A mesoporous fe 0 Method for enhancing activity of gallic acid using mesoporous fe nanomaterial and applications thereof

Abstract

The application discloses a kind of by mesoporous Fe 0 Nanometer material enhances the method for activity of gallic acid and application thereof.The present application fixes gallic acid (GA) with redox activity in mesoporous zero-valent iron nanoparticles (Fe 0 NPs), and then encapsulated by SiO2 outer layer containing disulfide bond (denoted as Fe 0 @GA-ss-SiO2NPs). With the help of intracellular glutathione, oxygen molecules are activated by electron transfer, and a large amount of O2 ·‑ And H2O2 are spontaneously generated, and the sustained high concentration of Fe 0 Fe 2+ Further catalyzes the decomposition of H2O2, and generates highly oxidized ·OH free radicals. At the same time, GA quinone derivatives produce 1 O2 by Russel mechanism. In vitro cell experiments confirm that the nanometer material can cause cancer cell ferroptosis, and exhibits high-efficiency cancer cell killing effect at ultra-low dose.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a method utilizing mesoporous Fe 0 Methods and applications of nanomaterials to enhance the activity of gallic acid. Background Technology

[0002] Gallic acid is a polyphenolic organic compound found ubiquitously in plants in nature and is safe and beneficial to organisms. Polyphenol species possess numerous potential health benefits. There is ample evidence that certain polyphenols exert numerous beneficial effects through their antioxidant activity, protecting the body from various diseases, such as cancer and cardiovascular disease. Gallic acid is a key bioactive component of green tea, and gallic acid extracted from tea leaves has been shown to possess various biological and pharmaceutical functions, such as anti-fatigue, antibacterial, anticancer, and anti-angiogenic effects. The quinones and semiquinones formed by the autoxidation of gallic acid have the function of accelerating electron transfer during electron transfer processes. Simultaneously, the formed quinones can convert H₂O₂ into… 1 O2 (Equation 1).

[0003] Chemokinetic therapy (CDT) is a novel cancer treatment approach that has emerged in recent years. CDT utilizes the Fenton reaction, with ferrous ions acting as a catalyst, to convert H₂O₂ into highly oxidized ·OH (Equation 2). Among common ROS, ·OH possesses the strongest oxidizing power (E(·OH / H₂O) = 2.80V, E( 1 With E(H2O2 / H2O) = 2.17V and E(H2O2 / H2O) = 1.78V, the Fenton reaction has proven to be an effective strategy for inducing cancer cell death by utilizing the high levels of endogenous hydrogen peroxide expressed in most tumors. Therefore, we employed zero-valent iron (Fe2O3 / H2O) as an example. 0 The material, acting as a carrier for GA, can activate oxygen molecules as an electron donor to generate a large amount of H2O2 (Equation 3), releasing Fe... 2+ ·OH can be efficiently generated via the Fenton reaction. It is worth noting that gallic acid reacts with ferrous ions (Fe... 2+ The complexation reaction of iron-gallic acid (Fe-GA) is the key chemical reaction in the preparation of ink, forming a blue-violet iron-gallic acid (Fe-GA) metal complex. Interestingly, this iron coordination compound exhibits high reducing power; it can donate electrons from the gallate ligand to surrounding free oxygen molecules, reducing oxygen (O2) to superoxide anion (O2⁻). ·-The presence of ferrous ions and hydrogen peroxide (H2O2) (Equation 4) increases the intratumoral H2O2 content, leading to the generation of large amounts of ·OH within the tumor and inducing ferroptosis. Ferrroptosis is a necrotic cell death mechanism catalyzed by ferrous ions. It is characterized by the inactivation of the intracellular reducing system, resulting in the oxidation of lipid molecules containing polyunsaturated fatty acids located on the intracellular membrane by reactive oxygen species (ROS). The accumulation of these lipid peroxides ultimately causes cell membrane rupture, increasing intracellular ROS levels and inducing tumor cell death.

