A mitochondrial-targeted copper ion consumption nanoparticle and its preparation method

Abstract

The present invention discloses a mitochondrial-targeted copper ion depletion nanoparticle and a preparation method thereof. By weight percentage, the components and contents of the nanoparticles are respectively: 88.91-91.93% of aminated mesoporous silica, 0.72-1.73% of (3-propylcarboxyl)triphenylphosphine bromide, 3.02-5.11% of 4-bromo-1,8-naphthalene anhydride, and 3.32-5.26% of dimethylpyridinium, and the sum of the contents of each component is 100%. The present invention modifies dimethylpyridinium and 4-bromo-1,8-naphthalene anhydride onto the surface of aminated mesoporous silica, and simultaneously modifies (3-propylcarboxyl)triphenylphosphine bromide on the surface to target mitochondria. The nanoparticles of the present invention integrate multiple functions such as mitochondrial targeting, copper depletion visualization, and drug delivery, and can be used for collaborative cancer treatment.

Description

Technical Field

[0001] The present invention belongs to the technical field of nanomaterials, and in particular relates to mitochondria-targeted copper ion-consuming nanoparticles and a preparation method thereof. Background Art

[0002] Copper is an essential nutrient for the human body, participating in cell proliferation and death by regulating a range of cellular physiological activities. Compared to normal cells, cancer cells require higher amounts of copper to support their rapid proliferation and biological activity, making them more susceptible to changes in intracellular copper levels. Mitochondrial copper depletion, in particular, shifts metabolism from respiration to glycolysis and reduces energy production, effectively and specifically combating cancer types that rely on oxidative phosphorylation. Therefore, altering mitochondrial copper levels could be an effective approach for cancer treatment. However, research in this area is still in its infancy, and the few reported studies have primarily focused on "copper depletion" strategies for cancer treatment. However, due to the complexity of tumors, single copper depletion therapies have not yielded satisfactory results. Furthermore, existing copper chelators are either too toxic or too ineffective for cancer treatment. Furthermore, due to a lack of targeting, they cannot be precisely delivered to mitochondria, resulting in low efficiency. Therefore, the design of safe and effective copper-depleting particles that target mitochondria is crucial. Summary of the Invention

[0003] The present invention aims to provide safe and effective mitochondrial-targeted copper ion-depleting nanoparticles and their preparation method. The nanoparticles are modified with dimethylpyridylamine (DPA) and 4-bromo-1,8-naphthylic anhydride (BNA) onto the surface of amino-modified mesoporous silica (MSN-NH2). The MSN-NH2 surface is also modified with the mitochondrial targeting molecule (3-propylcarboxyl)triphenylphosphonium bromide (TPP) to achieve mitochondrial targeting.

[0004] The mitochondrial-targeted copper ion depletion nanoparticles (MSN-TPP / BNA-DPA) provided by the present invention are composed of amino-modified mesoporous silica, (3-propylcarboxyl)triphenylphosphine bromide, 4-bromo-1,8-naphthalene anhydride and dimethylpyridinamine. The contents of the components are as follows by weight: 88.91-91.93% of amino-modified mesoporous silica, 0.72-1.73% of (3-propylcarboxyl)triphenylphosphine bromide, 3.02-5.11% of 4-bromo-1,8-naphthalene anhydride and 3.32-5.26% of dimethylpyridinamine, and the total content of the components is 100%.

[0005] Preferably, the average particle size of the mitochondria-targeted copper ion-consuming nanoparticles is 100 to 140 nm.

[0006] The method for preparing the mitochondria-targeted copper ion-consuming nanoparticles of the present invention comprises the following steps:

[0007] 1) Preparation of mesoporous silica nanoparticles: Octadecyltrimethoxysilane (C 18 TMS) and tetraethyl orthosilicate (TEOS) are reacted, and after the reaction is completed, the resulting precipitate is collected by filtration, washed, filtered, dried, and calcined to obtain mesoporous silica nanoparticles (MSN);

[0008] 2) Surface amination treatment of mesoporous silica nanoparticles: mesoporous silica nanoparticles and toluene are mixed under stirring conditions, and then 3-aminopropyltriethoxysilane (APTES) is added dropwise to the mixed solution. The mixture is refluxed and, after completion of the reaction, centrifuged, washed, and vacuum-dried to obtain amination-modified mesoporous silica.

