper-dependent immunogenic cell death mode, and inducing cuproptosis is a promising anti-tumor treatment strategy. However, this treatment strategy for copper-induced tumor cell death faces two major difficulties to be solved: low copper ion concentration in tumor cells and short blood half-life of copper ion carrier drugs.

[0003] Therefore, constructing a copper-induced nano-drug delivery system (Nano drug delivery system, NDDS) is the key for the cuproptosis-based tumor treatment strategy to enter clinical applications.

[0004] Examples of the current laboratory preparation steps of copper nanoparticles are as follows:

[0005] (1) Mix 5 mL of 0.5 mM HAuCl 4 with 5 mL of 0.2 mM CTAB solution. Inject 0.6 mL of fresh 0.01 M sodium borohydride under vigorous stirring. After the color of the solution changes from yellow to brownish yellow, continue stirring for 2 min. Age the solution at room temperature for 30 min to obtain a seed solution. Dissolve 1.8 g of CTAB and 0.22 g of 5-BrSA in 50 mL of warm water to prepare a growth solution. After cooling the solution to 30 °C, add 2.4 mL of 4 mM silver nitrate solution and stir gently. Keep the mixture at 30 °C for 15 min, then add 50 mL of 1 mM HAuCl4 solution. After slow stirring for 15 min, add 0.4 mL of 0.064 M ascorbic acid and stir vigorously for 30 s until colorless. Finally, inject 0.16 mL of the seed solution into the growth solution. Stir the mixture for 30 s and store it at 30 °C for 12 h.

[0006] (2) Prepare a 20% TEOS ethanol solution containing Cu(NO 3 ) 2 with Si / Cu being 30:1. Add the synthesized Au NRs to 30 mL of ammonium hydroxide (0.51 M) and stir at 40 °C, then add 90 μL of the Si / Cu ethanol solution into the solution three times. After gentle stirring for 2 days, collect the nanoparticles by centrifugation (8000 rpm, 15 min).

[0007] (3) Disperse 10 mg of Au@MSN-Cu in 10 mL of ethanol solution containing 2 mg / mL of mpeg-silane, and gently stir at 60 °C for 24 h. After cooling to room temperature, centrifuge to collect Au@MSN-Cu / PEG, and wash it three times with ethanol.

[0008] (4) Disperse 10 mg of Au@MSN-Cu / PEG in 2 mL of ethanol solution containing 40 mg of DSF (disulfiram), ultrasonically vibrate for 1 hour, and vigorously stir the mixture overnight (stirring overnight is 16 hours).

[0009] However, the above-mentioned copper nanoparticles prepared by the prior art and the corresponding drug delivery methods have the following disadvantages:

[0010] 1. The cost of gold (Au) nanoparticles is high, which is not suitable for industrial production and clinical transformation.

[0011] 2. Using near-infrared light irradiation to generate heat drive is not applicable to deep tumors. Infrared irradiation is difficult to penetrate the fat layer and can only penetrate 4-5 cm under the skin, which is suitable for superficial tissue tumors and its use is limited; and the intensity and irradiation time of the irradiation site of infrared near-light need to be strictly controlled, otherwise it is easy to cause harm to the skin.

[0012] 3. The existing heat fields based on radio frequency, ultrasound, etc. as heat drives are highly focused at one point, and the heat needs to be conducted from the tissue to the drug delivery system. The heat conduction process will cause overheated areas, suitable temperature areas and cold areas, and it is difficult for the drug delivery system to release drugs evenly. Summary of the Invention

[0013] In view of this, the first object of the present invention is to provide a magneto-effect-triggered intelligent copper-releasing nanoformulation with iron oxide Fe 3 O 4 as the core, which can be triggered by the magneto-effect, has strong penetration depth, is suitable for deep tumor treatment, induces uniform, rapid and controllable heat production, and reduces costs, and is suitable for industrial production and clinical transformation.

[0014] The second object of the present invention is to provide a preparation method of the above-mentioned magneto-effect-triggered intelligent copper-releasing nanoformulation, and the preparation method has a simple production process and is convenient for on-site application.