[0004] Q + 2H₂O₂ → Q + 2H₂O + 1 O2 (1)

[0005] Fe 2+ +H₂O₂→Fe 3+ +.OH+OH - (2)

[0006] O2+Fe 0 +2H + →Fe 2+ +H2O2 (3)

[0007] O2 + Fe → GA + 2H+ + →Fe-GA+H2O2 (4)

[0008] The inventors conducted the following searches regarding the relevant content of this application:

[0009] 1. Search results from http: / / scholar.glgoo.com / (January 24, 2024)

[0010] Search keywords Search results <![CDATA[Patent Fe 0 Enhancing the anti-cancer activity of gallic acid]]> none <![CDATA[Patented gallic acid-modified Fe 0 nanoparticles]]> none Gallic acid promotes the generation of reactive oxygen species. none

[0011] 2. Search results from CNKI (China National Knowledge Infrastructure): (2024 / 01 / 24)

[0012] Search Method 1:

[0013] Title-----Fe 0 0 items enhancing the anticancer activity of gallic acid.

[0014] Title: Gallic Acid Modified Fe 0 0 nanoparticles.

[0015] Title: Promoting gallic acid-mediated singlet oxygen generation (0 items).

[0016] Search Method Two:

[0017] Full text-----Fe 0 0 items enhancing the anticancer activity of gallic acid.

[0018] Full text ----- Gallic acid-modified Fe 0 Eleven nanoparticles were not relevant to this method.

[0019] The full text of 1014 items promoting gallic acid-mediated singlet oxygen generation is irrelevant to this method.

[0020] Search Method 3:

[0021] Keywords: gallic acid; 4200 items, none of which are relevant to this method.

[0022] Keywords: Oxygen activation efficiency (19 items), none of which are relevant to this method.

[0023] Keywords: Singlet oxygen (954 terms), none of which are relevant to this method. Summary of the Invention

[0024] Therefore, the present invention aims to provide a method utilizing mesoporous Fe 0 Methods and applications of nanomaterials to enhance the activity of gallic acid.

[0025] Nano-zero valent iron (Fe) 0 The strong reducing properties of gallic acid (3,4,5-trihydroxybenzoic acid, GA) enable it to act as an electron donor, undergoing molecular oxygen activation to produce large amounts of ROS. Simultaneously, gallic acid (3,4,5-trihydroxybenzoic acid, GA) reacts with ferrous ions (Fe... 2+ This formed a bluish-purple iron-gallic acid (Fe) 3+ -GA) metal complexes, these iron coordination compounds also possess high reducing properties; they can donate electrons from gallate ligands to surrounding free oxygen molecules, reducing oxygen (O2) to superoxide anions (O2). ·- ) and hydrogen peroxide (H2O2). Utilizing Fe 0 and Fe 3+ -GA activates oxygen to produce H2O2, and gallic acid quinone derivatives convert H2O2 into H2O2 via the Russell Machinesm. 1 O2. The synergistic effect of these two substances activates the anticancer ability of gallic acid. More importantly, this inorganic-organic hybrid nanomaterial also exhibits excellent oxygen activation ability even under low-dose application. Therefore, this invention introduces GA into Fe... 0 The enhanced anticancer activity of gallic acid was achieved in the porous structure.

[0026] This invention utilizes mesoporous Fe 0 A method to enhance the activity of gallic acid using nanomaterials involves immobilizing gallic acid (GA), which has redox activity, onto mesoporous zero-valent iron nanoparticles (Fe). 0In NPs), Fe is further encapsulated through an outer layer of SiO2 containing disulfide bonds to obtain Fe. 0 @GA-ss-SiO2 nanomaterials.

[0027] Specifically, the steps include the following:

[0028] Step 1: Monodisperse Fe 0 Preparation of nanomaterials

[0029] Under a nitrogen atmosphere, dilute sulfuric acid solution (pH = 2.31 ± 0.02) was added to a three-necked flask reactor. 20.1 mg of ferrous sulfate heptahydrate and 76 mg of hexadecyltrimethylammonium bromide were weighed, dissolved thoroughly with ultrasonic assistance using dilute sulfuric acid solution (pH = 2.31 ± 0.02), and then added to the reactor, where the mixture was stirred and dispersed evenly. 14.5 mg of sodium borohydride was weighed, dissolved thoroughly with dilute sulfuric acid solution (pH = 2.31 ± 0.02), and then added dropwise to the three-necked flask. The solution in the flask quickly turned black. The mixture was stirred and dispersed for another 3 minutes. The black solution in the three-necked flask was removed, immediately centrifuged, and the precipitate was collected. The precipitate was washed three times with anhydrous ethanol and dried under vacuum at room temperature to obtain black Fe. 0 Nanomaterials. The Fe prepared in this step... 0 Nanomaterials, with a size of about 40nm-60nm.