[0009] 3) Synthesis of 4-bromo-1,8-naphthalene anhydride-modified mesoporous silica nanoparticles (MSN-BNA): Aminated mesoporous silica, ethanol, and 4-bromo-1,8-naphthalene anhydride were mixed under stirring and refluxed. After the reaction, the mixture was centrifuged, washed, and vacuum-dried to obtain 4-bromo-1,8-naphthalene anhydride-modified mesoporous silica nanoparticles.

[0010] 4) Synthesis of mesoporous silica nanoparticles functionalized with 4-bromo-1,8-naphthalene anhydride and dimethylpyridinamine (MSN-BNA-DPA): The mesoporous silica nanoparticles modified with 4-bromo-1,8-naphthalene anhydride prepared in step 3) were mixed with toluene and dimethylpyridinamine under stirring, and the mixture was refluxed. After the reaction was completed, the mixture was centrifuged, washed, and dried under vacuum to obtain mesoporous silica nanoparticles functionalized with 4-bromo-1,8-naphthalene anhydride and dimethylpyridinamine;

[0011] 5) Synthesis of mitochondrial-targeted copper ion-depleting nanoparticles: (3-Propanylcarboxyl)triphenylphosphine bromide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) were dissolved in an aqueous solution of DMSO and stirred in the dark at room temperature. Then, N-hydroxysuccinimide (NHS) was added and continued to stir. Then, 4-bromo-1,8-naphthalene anhydride and dimethylpyridylamine-functionalized mesoporous silica nanoparticles prepared in step 4) were added, and the reaction was continued to stir. After the reaction was completed, the mixture was centrifuged, washed, and vacuum-dried to obtain the mitochondrial-targeted copper ion-depleting nanoparticles.

[0012] Preferably, in step 1), the deionized water, ethanol, NH3·H2O, C 18 The volume ratio of TMS and TEOS is (50-150):(350-800):(13-50):(1.1-3):(2.3-6); the reaction time is 4-8 hours; the calcination temperature is 500-650° C., and the calcination time is 4-12 hours.

[0013] Preferably, in step 2), the ratio of the mass of the mesoporous silica nanoparticles to the volume of toluene is (100-700) mg: (10-80) mL; the ratio of the mass of the mesoporous silica nanoparticles to the volume of APTES is (100-700) mg: (0.2-2) mL; the reflux temperature is 80-115° C., and the reflux time is 12-48 h.

[0014] Preferably, in the step 3), the ratio of the mass of the amino-modified mesoporous silica to the volume of ethanol is (50-250) mg:(6-40) mL; the mass ratio of the amino-modified mesoporous silica to 4-bromo-1,8-naphthalene anhydride is (50-250):(7-50); the reflux temperature is 60-80°C, and the reflux time is 12-48 h.

[0015] Preferably, in step 4), the volume ratio of toluene to dimethylpyridinium is (10-80):(0.02-0.2); the ratio of the mass of 4-bromo-1,8-naphthalene anhydride-modified mesoporous silica nanoparticles to the volume of dimethylpyridinium is (46-242) mg:(20-200) μL; the reflux temperature is 80-115° C., and the reflux time is 12-48 h.

[0016] Preferably, in step 5), the mass ratio of (3-propylcarboxyl)triphenylphosphonium bromide to EDC is 2-5:1-2; the mass ratio of mesoporous silica nanoparticles functionalized with 4-bromo-1,8-naphthalene anhydride and dimethylpyridiniumamine to (3-propylcarboxyl)triphenylphosphonium bromide is (42-220):(50-150); the mass concentration of DMSO in the aqueous solution is 2-10%; the ratio of the mass of (3-propylcarboxyl)triphenylphosphonium bromide to the volume of the aqueous solution of DMSO is (50-150) mg:(20-60) mL; the stirring time in the dark is 8-24 h; the ratio of the mass of NHS to the volume of the aqueous solution of DMSO is (20-80) mg:(10-60) mL; the stirring time is continued for 4-12 h; and the stirring reaction time is continued for 8-24 h.

