Cobalt ferrite-platinum polyethylene glycol composite anticancer nanomaterial and preparation method thereof

By preparing cobalt ferrite@platinum polyethylene glycol composite nanomaterials and combining chemical kinetics with sonodynamic therapy, the problems of penetration depth and tolerance of existing treatment methods have been solved, achieving a highly efficient and non-invasive cancer cell killing effect in deep tissues.

CN116327935BActive Publication Date: 2026-03-24SOUTH CHINA UNIV OF TECH +1
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-04-14
Publication Date
2026-03-24

AI Technical Summary

Technical Problem

Existing cancer treatments such as chemotherapy, radiotherapy, and surgery have tolerance issues; photothermal therapy and chemodynamic therapy have limited penetration depth; the Fenton reaction has strict pH requirements; and sonodynamic therapy is not effective in deep tissues.

Method used

Cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterials were prepared by synthesizing mesoporous cobalt ferrite via a hydrothermal method and modifying its surface with platinum and polyethylene glycol. Combining chemokinetics and sonodynamic therapy, the reactive oxygen species were generated by ultrasound activation to synergistically kill cancer cells.

Benefits of technology

It achieves efficient killing of cancer cells in deep tissues, the material is non-toxic to normal cells, has good biocompatibility and non-invasive therapeutic effect, and significantly improves treatment efficiency.

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Abstract

The application discloses a cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial and a preparation method thereof. First, mesoporous cobalt ferrite is obtained through a hydrothermal method, then platinum is in-situ grown on the surface of the mesoporous cobalt ferrite, and finally polyethylene glycol is coated on the surface of the cobalt ferrite@platinum through hydrogen bond action to obtain the composite anticancer nanomaterial. Researches show that the composite anticancer nanomaterial synthesized by the application can kill cancer cells specifically and efficiently through the synergistic effect of chemical kinetics therapy and sonodynamic therapy, and has no toxic effect on normal cells.
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Description

Technical Field

[0001] This invention relates to the technical fields of nanotechnology and biomedical materials, and in particular to a cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial and its preparation method. Background Technology

[0002] Chemotherapy, radiotherapy, and surgery are traditional methods for treating cancer. Despite continuous improvements, these methods still have some limitations. Chemotherapy and radiotherapy can effectively kill cancer cells to a certain extent. However, during long-term chemotherapy and radiotherapy, cancer cells develop resistance, reducing the effectiveness of the treatment. Surgical resection is difficult to completely eliminate cancer cells and is ineffective against metastases. Therefore, finding effective, safe, and inexpensive treatment methods has become crucial. Based on this, new non-invasive methods for treating malignant tumors have emerged, including photothermal therapy, photodynamic therapy, acoustic therapy, and chemodynamic therapy.

[0003] Among these novel methods, photothermal therapy utilizes the photothermal conversion properties of materials to transform absorbed light energy into heat energy, thereby killing and eliminating tumor cells. Chemokinetic therapy (CDT) is highly specific and requires no additional energy input. The Fenton reaction is the basis of chemokinetic therapy; the ·OH generated by this reaction can kill tumor cells. However, both photothermal and chemokinetic therapies have drawbacks. The penetration depth of light is limited, making it difficult for photothermal materials to exert their effects at deeper levels; the Fenton reaction is pH-sensitive, producing only a small amount of ·OH at high pH, ​​making it difficult to clear tumors in deep tissues, as illustrated by Chinese patent (publication number: CN 114261993A) on cobalt ferrite nanoparticles and their preparation method and application. Sonodynamic therapy (SDT) can effectively address this problem. Sonodynamic therapy has minimal invasiveness and maximum tissue penetration depth, generating ROS-activated cell death signaling pathways under ultrasound-triggered sonosensitization. The sonosensitizer can rapidly generate active electrons (e) from the band structure. - ) / hole(h + Yes, and subsequently converts the surrounding H2O2 / O2 into cytotoxic ROS. Simultaneously, the Fenton reaction reagent possesses catalase properties, capable of generating both ROS and O2. Modifying its surface with platinum nanoparticles further enhances catalytic efficiency and improves the efficacy of sonodynamic therapy. When CDT is used in combination with SDT, it can compensate for the hypoxia in the tumor microenvironment and enhance the effect of the sonosensitive agent. Based on this, this invention combines chemical kinetics with sonodynamic therapy, generating reactive oxygen species and catalyzing H2O2 in the tumor microenvironment to provide O2 for sonodynamic therapy, achieving a synergistic anti-tumor effect. Summary of the Invention