[0030] Step 2: Monodisperse Fe 0 Preparation of @GA nanomaterials

[0031] 2.4mg Fe 0 16 mg of GA was dissolved in 5 mL of anhydrous ethanol, and labeled as solution 1 and solution 2, respectively. After ultrasonic dispersion, solution 1 was slowly added dropwise to solution 2, and the reaction was carried out with magnetic stirring at room temperature for 6 h. After the reaction was completed, the mixture was immediately centrifuged and the precipitate was collected, washed with anhydrous ethanol, and dried under vacuum at room temperature to obtain black Fe. 0 @GA Nanomaterials.

[0032] Step 3: Monodisperse Fe 0 Preparation of @GA-ss-SiO2 nanomaterials

[0033] Weigh out 5mg Fe 0 @GA nanomaterials and 5mg DSPE-mPEG 2000Add the solution to a glass bottle, then add anhydrous ethanol and sonicate until homogeneous. Add 3.75 mL of deionized water and 400 μL of ammonia (5.38 mol / L) to the glass bottle and sonicate until homogeneous. Add 3.5 μL of tetraethyl silicate (TEOS) and 1.4 μL of bis-[3-(triethoxysilyl)propyl]-disulfide (BTSPD) to the glass bottle and sonicate for 5 min. Add 0.2 μL of bis-[3-(triethoxysilyl)propyl]-tetrasulfide (BTESPD) and sonicate for 2 h. After the reaction is complete, immediately centrifuge and collect the precipitate. Wash with anhydrous ethanol and vacuum dry at room temperature to obtain Fe. 0 @GA-ss-SiO2 nanomaterials.

[0034] This invention utilizes a SiO2 shell containing disulfide bonds to support Fe 0 @GA nanomaterials are used for coating to improve Fe 0 The invention aims to improve the biocompatibility of @GA nanomaterials and their specific response to cancer cells in subsequent tumor treatment. By optimizing the ratio of silicon and sulfur sources, the invention ultimately determined the parameters to ensure a silica shell of suitable thickness after encapsulation.

[0035] Furthermore, the present invention uses an equal amount of Fe 0 Nanomaterials to replace Fe 0 @GA nanomaterials, preparation of Fe 0 -ss-SiO2 nanomaterials were compared and investigated.

[0036] This invention Fe 0 Application of @GA-ss-SiO2 nanomaterials in the preparation of anti-tumor drug formulations.

[0037] This invention Fe 0 Application of @GA-ss-SiO2 nanomaterials in the preparation of ROS inducers.

[0038] This invention Fe 0 @GA-ss-SiO2 nanomaterials can specifically respond to the tumor microenvironment and generate high levels of ROS within tumor cells.

[0039] This invention is based on mesoporous Fe 0 The reason why the introduction of gallic acid into nanomaterials has a good ability to generate ROS is due to Fe. 0 Gallic acid enhances its anticancer activity primarily through the following three pathways:

[0040] Approach 1: Fe 0 Its strong reducing properties endow it with the ability to act as an electron donor to activate molecular oxygen and generate a large amount of ROS.

[0041] Pathway 2: Gallic acid and ferrous ions (Fe)2+ This forms a blue-violet iron-gallic acid (GA-Fe) metal complex. This iron coordination compound has high reducing power; it can donate electrons from the gallate ligand to surrounding free oxygen molecules, reducing oxygen (O2) to superoxide anion (O2). ·- ) and hydrogen peroxide (H2O2).

[0042] Pathway 3: The quinone derivatives formed by the auto-oxidation of gallic acid have the function of accelerating electron transfer during electron transfer. At the same time, the formed quinone derivatives can convert H2O2 into… through the Russell Mechanism. 1 O2.