[0017] Principles and beneficial effects of the present invention:

[0018] The mitochondrial-targeted copper ion-depleting nanoparticles of the present invention integrate multiple functions such as mitochondrial targeting, copper depletion visualization and drug delivery, and can be used for collaborative cancer treatment. In addition to having the advantages of inorganic materials and mesoporous materials, mesoporous silica (MSN) also has the characteristics of synthetic controllable, good biocompatibility, and easy surface modification. DPA has an excellent chelating effect on copper, and its structure is stable and no dangerous chemical reactions will occur. When BNA is combined with DPA, it will emit green fluorescence when UV excitation. More importantly, when copper ions are combined with DPA, the fluorescence of BNA is quenched due to the paramagnetism of copper ions, thereby providing visual feedback of copper depletion. Taking advantage of the easy modification of the MSN-NH2 surface, BNA and DPA are modified to the MSN surface, and the mitochondrial targeting molecule TPP is modified on the MSN surface at the same time to target the mitochondria, and the fluorescence quenching properties of BNA-DPA can be used to observe the mitochondria and copper consumption in the cell. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 TEM image of the mitochondria-targeted copper ion-depleting nanoparticles prepared in Example 1;

[0020] Figure 2 This is the element distribution map of the mitochondria-targeted copper ion-depleting nanoparticles prepared in Example 1;

[0021] Figure 3 This is a Fourier transform infrared spectrum of the mitochondria-targeted copper ion-depleting nanoparticles prepared in Example 1;

[0022] Figure 4 This is a thermogravimetric analysis graph of the mitochondria-targeted copper ion-consuming nanoparticles prepared in Example 1;

[0023] Figure 5 This is a graph showing nitrogen adsorption and desorption of the mitochondria-targeted copper ion-consuming nanoparticles prepared in Example 1 and their pore size distribution;

[0024] Figure 6 This is a graph showing the copper ion chelation efficiency of the mitochondria-targeted copper ion-consuming nanoparticles prepared in Example 1;

[0025] Figure 7 This is a color wavelength diagram of the mitochondria-targeted copper ion-consuming nanoparticles prepared in Example 1;

[0026] Figure 8 This is a mitochondrial targeting diagram of the mitochondrial-targeted copper ion-depleting nanoparticles prepared in Example 1. DETAILED DESCRIPTION

[0027] Example 1

[0028] Preparation of MSN-TPP / BNA-DPA:

[0029] 1) At room temperature and under magnetic stirring, 2.5 mL of C 18 TMS and 5.3 mL of TEOS were reacted for 6 hours. The resulting precipitate was collected by filtration and washed three times with deionized water and ethanol. The filtered product was then dried at 60°C and calcined at 550°C for 6 hours to obtain mesoporous silica nanoparticles (MSNs).

[0030] 2) Under vigorous magnetic stirring, 600 mg of MSN and 60 mL of toluene were added to a 250 mL round-bottom flask. Subsequently, 1.6 mL of APTES was added dropwise to the mixture, and the mixture was reacted at 110°C for 24 h. The mixture was then centrifuged at 10,000 rpm for 10 min, washed three times with ethanol, and dried to obtain MSN-NH2.

[0031] 3) Under vigorous magnetic stirring, 200 mg of MSN-NH2, 30 mL of ethanol, and 35 mg of BNA were added to a round-bottom flask and reacted at 70°C for 24 h. The mixture was then centrifuged at 10,000 rpm for 10 min, washed three times with ethanol, and dried to obtain MSN-BNA.

[0032] 4) Under vigorous magnetic stirring, 193 mg of MSN-BNA, 60 mL of toluene, and 150 μL of DPA were added to a round-bottom flask, and the mixture was heated to 110°C for 24 h. The mixture was then centrifuged at 10,000 rpm for 10 min, washed twice with toluene and twice with ethanol, and dried to obtain MSN-BNA-DPA.

[0033] 5) Dissolve 125 mg of TPP and 125 mg of EDC in 50 mL of 5% DMSO solution and stir at room temperature in the dark for 15 h. Then, add 75 mg of NHS to the mixture and continue stirring for 5 h. Then, add 180 mg of MSN-BNA-DPA and stir at room temperature for 12 h. Centrifuge at 10,000 rpm for 10 min, wash three times with deionized water, and vacuum dry to obtain MSN-TPP / BNA-DPA.

[0034] Figure 1 This is a microscopic morphology of the mitochondria-targeted copper ion consumption nanoparticles prepared in this example. Figure 1 It can be seen that the nanoparticles are spherical in shape, have obvious pore structure, are uniform in size, and have a particle size of about 122 nm.

[0035] Figure 2 : is the element distribution diagram of MSN-TPP / BNA-DPA prepared in this embodiment. Figure 2It can be seen that Si, O, P, and N elements are uniformly distributed in the particles, indicating the successful modification of BNA, DPA, and TPP molecules.