[0015] The third object of the present invention is to provide the application of the above-mentioned magneto-effect-triggered intelligent copper-releasing nanoformulation in the preparation of drugs for treating tumors. Through the drug delivery triggered by the magneto-effect, it effectively promotes the uptake of nano-drugs by tumor cells.

[0016] In order to achieve the above objects of the present invention, the following technical solutions are specifically adopted:

[0017] The present invention provides a magneto-effect-triggered intelligent copper-releasing nanoagent, and the intelligent copper-releasing nanoagent is copper compound ES@Fe 3 O 4 @SiO 2 -Cu. That is, the copper compound ES@Fe 3 O 4 @SiO 2 -Cu has iron oxide Fe 3 O 4 as the core.

[0018] The present invention also provides a preparation method of the magneto-effect-triggered intelligent copper-releasing nanoagent for preparing the magneto-effect-triggered intelligent copper-releasing nanoagent as described above, including the following steps:

[0019] S1. Add equal mass parts of FeCl 3 ·6h 2 O and CH 3 COONa into ethylene glycol, add them into a hydrothermal reaction kettle, and react at 195 - 205 °C for 11 - 13 hours. Wash and magnetically separate to obtain iron oxide magnetic fluid Fe 3 O 4 ;

[0020] S2. Disperse the iron oxide magnetic fluid Fe 3 O 4 in ammonia water, ultrasonically vibrate and stir, add a mixed solution of tetraethyl orthosilicate-containing ethanol solution with 20% and copper nitrate with a molar concentration ratio of Si 4+ : Cu 2+ of 20:1, and continue to react for 47 - 49 h; add ethanol-water with a volume ratio of 1:1 for washing, and magnetically separate to obtain Fe 3 O 4 @SiO 2 -Cu fluid;

[0021] S3. Disperse the Fe 3 O 4 @SiO 2 -Cu fluid in an isopropyl alcohol solution of ammonium nitrate, and stir; after magnetic separation, add isopropyl alcohol-water with a volume ratio of 1:1, ultrasonically vibrate for 25 - 35 minutes, then add ethanol-water with a volume ratio of 1:1 for washing, and finally replace water with pure ethanol and vacuum dry to obtain Fe 3 O 4 @SiO 2 -Cu;

[0022] S4. Disperse the Fe 3 O 4 @SiO 2-Cu and the carrier drug ilixadencel ES were dispersed in anaerobic distilled water and ultrasonically shaken vigorously; dialyzed overnight using a dialysis bag, and the final product ES@Fe 3 O 4 @SiO 2 -Cu nanopreparation was obtained.

[0023] Preferably, the stirring temperature of the iron oxide magnetic fluid Fe 3 O 4 dispersed in ammonia water during stirring was 39 - 41 °C.

[0024] Preferably, the stirring speed of the iron oxide magnetic fluid Fe 3 O 4 dispersed in ammonia water during stirring was 95 - 105 rpm / min.

[0025] Preferably, the adding method of the ethanol solution containing 20% tetraethyl orthosilicate and the copper nitrate mixture in step S2 was: add one-third of the ethanol solution containing 20% tetraethyl orthosilicate and the copper nitrate mixture every 30 minutes, for a total of 3 times.

[0026] Preferably, the stirring time of the Fe 3 O 4 @SiO 2 -Cu fluid dispersed in the isopropyl alcohol solution of ammonium nitrate during stirring was 7 - 9 h.

[0027] Preferably, the ultrasonic time of the Fe 3 O 4 @SiO 2 -Cu and the carrier drug ilixadencel ES dispersed in anaerobic distilled water and ultrasonically shaken vigorously was 18 - 22 min.

[0028] The present invention also provides the application of the magneto-effect-triggered intelligent copper-releasing nanopreparation as described above in the preparation of a drug for treating tumors.