[0043] Fe 0 @GA nanomaterials have high Fe content 0 The content and stronger ROS generation ability, and Fe 0 After being encapsulated with SiO2 containing disulfide bonds, the gallic acid in the @GA nanomaterial can generate a large amount of reactive oxygen species in cells with the help of the carrier, inducing the accumulation of lipid peroxides in cells and effectively promoting ferroptosis in tumor cells.

[0044] Compared with existing technologies, the beneficial effects of this invention are reflected in:

[0045] 1. This invention utilizes Fe 0 The porous morphology of nanomaterials allows gallic acid to be introduced into them, cleverly stimulating the anti-cancer potential of gallic acid.

[0046] 2. The Fe described in this invention 0 @GA-ss-SiO2 nanomaterials have the potential to serve as highly efficient ROS generators in tumor microenvironments. Attached Figure Description

[0047] Figure 1 It is Fe 0 Elemental mapping diagram of @GA-ss-SiO2 nanomaterials. Figure 1 The results show that the elements (O, N, Si, S) in this nanomaterial are uniformly distributed, proving that Fe... 0 Successful synthesis of @GA-ss-SiO2 nanomaterials.

[0048] Figure 2 It is a precursor Fe 0 Nanomaterials, end product Fe 0 Fourier transform infrared (FTIR) spectra of GA nanomaterials and GA (gallic acid). Figure 2 As shown, for Fe 0 @GANPs and Fe 0The Fourier transform infrared (FTIR) spectra of the NPs were compared at 1540 cm⁻¹. -1 The absorption peak near GA ( The additional absorption peak corresponding to the tensile vibration indicates that GA has been grafted onto Fe. 0 On NPs. It is worth noting that on Fe... 0 In @GANPs, GA's 1028cm -1 The absorption peak (C-OH stretching vibration of the carboxyl group) red-shifted to 1080 cm⁻¹. -1 This indicates that GA is coordinated with iron. This proves that gallic acid successfully modifies Fe. 0 Nanomaterials.

[0049] Figure 3 It is a precursor Fe 0 Nanomaterials (left), final product Fe 0 10nm deep profile X-ray photoelectron spectroscopy (XPS) of @GA nanomaterial (right). From Figure 3 It can be seen that Fe 0 Nanomaterials and Fe 0 @GA nanomaterials exhibit high Fe content at 10 nm. 0 Content, and Fe 0 @GA Nanomaterials Fe 0 The content is higher. This result indicates that Fe... 0 @GA nanomaterials Fe 0 Content higher than Fe 0 Fe nanomaterials 0 content.

[0050] Figure 4 It uses high concentrations of MB to detect Fe. 0 @GA nanomaterials generate ROS UV-Vis absorption spectrum. Figure 4 The results showed that in Fe-containing 0 The absorbance of MB detected in the nanomaterials experimental group and the GA experimental group decreased slightly, while that in Fe... 0 The absorbance of MB detected in the @GA nanomaterials experimental group decreased significantly, and the degradation rate of MB was approximately 80% after 5 minutes, indicating that Fe... 0 @GA nanomaterials have excellent ROS generation capabilities.

[0051] Figure 5 ABDA was used as an indicator to further evaluate Fe. 0 Experimental results of the singlet oxygen generation capability of @GA nanomaterials. ABDA in 1 In the presence of O2, it can interact with 1 O2 reacts, causing a decrease in the absorbance of ABDA. From Figure 5 It can be seen that Fe0 The decrease in ABDA absorbance in the @GA nanomaterials experimental group indicates that Fe 0 @GA nanomaterials have been produced 1 The ability of O2.

[0052] Figure 6 IPA (isopropyl alcohol) is used as . The UV-Vis absorption spectra of the OH scavenger during MB degradation experiments were used to investigate Fe. 0 Molecular oxygen activation products of @GA nanomaterials. From Figure 6 It is clear that the degradation of MB is significantly inhibited in the presence of IPA, indicating that Fe 0 @GA nanomaterials ROS products exist . OH.