[0036] Figure 3 : This is the Fourier transform infrared spectrum of MSN, MSN-NH2, MSN-BNA, MSN-BNA-DPA and MSN-TPP / BNA-DPA prepared in this embodiment. Figure 3 It can be seen that the 2960 cm -1 The stretching vibration of NH2 at 1683 cm in MSN-BNA and MSN-BNA-DPA proves that MSN is successfully aminated. -1 NC=O group at 1552cm -1 The vibration peaks of the CN groups at 1437 cm-1 and 1447 cm-2 respectively prove the successful modification of BNA and DPA. The stretching vibration of the CP bond in MSN-TPP / BNA-DPA appears at 1437 cm-1. -1 , indicating the modification of TPP molecules on the particles.

[0037] Figure 4 Thermogravimetric analysis curves of MSN-NH2, MSN-BNA, MSN-BNA, MSN-BNA-DPA, and MSN-TPP / BNA-DPA prepared in this example are shown. The calculated proportions of TPP, BNA, and DPA are 1.06%, 3.58%, and 3.62%, respectively.

[0038] Figure 5 The nitrogen adsorption and desorption curve and pore size distribution of MSN-TPP / BNA-DPA prepared in this example are shown in Figure 1. The nitrogen adsorption and desorption curve is IVH1 type, and the specific surface area is 576.08m 2 / g, pore volume 0.79cm 3 / g, with an average pore size of 3.7nm, concentrated at 2.81nm, and a high specific surface area and pore volume, providing a good basis for subsequent modification and drug loading.

[0039] Figure 6 : is a comparison chart of the copper adsorption efficiency of MSN-TPP / BNA-DPA and MSN prepared in this embodiment. Figure 6 It can be seen that the adsorption efficiency of MSN-TPP / BNA-DPA is significantly higher than that of MSN, and the adsorption equilibrium is reached in about 36h, and its maximum adsorption efficiency is about 24.82μg / mg.

[0040] Figure 7 It is the color wavelength diagram of MSN-TPP / BNA-DPA prepared in this embodiment. Figure 7It can be seen that the fluorescence spectrum of MSN-TPP / BNA-DPA shows a maximum emission band at 548 nm under the excitation of light with a wavelength of 406 nm, which indicates that MSN-TPP / BNA-DPA has excellent fluorescence properties. At the same time, when copper ions are coordinated with DPA, the fluorescence of BNA is still quenched because the paramagnetic properties of copper ions may cause non-radiative decay of the BNA excited state, thereby causing significant fluorescence quenching.

[0041] Figure 8 This is a mitochondrial targeting image of MSN-TPP / BNA-DPA prepared in this example. The scale is 50 μm. DAPI stains the nucleus to emit blue fluorescence, MSN-TPP / BNA-DPA emits green fluorescence, and Mito-tracker Red stains the mitochondria to emit red fluorescence. It can be clearly seen from the figure that the green fluorescence emitted by MSN-BNA-DPA does not overlap with the red fluorescence emitted by Mito-tracker Red, so MSN-BNA-DPA cannot target mitochondria. In contrast, the green fluorescence emitted by MSN-TPP / BNA-DPA completely overlaps with the red fluorescence emitted by Mito-tracker Red, and a distinct yellow color appears in the merged image, confirming that MSN-TPP / BNA-DPA can target mitochondria.

[0042] Example 2

[0043] 1) At room temperature and under magnetic stirring, 1.1 mL of C 18 TMS and 2.3 mL of TEOS were reacted for 4 hours. The resulting precipitate was collected by filtration and washed three times with deionized water and ethanol. The filtered product was then dried at 30°C and calcined at 500°C for 12 hours to obtain mesoporous silica nanoparticles (MSNs).

[0044] 2) Under vigorous magnetic stirring, 100 mg of MSN and 10 mL of toluene were added to a round-bottom flask. Subsequently, 0.2 mL of APTES was added dropwise to the mixture, and the mixture was reacted at 80°C for 48 h. The mixture was then centrifuged at 10,000 rpm for 10 min, washed three times with ethanol, and dried to obtain MSN-NH2.

[0045] 3) Under vigorous magnetic stirring, 50 mg of MSN-NH2, 6 mL of ethanol, and 7 mg of BNA were added to a round-bottom flask and reacted at 80°C for 48 h. The mixture was then centrifuged at 10,000 rpm for 10 min, washed three times with ethanol, and dried to obtain MSN-BNA.

[0046] 4) Under vigorous magnetic stirring, 46 mg of MSN-BNA, 10 mL of toluene, and 20 μL of DPA were added to a round-bottom flask, and the mixture was heated to 80°C for 48 h. The mixture was then centrifuged at 10,000 rpm for 10 min, washed twice with toluene and twice with ethanol, and dried to obtain MSN-BNA-DPA.