[0029] The intelligent copper-releasing nanopreparation prepared by the present invention is triggered by a magneto-effect, with a uniform magnetic field distribution, uniform, rapid, and controllable heat generation induced. By controlling the magnetic field intensity, the inner core iron oxide Fe 3 O 4 can be rapidly heated to 50 °C within 10 minutes and maintained at 50 °C ± 0.2 °C for 60 minutes.

[0030] Compared with the prior art, the beneficial effects of the present invention are:

[0031] The intelligent copper-releasing nanoformulation triggered by magnetic effect provided by the present invention, compared with the existing copper nanoparticles driven by near-infrared photothermal effect, has the advantages of strong penetration depth, small side effects of the magnetic field, being suitable for the treatment of deep tumors, overcoming the limitations of the existing technologies based on radio frequency, ultrasound, etc. as heat drivers, and having the advantages of uniform, rapid, and controllable heat generation induction. It is an ideal heat driving scheme for temperature-sensitive intelligent drug delivery systems. Through the self-induced heating of the inner core iron oxide Fe 3 O 4 under an alternating magnetic field, copper ions and elesclomol drugs are released, with a wider range of indications and higher safety; not limited by the size, location, and irregular shape of tumors, the magnetic field can penetrate the human body uniformly and has no obvious side effects, allowing the inner core of the drug delivery system to directly generate heat, resulting in the disintegration of the silica shell, and minimizing the damage to adjacent tissues; the inner core iron oxide Fe 3 O 4 nanoparticles are simpler to prepare and more cost-effective than gold nanoparticles, and have a better heating efficiency under an alternating magnetic field compared with infrared light irradiation, and the heating rate to 50 °C is increased by 17.6%. Detailed implementation manners

[0032] The implementation manners of the present invention will be described in detail below in conjunction with the embodiments. However, those skilled in the art will understand that the following embodiments are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. For those not specified in the embodiments, the conventional conditions or the conditions recommended by the manufacturer are followed. For the reagents or instruments not specified for the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0033] Example 1

[0034] Prepare anaerobic distilled water;

[0035] Add 2.4 g of FeCl 3 ·6h 2 O and 2.4 g of CH 3 COONa into a hydrothermal reaction kettle, react at 200 °C for 12 hours, wash and magnetically separate to obtain iron oxide magnetic fluid Fe 3 O 4 ;

[0036] Prepare a mixed solution of tetraethyl orthosilicate-containing ethanol solution with a concentration of 20% and copper nitrate, and the molar concentration ratio of Si 4+ : Cu 2+ is 20:1;

[0037] Add the iron oxide magnetic fluid Fe 3 O 4Dispersed in ammonia water, ultrasonic oscillation was carried out, and stirring was carried out at 40 °C with a stirring speed of 100 rpm / min. 2 mL of the ethanol solution containing 20% tetraethyl orthosilicate and the copper nitrate mixture was added every 30 minutes, for a total of 3 times, and the reaction was continued for 48 h; washing was carried out 3 times with ethanol-water with a volume ratio of 1:1, and magnetic separation was carried out to obtain Fe 3 O 4 @SiO 2 -Cu fluid;

[0038] The Fe 3 O 4 @SiO 2 -Cu fluid was dispersed in 60 mL of isopropyl alcohol ammonium nitrate solution, and stirring was carried out at 35 °C for 7 h; after magnetic separation, isopropyl alcohol-water with a volume ratio of 1:1 was added, ultrasonic oscillation was carried out for 30 minutes, and then washing was carried out multiple times with ethanol-water with a volume ratio of 1:1. Finally, 20 mL of pure ethanol was used to displace the water, and vacuum drying was carried out to obtain Fe 3 O 4 @SiO 2 -Cu;

[0039] 100 mg of the Fe 3 O 4 @SiO 2 -Cu and 4 mg of the carrier drug ilisimore ES were dispersed in anaerobic distilled water, and ultrasonic intense oscillation was carried out for 20 min; dialysis was carried out overnight with a dialysis bag, and the final product ES@Fe 3 O 4 @SiO 2 -Cu nanon preparation was collected.