[0004] This invention addresses the problems of low reactive oxygen species generation efficiency and insufficient anticancer activity of single materials by proposing a cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial and its preparation method, aiming to provide an anticancer material with high reactive oxygen species production and strong killing effect on cancer cells.

[0005] To achieve the above objectives, the technical solution provided by this invention is: a method for preparing cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterials, comprising the following steps:

[0006] 1) Mesoporous cobalt ferrite was obtained by hydrothermal method, and then dried after repeated washing with water or ethanol;

[0007] 2) Disperse the dried material obtained in step 1) in water, add polyvinylpyrrolidone and chloroplatinic acid, stir the reaction in a water bath, centrifuge and wash repeatedly with deionized water and acetone to obtain cobalt ferrite@platinum;

[0008] 3) Disperse the cobalt ferrite@platinum obtained in step 2) in water, add polyethylene glycol, stir, centrifuge, wash away excess polyethylene glycol with deionized water, and freeze-dry to obtain the desired cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial.

[0009] Further, in step 1), the molar ratio of cobalt to iron added in the hydrothermal synthesis is 1:1 to 1:2; the template agent added in the hydrothermal synthesis is a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer, also called P123, with a molar ratio of 1:1 to 1:2 to the total of iron and cobalt salts; the complexing agent added in the hydrothermal synthesis is anhydrous sodium acetate, with a molar ratio of 2:1 to 3:1 to the total of iron and cobalt salts; the temperature used in the hydrothermal synthesis is 160-200℃; and the time required for the hydrothermal synthesis is 16-24 hours.

[0010] Further, the specific process of step 1) is as follows: add cobalt salt, iron salt, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer and sodium acetate to ethylene glycol and stir to dissolve. Then transfer the dissolved solution to the reaction vessel, adjust the corresponding temperature of the oven to carry out hydrothermal reaction, discard the supernatant after the reaction is completed, and wash the precipitate repeatedly with water or ethanol.

[0011] Further, in step 2), the added polyvinylpyrrolidone uses ethylene glycol as a solvent with a concentration of 20-100 mg / ml; the added chloroplatinic acid uses ethylene glycol as a solvent with a concentration of 8-12 mg / ml; the volume ratio of added polyvinylpyrrolidone to chloroplatinic acid is 1:1; the water bath temperature is 60-100℃; and the water bath time is 1-6 hours.

[0012] Furthermore, the specific process of step 2) is as follows: take the dried material from step 1), add anhydrous methanol, sonicate for 15 minutes, add polyvinylpyrrolidone and chloroplatinic acid dropwise and stir for 30 minutes, transfer to a three-necked flask and stir in a water bath, reflux, discard the supernatant after the reaction is completed, and wash repeatedly with water or acetone.

[0013] Further, in step 3), the polyethylene glycol is a 1-10 wt% aqueous solution with a molecular weight of 2000-3000; the cobalt ferrite@platinum is a 1-10 wt% aqueous solution.

[0014] The present invention also provides a cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial prepared by the above method. This cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial can specifically and efficiently kill cancer cells through the synergistic effect of chemokinetic therapy and sonodynamic therapy, without toxicity to normal cells.

[0015] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0016] This invention synthesizes nanomaterials with significantly enhanced sonodynamic therapeutic effects using a simple hydrothermal method. Sonodynamic therapy penetrates deeper into tissues, enabling targeted, non-invasive treatment and improving treatment efficiency.