[0047] 5) Dissolve 50 mg of TPP and 10 mg of EDC in 20 mL of 2% DMSO solution and stir at room temperature in the dark for 24 hours. Then, add 20 mg of NHS to the mixture and continue stirring for 5 hours. Then, add 42 mg of MSN-BNA-DPA and stir at room temperature for 24 hours. Then, centrifuge at 10,000 rpm for 10 minutes, wash three times with deionized water, and vacuum dry to obtain MSN-TPP / BNA-DPA.

[0048] The particle size obtained in this embodiment is about 100 nm, and the proportions of TPP, BNA, and DPA are 1.73%, 3.02%, and 3.32%, respectively.

[0049] Example 3

[0050] 1) At room temperature and under magnetic stirring, 3 mL of C 18 TMS and 6 mL of TEOS were reacted for 6 hours. The resulting precipitate was collected by filtration and washed three times with deionized water and ethanol. The filtered product was then dried at 60°C and calcined at 650°C for 4 hours to obtain mesoporous silica nanoparticles (MSNs).

[0051] 2) Under vigorous magnetic stirring, 700 mg of MSN and 80 mL of toluene were added to a 250 mL round-bottom flask. Subsequently, 2 mL of APTES was added dropwise to the mixture, followed by reaction at 115°C for 12 h. The mixture was then centrifuged at 10,000 rpm for 10 min, washed three times with ethanol, and dried to obtain MSN-NH2.

[0052] 3) Under vigorous magnetic stirring, 250 mg of MSN-NH2, 40 mL of ethanol, and 50 mg of BNA were added to a round-bottom flask and reacted at 80°C for 12 h. The mixture was then centrifuged at 10,000 rpm for 10 min, washed three times with ethanol, and dried to obtain MSN-BNA.

[0053] 4) Under vigorous magnetic stirring, 242 mg of MSN-BNA, 80 mL of toluene, and 200 μL of DPA were added to a round-bottom flask, and the mixture was heated to 115°C for 12 h. The mixture was then centrifuged at 10,000 rpm for 10 min, washed twice with toluene and twice with ethanol, and dried to obtain MSN-BNA-DPA.

[0054] 5) Dissolve 150 mg of TPP and 60 mg of EDC in 60 mL of 10% DMSO solution and stir at room temperature in the dark for 8 h. Then, add 80 mg of NHS to the mixture and continue stirring for 4 h. Then, add 220 mg of MSN-BNA-DPA and stir at room temperature for 8 h. Centrifuge at 10,000 rpm for 10 min, wash three times with deionized water, and vacuum dry to obtain MSN-TPP / BNA-DPA.

[0055] The particle size obtained in this embodiment is about 140 nm, and the proportions of TPP, BNA, and DPA are 0.72%, 5.11%, and 5.26%, respectively.