[0053] Figure 7 The UV-Vis absorption spectrum of the MB degradation experiment using CAT (catalase) as an H2O2 scavenger was used to investigate Fe. 0 Molecular oxygen activation products of @GA nanomaterials. From Figure 7 It is clear that the degradation of MB is significantly inhibited in the presence of CAT, indicating that Fe 0 @GA nanomaterials contain H2O2 as ROS products.

[0054] Figure 8 It uses SOD (superoxide anion dismutase) as O2 ·- The UV-Vis absorption spectra of the scavenger during MB degradation experiments were used to investigate Fe. 0 Molecular oxygen activation products of @GA nanomaterials. From Figure 8 It is clear that the degradation of MB is significantly inhibited in the presence of IPA, indicating that Fe 0 @GA nanomaterials ROS products contain O2 ·- .

[0055] Figure 9 and Figure 10 They were captured by the free radical scavenger DMPO. . OH and O2 ·- The experimental results of ESR detection are shown in the figure. Figure 9 and Figure 10 As can be seen, in the presence of Fe 0 The @GA nanomaterials experimental group exhibits very strong DMPO- . The 1:2:2:1 ESR signal of OH and DMPO-O2 ·- The six-peak signal further illustrates that Fe 0 @GA nanomaterials contain ROS products. . OH and O2·- .

[0056] Figure 11 It is captured by the free radical scavenger TEMP 1 The experimental results of ESR detection for O2 are shown in the figure. Figure 11 As can be seen, in the presence of Fe 0 The @GA nanomaterials experimental group exhibits a very strong 1:1:1 ESR signal, further illustrating that Fe... 0 @GA nanomaterials contain ROS products. 1 O2.

[0057] Figure 12 By optimizing the ratio of silicon and sulfur sources, Fe was finally obtained with a silica shell of suitable thickness. 0 TEM images of @GA-ss-SiO2 nanomaterials. The ad images show 32 μL TEOS, 13 μL BTSPD; 16 μL TEOS, 6.5 μL BTSPD; 8.0 μL TEOS, 3.3 μL BTSPD; and 3.5 μL TEOS, 1.4 μL BTSPD. The BTESPD is 0.2 μL for all samples.

[0058] Figure 13 It utilizes confocal laser scanning microscopy, with DCFH-DA as the ROS detection probe; ROSRGEEN as the H2O2 probe; HPF as the ·OH detection probe; and SOSG as... 1 O2 detection probe; using DHE as O2 detection probe. ·- Probe. Used to detect intracellular total ROS, H₂O₂, ·OH, 1 O2, O2 ·- The experimental results obtained from the detection are shown in the figure. (Example) Figure 13 As shown, it can be clearly seen that in Fe 0 In the experimental group of HepG2 cells (human liver cancer cells) treated with @GA-ss-SiO2 nanomaterials, distinct green, green, green, green, and red fluorescence were observed sequentially, indicating that Fe... 0 @GA-ss-SiO2 can generate more total ROS, H2O2, and ·OH. 1 O2, O2 ·- . Detailed Implementation

[0059] The technical solution of the present invention will be further analyzed and explained through specific embodiments below.

[0060] Example 1: Preparation of the target product

[0061] 1. Fe 0 Preparation of nanomaterials

[0062] A 100 mL three-necked flask was selected, and 41 mL of dilute sulfuric acid solution (pH = 2.31) was added. The mixture was stirred for 5 min under a nitrogen atmosphere using a mechanical stirrer (300 rpm / min). 20.1 mg of ferrous sulfate heptahydrate and 76 mg of hexadecyltrimethylammonium bromide were weighed and dissolved thoroughly with dilute sulfuric acid solution (pH = 2.31) using ultrasonic assistance. The dissolved substances were then added to the three-necked flask and stirred until evenly dispersed for 5 min. 14.5 mg of sodium borohydride was weighed and dissolved thoroughly with 2 mL of dilute sulfuric acid solution (pH = 2.31). This solution was then added dropwise to the three-necked flask. The solution in the flask quickly turned black. After stirring and dispersing for another 3 min, the black solution in the three-necked flask was removed, immediately centrifuged (9000 rpm, 30 s), and the precipitate was collected. The precipitate was washed three times with anhydrous ethanol and dried under vacuum at room temperature for 8 h to obtain black Fe. 0 Nanomaterials.