[0017] Cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterials can specifically respond to the unique weakly acidic environment of tumors. Under acidic pH conditions, the nanoparticles can dissociate with iron, undergoing a Fenton reaction to generate reactive oxygen species for chemodynamic therapy. Simultaneously, the application of ultrasound rapidly generates an active electron (e) from the band structure. - ) / hole(h + Yes, it converts the surrounding H2O / O2 into reactive oxygen species, thereby killing cells. Cobalt ferrite can catalyze the reaction of H2O2 in the tumor microenvironment to produce oxygen, providing raw materials for sonodynamic therapy.

[0018] Grafting polyethylene glycol onto the surface of nanoparticles can effectively reduce cytotoxicity. The glycol units form a tight bond with water molecules, creating a hydration layer. This hydration layer prevents nanoparticle aggregation, hinders protein adsorption and the clearance of polysulfated mucopolysaccharides, thereby extending the lifespan of nanoparticles in vivo.

[0019] This invention has good biocompatibility; when the material concentration is 300 μg / mL, the hemolysis rate is less than 5%, and the cell survival rate still reaches more than 80%.

[0020] This invention is at 1W / cm 2Under ultrasonic intensity, it exhibits superior reactive oxygen species production capability. When ultrasound is applied in a simulated tumor environment, the tumor cell survival rate is 30% when the material concentration is 150 μg / mL, and 20% when the material concentration is 300 μg / mL.

[0021] This invention does not produce side effects on normal cells. Furthermore, by combining chemokinetics with sonodynamic therapy, it achieves a synergistic anti-cancer effect, realizing non-invasive cancer treatment, and possesses significant basic research value and application potential. Attached Figure Description

[0022] Figure 1 This is a transmission electron microscope (TEM) image of the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial prepared in Example 1.

[0023] Figure 2 The image shows the X-ray powder diffraction pattern of the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial prepared in Example 1.

[0024] Figure 3 The graph shows the dissolved oxygen generation catalyzed by the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterials prepared in Example 1 at different concentrations.

[0025] Figure 4 This is a graph showing the ability of the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial prepared in Example 1 to generate ·OH with and without platinum modification.

[0026] Figure 5 The image shows the total reactive oxygen species fluorescence spectrum generated in vitro for the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial prepared in Example 1.

[0027] Figure 6 The UV diffuse reflectance spectrum and UV diffuse reflectance Tauc diagram of the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterials prepared in Example 1 are shown.

[0028] Figure 7 The images show the in vitro and in vivo glutathione consumption effects of the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterials prepared in Example 1.

[0029] Figure 8 The diagram shows the biocompatibility and blood compatibility of the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterials prepared in Example 1.

[0030] Figure 9 The image shows an inverted fluorescence micrograph of the intracellular reactive oxygen species generated in the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterials prepared in Example 1.

[0031] Figure 10 The image shows the anticancer activity of the cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial prepared in Example 1. Detailed Implementation

[0032] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments, but the implementation of the present invention is not limited thereto. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art.

[0033] Example 1

[0034] Step 1: Weigh 3 mmol of P123 and add it to 40 mL of ethylene glycol in a 60 °C water bath. Stir and dissolve the solution, and record this as solution a. Weigh 3 mmol of cobalt chloride hexahydrate and 3 mmol of ferric chloride hexahydrate and add them to solution a. Stir and dissolve the solution in a water bath, and record this as solution b. Weigh 15 mmol of anhydrous sodium acetate and add it to solution b. Stir and dissolve the solution in a water bath for half an hour, and record this as solution c. Transfer solution c to a 100 mL reactor and keep it at 200 °C for 16 hours. Discard the supernatant. Wash the product repeatedly with water and anhydrous ethanol three times. Dry it under vacuum at 60 °C overnight. After grinding, obtain a dark brown mesoporous cobalt ferrite powder, which is called CoFe2O4.