[0056] The above-described embodiments merely represent a number of embodiments of the present invention. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, and these variations and improvements fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A mitochondrial-targeted copper ion depletion nanoparticle, characterized in that: The nanoparticles are composed of amino mesoporous silica, (3-propylcarboxyl)triphenylphosphine bromide, 4-bromo-1,8-naphthalene anhydride and dimethylpyridinamine; the contents of each component are as follows by weight percentage: 88.91-91.93% of amino mesoporous silica, 0.72-1.73% of (3-propylcarboxyl)triphenylphosphine bromide, 3.02-5.11% of 4-bromo-1,8-naphthalene anhydride, and 3.32-5.26% of dimethylpyridinamine, and the sum of the contents of each component is 100%; The mitochondria-targeted copper ion-consuming nanoparticles are prepared by a preparation method comprising the following steps: 1) Preparation of mesoporous silica nanoparticles: Octadecyltrimethoxysilane and ethyl orthosilicate were sequentially added to a mixed solution of deionized water, ethanol, and NH3·H2O under stirring at room temperature to react. After the reaction, the resulting precipitate was collected by filtration, washed, filtered, dried, and then calcined to obtain mesoporous silica nanoparticles. 2) Surface amination treatment of mesoporous silica nanoparticles: mesoporous silica nanoparticles and toluene are mixed under stirring conditions, and then 3-aminopropyltriethoxysilane is added dropwise to the mixed solution. The mixture is refluxed and, after completion of the reaction, centrifuged, washed, and vacuum-dried to obtain amination-modified mesoporous silica. 3) Synthesis of 4-bromo-1,8-naphthalene anhydride-modified mesoporous silica nanoparticles: Aminated mesoporous silica, ethanol, and 4-bromo-1,8-naphthalene anhydride were mixed under stirring and refluxed. After the reaction, the mixture was centrifuged, washed, and vacuum-dried to obtain 4-bromo-1,8-naphthalene anhydride-modified mesoporous silica nanoparticles. 4) Synthesis of mesoporous silica nanoparticles functionalized with 4-bromo-1,8-naphthalene anhydride and dimethylpyridinamine: The 4-bromo-1,8-naphthalene anhydride-modified mesoporous silica nanoparticles prepared in step 3) were mixed with toluene and dimethylpyridinamine under stirring, and the mixture was refluxed. After the reaction was completed, the mixture was centrifuged, washed, and vacuum-dried to obtain mesoporous silica nanoparticles functionalized with 4-bromo-1,8-naphthalene anhydride and dimethylpyridinamine; 5) Synthesis of mitochondrial-targeted copper ion-depleting nanoparticles: (3-Propanylcarboxyl)triphenylphosphine bromide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were dissolved in an aqueous solution of DMSO and stirred in the dark at room temperature. Then, N-hydroxysuccinimide was added and continued to stir. Then, 4-bromo-1,8-naphthalene anhydride and dimethylpyridylamine-functionalized mesoporous silica nanoparticles prepared in step 4) were added and continued to stir. After the reaction, the mixture was centrifuged, washed, and vacuum-dried to obtain the mitochondrial-targeted copper ion-depleting nanoparticles.

2. The mitochondria-targeted copper ion depletion nanoparticles according to claim 1, characterized in that: The average particle size of the nanoparticles is 100-140 nm.

3. The mitochondria-targeted copper ion depletion nanoparticles according to claim 1, characterized in that: In the step 1), the volume ratio of deionized water, ethanol, NH3·H2O, octadecyltrimethoxysilane and ethyl orthosilicate is (50-150):(350-800):(13-50):(1.1-3):(2.3-6); the reaction time is 4-8 h; the calcination temperature is 500-650°C, and the calcination time is 4-12 h.

4. The mitochondria-targeted copper ion depletion nanoparticles according to claim 1, characterized in that: In step 2), the ratio of the mass of the mesoporous silica nanoparticles to the volume of toluene is (100-700) mg: (10-80) mL; the ratio of the mass of the mesoporous silica nanoparticles to the volume of 3-aminopropyltriethoxysilane is (100-700) mg: (0.2-2) mL; the reflux temperature is 80-115° C., and the reflux time is 12-48 h.

5. The mitochondria-targeted copper ion depletion nanoparticles according to claim 1, characterized in that: In the step 3), the mass ratio of the amino-modified mesoporous silica to the volume of ethanol is (50-250) mg: (6-40) mL; the mass ratio of the amino-modified mesoporous silica to 4-bromo-1,8-naphthalene anhydride is (50-250): (7-50); the reflux temperature is 60-80° C., and the reflux time is 12-48 h.

6. The mitochondria-targeted copper ion depletion nanoparticles according to claim 1, characterized in that: In step 4), the volume ratio of toluene to dimethylpyridinium is (10-80):(0.02-0.2); the mass ratio of 4-bromo-1,8-naphthalene anhydride-modified mesoporous silica nanoparticles to the volume ratio of dimethylpyridinium is (46-242) mg:(20-200) μL; the reflux temperature is 80-115°C, and the reflux time is 12-48 h.

7. The mitochondria-targeted copper ion depletion nanoparticles according to claim 1, characterized in that: In the step 5), the mass ratio of (3-propylcarboxyl)triphenylphosphonium bromide to 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride is (2-5):(1-2); the mass ratio of mesoporous silica nanoparticles functionalized with 4-bromo-1,8-naphthalene anhydride and dimethylpyridinamine to (3-propylcarboxyl)triphenylphosphonium bromide is (42-220):(50-150); the mass concentration of DMSO in the aqueous solution is 2-10%; the mass ratio of (3-propylcarboxyl)triphenylphosphonium bromide to the volume of the aqueous DMSO solution is (50-150) mg:(20-60) mL; the stirring time in the dark is 8-24 h; the mass ratio of N-hydroxysuccinimide to the volume of the aqueous DMSO solution is (20-80) mg:(10-60) mL; the stirring time is continued for 4-12 h; and the stirring reaction time is continued for 8-24 h.

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