[0063] 2. Fe 0 Preparation of @GA nanomaterials

[0064] Select a 10mL brown glass bottle and weigh out 2.4mg of Fe. 0 Nanomaterials and 16 mg of gallic acid were added, followed by 10 mL of anhydrous ethanol in a glass bottle. The mixture was ultrasonically dispersed and magnetically stirred at room temperature for 6 hours. After the reaction was complete, the mixture was immediately centrifuged (9000 rpm, 30 s) and the precipitate was collected. The precipitate was then vacuum dried at room temperature for 8 hours to obtain black Fe. 0 @GA Nanomaterials.

[0065] 3. Fe 0 Preparation of @GA-ss-SiO2 nanomaterials

[0066] Weigh out 5mg of Fe 0 @GA nanomaterials and 5mg DSPE-mPEG 2000 Add the solution to a glass bottle, then add anhydrous ethanol and sonicate to disperse evenly. Add 3.75 mL of deionized water and 400 μL of ammonia (5.38 mol / L) to the glass bottle and sonicate to disperse evenly. Add 3.5 μL of tetraethyl silicate (TEOS) and 1.4 μL of bis-[3-(triethoxysilyl)propyl]-disulfide (BTSPD) to the glass bottle and sonicate for 5 min. Add 0.2 μL of bis-[3-(triethoxysilyl)propyl]-tetrasulfide (BTESPD) and sonicate for 2 h. After the reaction is complete, immediately centrifuge and collect the precipitate. Wash three times with anhydrous ethanol and dry under vacuum at room temperature to obtain Fe. 0 @GA-ss-SiO2 nanomaterials.

[0067] 4. Fe 0 Preparation of -ss-SiO2 nanomaterials

[0068] Fe 0 Preparation method of -ss-SiO2 nanomaterials and Fe 0 The preparation method of @GA-ss-SiO2 nanomaterials is similar. Using equal amounts of Fe... 0 Nanomaterials to replace Fe 0 @GA Nanomaterials, other experimental procedures remain unchanged.

[0069] Example 2: Fe 0 Verification of enhanced oxidation activity of GA-ss-SiO2 nanomaterials

[0070] 1. MB degradation detection of ROS generation

[0071] Experimental group 1: Fe 0 Nanomaterials (200 μg / mL) and Fe 0 @GA nanomaterials (200 μg / mL) were dispersed in MB (15 μg / mL) solution. After reacting for 5 min, the mixture was centrifuged (10000 rpm, 1 min), and the supernatant was collected. The absorbance change at around 660 nm was detected by UV-Vis spectroscopy to investigate the effect of Fe on the absorption of Fe. 0 The degradation effect of introducing gallic acid onto nanomaterials on MB solution.

[0072] To further investigate Fe 0 Based on the above experiments, ROS-generating species of @GA nanomaterials were introduced, including ROS scavengers isopropanol (IPA, 1 mL / 4 mL), superoxide dismutase (SOD, 250 μg / mL), and catalase (CAT, 1.25 mg / mL). The type of ROS generated was determined by observing the degradation of MB.

[0073] 2. ABDA testing 1 O2 generation

[0074] Prepare ABDA (2mM, DMSO) solution. In a 10mL centrifuge tube, add 20µL of ABDA solution and 4mL of MES (pH=6.5) solution, mix thoroughly, and react at room temperature in the dark. After 10 minutes, centrifuge (10000rpm, 1min) and record the change in UV absorption intensity around 400nm.

[0075] 3. Electron Spin Resonance Spectroscopy (ESR) Detection . OH and O2 ·-

[0076] Using DMPO as the capture agent, the generated ROS was determined by ESR. . OH and O2 ·-(DMPO: 5,5-Dimethyl-1-pyrroline N-oxide, a free radical scavenger; EPR: electron spin resonance spectroscopy) This indicates that Fe... 0 @GA nanomaterials contain ROS products. . OH and O2 ·- .