[0035] Step 2: Weigh 0.1g of CoFe2O4 synthesized in Step 1, add 25mL of methanol, sonicate for 15min, slowly add 1mL of 8mg / mL chloroplatinic acid solution (using ethylene glycol as solvent) and 1mL of 90mg / mL polyvinylpyrrolidone solution (using ethylene glycol as solvent) dropwise, stir for 30min, transfer to a three-necked flask, reflux at 80℃ for 3h, cool, wash three times with deionized water / acetone, and finally dry under vacuum at 60℃ to obtain CoFe2O4@Pt;

[0036] Step 3: Weigh 1g of CoFe2O4@Pt synthesized in Step 2 into a beaker, add 100mL of deionized water and sonicate for 30min, which is recorded as solution d. Weigh 3g of polyethylene glycol with a molecular weight of 2000 into a beaker, add 100mL of deionized water, stir to dissolve, and then add solution d. Stir at room temperature for 24h, wash away unreacted polyethylene glycol with deionized water, and freeze-dry to obtain CoFe2O4@Pt-PEG powder, which is cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial.

[0037] Figure 1 The image shows a transmission electron microscope (TEM) image of CoFe2O4@Pt-PEG. It can be seen from the image that the synthesized cobalt ferrite is about 200 nm in size. After doping with platinum, obvious platinum particles can be seen on the surface. The platinum particles are about 2 nm in size and are uniformly distributed.

[0038] Figure 2The image shows the XRD pattern of CoFe2O4@Pt-PEG. From the image, we can see the characteristic peaks of spinel crystals, such as (220), (311), (400), (511) and (440). It can be seen that the synthesized cobalt ferrite is spinel type, with sharp peaks and good crystallinity. The crystallinity is improved after doping with platinum.

[0039] Figure 3 The dissolved oxygen production catalyzed by CoFe2O4@Pt-PEG at different concentrations was measured to verify its ability as a catalase. When the CFP concentration reached 100 μg / mL, the soluble O2 showed an increasing trend within 10 min, demonstrating effective enzymatic decomposition of H2O2.

[0040] Figure 4 This study aimed to verify the ROS production capacity of CoFe2O4 materials with and without Pt surface modification. Since ·OH is the most potent ROS known to kill cancer cells, the ability of the material to produce ·OH was first verified. Because ·OH reacts with 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue color, TMB was used as an indicator to verify ·OH production. The results show that Pt surface modification enhances the material's ROS production capacity.

[0041] Figure 5 This study validated the ability of CoFe2O4@Pt-PEG to generate ROS at different concentrations. Using 2',7'-dichlorofluorescein (DCFH) as a probe, a characteristic peak was observed at 525 nm under 488 nm excitation when reactive oxygen species (ROS) were generated. A larger peak at 525 nm indicates more ROS generation. The fluorescence intensity increased with increasing material concentration, indicating more ROS generation. These results demonstrate that the composite material of this invention can generate ROS, and this generation increases with increasing concentration.

[0042] Figure 6 The images show the UV diffuse reflectance spectrum and UV diffuse reflectance Tacu plot of CoFe2O4@Pt-PEG. It can be seen that the material exhibits a continuous absorption band in the 200-950 nm visible light range. Based on the UV diffuse reflectance Tacu plot, the band gap of the material is calculated to be 1.18 eV, which is much lower than most inorganic sonic sensitizers. Applying ultrasound to the material can drive the separation of electron-hole pairs more quickly, thereby enhancing the SDT effect.

[0043] Figure 7 The figures show the in vitro and in vivo glutathione consumption effects of CoFe2O4@Pt-PEG. As can be seen from the figures, the in vitro glutathione consumption of the material increases with the increase of the material concentration. Compared with the blank group, the intracellular glutathione level of the material-treated cells is significantly reduced.

[0044] Figure 8The figure shows the blood compatibility and biocompatibility of CoFe2O4@Pt-PEG at different concentrations. As can be seen from the figure, when the material concentration is 300 μg / mL, the blood compatibility is below 5% and the cell viability is above 80%, indicating that it has excellent blood compatibility and biocompatibility.