[0040] Example 2

[0041] Prepare anaerobic distilled water;

[0042] 2.4 g of FeCl 3 ·6h 2 O and 2.4 g of CH 3 COONa were put into a hydrothermal reaction kettle and reacted at 205 °C for 11 hours, washed and magnetically separated to obtain iron oxide magnetic fluid Fe 3 O 4 ;

[0043] Prepare an ethanol solution containing 20% tetraethyl orthosilicate and a copper nitrate mixture, and the molar concentration of Si 4+ :Cu 2+ is 20:1;

[0044] The iron oxide magnetic fluid Fe 3 O 4Dispersed in ammonia water, ultrasonic oscillation was carried out, and stirring was carried out at 39 °C with a stirring speed of 95 rpm / min. 2 mL of the ethanol solution containing 20% tetraethyl orthosilicate and the copper nitrate mixture was added every 30 minutes, for a total of 3 times, and the reaction was continued for 47 h; washed 3 times with ethanol-water with a volume ratio of 1:1, and Fe was obtained by magnetic separation 3 O 4 @SiO 2 -Cu fluid;

[0045] The Fe 3 O 4 @SiO 2 -Cu fluid was dispersed in 60 mL of ammonium nitrate isopropanol solution, and stirred at 35 °C for 8 h; after magnetic separation, isopropanol-water with a volume ratio of 1:1 was added, ultrasonicated for 30 minutes, then washed multiple times with ethanol-water with a volume ratio of 1:1, and finally 20 mL of pure ethanol was used to displace the water, and vacuum dried to obtain Fe 3 O 4 @SiO 2 -Cu;

[0046] 100 mg of the Fe 3 O 4 @SiO 2 -Cu and 4 mg of the carrier drug ilisimore ES were dispersed in anaerobic distilled water, and ultrasonically shaken vigorously for 18 min; dialyzed overnight with a dialysis bag, and the final product ES@Fe 3 O 4 @SiO 2 -Cu nanon preparation.

[0047] Example 3

[0048] Prepare anaerobic distilled water;

[0049] 2.4 g of FeCl 3 ·6h 2 O, 2.4 g of CH 3 COONa were put into a hydrothermal reaction kettle and reacted at 205 °C for 13 hours, washed and magnetically separated to obtain iron oxide magnetic fluid Fe 3 O 4 ;

[0050] Prepare a mixed solution of ethanol solution containing 20% tetraethyl orthosilicate and copper nitrate, and the molar concentration of Si 4+ :Cu 2+ is 20:1;

[0051] The iron oxide magnetic fluid Fe 3 O 4Dispersed in ammonia water, ultrasonic oscillation was carried out, and stirring was carried out at 41 °C with a stirring speed of 100 rpm / min. 2 mL of the ethanol solution containing 20% tetraethyl orthosilicate and copper nitrate mixture was added every 30 minutes for a total of 3 times, and the reaction continued for 49 h; washing was carried out 3 times with ethanol-water with a volume ratio of 1:1, and magnetic separation was carried out to obtain Fe 3 O 4 @SiO 2 -Cu fluid;

[0052] Disperse the Fe 3 O 4 @SiO 2 -Cu fluid in 60 mL of ammonium nitrate isopropanol solution, and stir at 35 °C for 9 h; after magnetic separation, add isopropanol-water with a volume ratio of 1:1, ultrasonic for 35 minutes, then add ethanol-water with a volume ratio of 1:1 and wash multiple times. Finally, replace the water with 20 mL of pure ethanol and dry in vacuum to obtain Fe 3 O 4 @SiO 2 -Cu;

[0053] Disperse 100 mg of the said Fe 3 O 4 @SiO 2 -Cu and 4 mg of the carrier drug ilisomide ES in anaerobic distilled water, and carry out violent ultrasonic oscillation for 22 min; dialyze overnight and collect to obtain the final product ES@Fe 3 O 4 @SiO 2 -Cu nanoplatform.

[0054] Example 4

[0055] Other conditions are the same as those in Example 1. The difference from Example 1 is the use of 2.0 g of FeCl 3 ·6h 2 O, 2.0 g of CH 3 COONa.