[0077] Example 3: Detection of intracellular ROS

[0078] The intracellular ROS production under different treatment conditions was detected using DCFH-DA. HepG2 cells (37℃, 5% CO2) were cultured for 24 h and then treated with gallic acid (2.75 μg / mL), Fe... 0 @GA-ss-SiO2 nanomaterials (50 μg / mL) and Fe 0 -ss-SiO2 nanomaterials (50 μg / mL) were co-incubated for 12 h and washed three times with PBS. Then, DCFH-DA was added and incubated for 15 min, followed by three more washes with PBS. 1 mL of PBS was added, and fluorescence imaging was observed using a laser confocal scanning microscope.

Claims

1. A method utilizing mesoporous Fe 0 Preparation of Fe nanomaterials to enhance gallic acid activity 0 The method for using @GA-ss-SiO2 nanomaterials is characterized by: Gallic acid, which has redox activity, is immobilized in mesoporous zero-valent iron nanoparticles and then encapsulated with a SiO2 outer layer containing disulfide bonds to obtain Fe. 0 @GA-ss-SiO2 nanomaterials include the following steps: Step 1: Monodisperse Fe 0 Preparation of nanomaterials Under a nitrogen atmosphere, dilute sulfuric acid solution was added to a three-necked flask reactor. Ferrous sulfate heptahydrate and hexadecyltrimethylammonium bromide were weighed, dissolved thoroughly with ultrasonic assistance using dilute sulfuric acid solution, and then added to the reactor, stirred and dispersed evenly. Sodium borohydride was weighed, dissolved thoroughly with dilute sulfuric acid solution, and then added dropwise to the three-necked flask. The solution in the flask quickly turned black. Stirring and dispersion continued. The black solution in the three-necked flask was removed, centrifuged, and the precipitate was collected. The precipitate was washed with anhydrous ethanol and dried under vacuum at room temperature to obtain black Fe. 0 Nanomaterials; Step 2: Monodisperse Fe 0 Preparation of @GA nanomaterials Fe 0 GA and Fe were dissolved separately in anhydrous ethanol, labeled as solution 1 and solution 2, respectively. After ultrasonic dispersion, solution 1 was slowly added dropwise to solution 2, and the mixture was magnetically stirred at room temperature for 6 hours. After the reaction was completed, the mixture was immediately centrifuged and the precipitate was collected, washed with anhydrous ethanol, and vacuum dried at room temperature to obtain black Fe. 0 @GA Nanomaterials; The GA is gallic acid; Step 3: Monodisperse Fe 0 Preparation of @GA-ss-SiO2 nanomaterials Weigh Fe 0 @GA nanomaterials and DSPE-mPEG 2000 Add the precipitate to a glass bottle, then add anhydrous ethanol and sonicate to disperse it evenly. Add deionized water and ammonia to the glass bottle and sonicate to disperse it evenly. Add tetraethyl silicate and bis-[3-(triethoxysilyl)propyl]-disulfide to the glass bottle and sonicate to disperse it evenly. Add bis-[3-(triethoxysilyl)propyl]-tetrasulfide and sonicate for 2 hours. After the reaction is complete, centrifuge and collect the precipitate, wash with anhydrous ethanol, and vacuum dry at room temperature to obtain Fe. 0 @GA-ss-SiO2 nanomaterials; In step 1, the pH of the dilute sulfuric acid solution is 2.31 ± 0.02; the Fe... 0 The size of the nanomaterials is between 40nm and 60nm; In step 2, Fe 0 The amount added was 2.4 mg, and the amount added was 16 mg.

2. The method according to claim 1, characterized in that: In step 1, the mass ratio of ferrous sulfate heptahydrate to sodium borohydride is 1.386:

1.

3. The method according to claim 1, characterized in that: In step 3, Fe 0 @GA nanomaterials and DSPE-mPEG 2000 The addition amount is 5mg for all.

4. The method according to claim 1, characterized in that: In step 3, the amount of tetraethyl silicate added is 3.5 μL, the amount of bis-[3-(triethoxysilane)propyl]-disulfide added is 1.4 μL, and the amount of bis-[3-(triethoxysilane)propyl]-tetrasulfide added is 0.2 μL.

5. Fe prepared by any one of the methods in claims 1-4 0 Application of @GA-ss-SiO2 nanomaterials in the preparation of drug formulations for treating tumors, wherein the tumor is liver cancer.

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