[0056] Example 5

[0057] Other conditions are the same as those in Example 1. The difference from Example 1 is the use of 2.8 g of FeCl 3 ·6h 2 O, 2.8 g of CH 3 COONa.

[0058] Comparative Example 1

[0059] Different from Example 1, change the d molar concentration Si of the ethanol solution containing 20% tetraethyl orthosilicate and copper nitrate mixture 4+ :Cu 2+ to 19:1.

[0060] Comparative Example 2

[0061] Different from Example 1, different mass parts of FeCl 3 ·6h 2 O, CH 3 COONa were taken, which were 2.2 g of FeCl 3 ·6h 2 O, 2.6 g of CH 3 COONa respectively.

[0062] Comparative Example 3

[0063] Different from Example 1, the stirring speed of the iron oxide magnetic fluid Fe 3 O 4 dispersed and stirred in ammonia water was changed to 90 rpm / min.

[0064] Comparative Example 4

[0065] Different from Example 1, half of the ethanol solution containing 20% tetraethyl orthosilicate and the copper nitrate mixture were added every 30 minutes, for a total of 2 times.

[0066] Test Results

[0067] The copper nano - preparations prepared in the above examples and comparative examples were tested for the drug - delivery heating rate. The test data are shown in Table 1 below:

[0068] Table 1

[0069]

[0070] It can be seen from the data in Table 1 that through a reasonable preparation process, the drug - delivery heating rates of the magneto - effect - triggered intelligent copper - releasing nano - preparations of the present invention are all better than those of Comparative Examples 1 - 4. And the process parameters adopted in Example 1 of the present invention produce the most excellent effects.

[0071] For the comparison result between Comparative Example 1 and Example 1, when the molar concentration ratio of the ethanol solution containing 20% tetraethyl orthosilicate to copper nitrate mixture d Si 4+ : Cu 2+ was changed to 19:1, the coating effect of the SiO 2 -Cu complex was weakened, which had a certain impact on the chemical stability of the iron oxide core, so the drug - delivery heating efficiency was reduced.

[0072] For the comparison result between Comparative Example 2 and Example 1, when FeCl 3 ·6h 2 O, CH 3When different masses of COONa are taken, the product of the inner core iron oxide decreases, affecting the magnetic effect, and thus reducing the drug delivery heating efficiency.

[0073] For the comparison results of Comparative Example 3 and Example 1, when the stirring speed of the iron oxide magnetic fluid Fe 3 O 4 dispersed in ammonia water and stirred is changed to 90 rpm / min, the effect of the dispersion decreases, affecting the subsequent magnetic separation effect, and thus reducing the drug delivery heating efficiency.

[0074] For the comparison results of Comparative Example 4 and Example 1, when half of the ethanol solution containing 20% tetraethyl orthosilicate and the copper nitrate mixture are added every 30 minutes, the number of additions decreases, reducing the reaction efficiency between components, affecting the subsequent magnetic separation effect, and thus reducing the drug delivery heating efficiency.

[0075] Comparing Example 1 in Table 1 with Example 2 and Example 3, it can be seen that the drug delivery heating efficiency is the best when using the intermediate values within the process parameters such as reaction temperature, stirring speed, and reaction time.

[0076] In summary, the magnetically triggered intelligent copper-releasing nanoplatform prepared in the embodiments of the present invention has a strong penetration depth of the magnetic field, small side effects, is suitable for deep tumor treatment, and has advantages such as uniform, rapid, and controllable heat generation. It is an ideal thermal drive scheme for a temperature-sensitive intelligent drug delivery system. Through the self-induced heating of the inner core iron oxide Fe 3 O 4 under an alternating magnetic field, copper ions and elesclomol drugs are released, with a wider range of indications and higher safety; it is not limited by the size, location, and irregular shape of tumors, the magnetic field can penetrate the human body evenly without obvious side effects, allowing the inner core of the drug delivery system to directly generate heat, resulting in the disintegration of the silica shell, minimizing damage to adjacent tissues; the inner core iron oxide Fe 3 O 4 nanoparticles are easier to prepare and more cost-effective than gold nanoparticles, and have a better heating efficiency than infrared light irradiation under an alternating magnetic field. The heating rate to 50 °C is increased by 17.6%, effectively solving the problems restricted by existing technologies using radio frequency, ultrasound, etc. as thermal drives.

[0077] Although the invention has been illustrated and described with reference to specific embodiments, it should be realized that many other changes and modifications can be made without departing from the spirit and scope of the invention. Therefore, this means that all such changes and modifications that fall within the scope of the invention are included in the appended claims.

Claims

1. Intelligent copper-releasing nanoformulation triggered by magnetic effect, characterized in that: The intelligent copper-releasing nano-preparation is a copper compound ES@Fe3O4@SiO2-Cu.

2. A method for preparing a magnetic effect triggered smart copper-releasing nanoformulation, which is used to prepare the magnetic effect triggered smart copper-releasing nanoformulation as claimed in claim 1, characterized in that: The steps include: S1. Add equal parts of FeCl3·6h2O and CH3COONa to ethylene glycol, add the mixture to a hydrothermal reactor, react at 195-205°C for 11-13 hours, wash and magnetically separate to obtain iron oxide magnetic fluid Fe3O4; S2, dispersing the iron oxide magnetic fluid Fe3O4 in ammonia water, ultrasonically shaking, stirring, adding molar concentration Si 4+ :Cu 2+ The mixture is a 20:1 mixture of ethanol solution containing 20% ​​tetraethyl silicate and copper nitrate, and the reaction is continued for 47-49 hours; ethanol water with a volume ratio of 1:1 is added for washing, and Fe3O4@SiO2-Cu fluid is obtained by magnetic separation; S3, dispersing the Fe3O4@SiO2-Cu fluid in an ammonium nitrate isopropanol solution and stirring; after magnetic separation, adding isopropanol water in a volume ratio of 1:1, ultrasonically vibrating for 25-35 minutes, adding ethanol water in a volume ratio of 1:1 for washing, and finally replacing the water with pure ethanol, vacuum drying, to obtain Fe3O4@SiO2-Cu; S4. Disperse the Fe3O4@SiO2-Cu and the carrier drug ilisimol ES in oxygen-free distilled water, and vibrate violently with ultrasound; dialyze the bag overnight, and collect the final product ES@Fe3O4@SiO2-Cu nanoformulation.

3. The method for preparing the magnetic effect triggered intelligent copper-releasing nanoformulation according to claim 2, characterized in that: The stirring temperature of the iron oxide magnetic fluid Fe3O4 dispersed in the ammonia water in step S2 is 39-41°C.

4. The method for preparing the magnetic effect triggered intelligent copper-releasing nanoformulation according to claim 2, characterized in that: The stirring speed of the iron oxide magnetic fluid Fe3O4 dispersed in the ammonia water in step S2 is 95-105 rpm / min.

5. The method for preparing the magnetic effect triggered intelligent copper-releasing nanoformulation according to claim 2, characterized in that: The method for adding the ethanol solution containing 20% ​​tetraethyl silicate and the copper nitrate mixed solution in step S2 is: adding one third of the ethanol solution containing 20% ​​tetraethyl silicate and the copper nitrate mixed solution every 30 minutes, for a total of 3 times.

6. The method for preparing the magnetic effect triggered intelligent copper-releasing nanoformulation according to claim 2, characterized in that: The stirring time of the Fe3O4@SiO2-Cu fluid dispersed in the ammonium nitrate isopropanol solution in step S3 is 7-9 hours.

7. The method for preparing the magnetic effect triggered intelligent copper-releasing nanoformulation according to claim 2, characterized in that: The Fe3O4@SiO2-Cu and the carrier drug ilisimol ES in step S4 are dispersed in oxygen-free distilled water and the ultrasonic vibration time is 18-22 minutes.

8. Use of the magnetic effect-triggered intelligent copper-releasing nanoformulation as claimed in claim 1 in the preparation of drugs for treating tumors.

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