[0045] Figure 9 This is an inverted fluorescence micrograph of intracellular reactive oxygen species (ROS). The probe DCFH-DA itself is non-fluorescent and can freely cross the cell membrane. After entering the cell, it can be hydrolyzed by intracellular esterases to generate DCFH. Intracellular ROS can oxidize the non-fluorescent DCFH to generate fluorescent DCF. The presence of green fluorescence in the image indicates the presence of ROS. The addition of hydrogen peroxide and the application of sonication resulted in more green fluorescence, indicating that the combination of chemical kinetics and acoustic kinetics can generate more ROS.

[0046] Figure 10 The figure shows the tumor-killing effect of different concentrations of CoFe2O4@Pt-PEG under different conditions. As can be seen from the figure, the cell survival rate decreases with the increase of material concentration. The survival rate is even lower when hydrogen peroxide or ultrasound is added than when the material is added alone. The survival rate of the group with hydrogen peroxide and ultrasound is the lowest among the four groups, indicating that chemokinetics and sonodynamic therapy have a synergistic effect and can enhance the killing ability of cancer cells.

[0047] Example 2

[0048] Unlike Example 1, in step 1), 2.57 mmol of cobalt chloride hexahydrate and 3.43 mmol of ferric chloride hexahydrate were weighed and added to solution a and stirred in a water bath until dissolved.

[0049] Example 3

[0050] Unlike Example 1, in step 1), 2.25 mmol of cobalt chloride hexahydrate and 3.75 mmol of ferric chloride hexahydrate were weighed and added to solution a and stirred in a water bath until dissolved.

[0051] Example 4

[0052] Unlike Example 1, in step 1), 2 mmol of cobalt chloride hexahydrate and 4 mmol of ferric chloride hexahydrate are weighed and added to solution a and stirred in a water bath until dissolved.

[0053] Example 5

[0054] Unlike Example 1, in step 1), 6 mmol of P123 was weighed and added to 40 mL of ethylene glycol, which was then stirred and dissolved in a 60°C water bath. The solution was then transferred to a 100 mL reaction vessel and kept at 160°C for 16 hours.

[0055] Example 6

[0056] Unlike Example 1, in step 1), 12 mmol of anhydrous sodium acetate was weighed and added to solution b, which was stirred in a water bath for half an hour.

[0057] Example 7

[0058] Unlike Example 1, in step 1), 18 mmol of anhydrous sodium acetate was weighed and added to solution b, which was stirred in a water bath for half an hour.

[0059] Example 8

[0060] Unlike Example 1, the concentration of the polyvinylpyrrolidone / ethylene glycol solution in step 2) is 20 mg / ml.

[0061] Example 9

[0062] Unlike Example 1, the concentration of the polyvinylpyrrolidone solution in step 2) is 100 mg / ml, and the concentration of the chloroplatinic acid solution is 12 mg / ml.

[0063] Example 10

[0064] Unlike Example 1, in step 2), the solution is transferred to a three-necked flask and refluxed at 60°C for 6 hours.

[0065] Example 11

[0066] Unlike Example 1, in step 2), the solution is transferred to a three-necked flask and refluxed at 100°C for 1 hour.

[0067] Example 12

[0068] Unlike Example 1, in step 3), 1g of polyethylene glycol with a molecular weight of 3000 is weighed into a beaker and 100mL of deionized water is added.

[0069] Example 13

[0070] Unlike Example 1, in step 3), 10g of CoFe2O4@Pt synthesized in step 2 was weighed into a beaker, 100mL of deionized water was added, and the mixture was sonicated for 30min; 10g of polyethylene glycol with a molecular weight of 3000 was weighed into a beaker, and 100mL of deionized water was added.

[0071] Comparative Example 1

[0072] Step 1: Dissolve 0.36 g of ferric chloride hexahydrate and 0.19 g of cobalt chloride hexahydrate in 20 mL of ethylene glycol, then add 0.9 g of sodium acetate. Add sodium hydroxide dropwise to the original system until the pH reaches 12. Transfer the mixture to a tetrafluoroethylene container, which is then sealed in a stainless steel autoclave. Heat at a rate of 2 °C / min and maintain at 200 °C for 6 h. Discard the supernatant, and wash the product three times repeatedly with water and anhydrous ethanol.

[0073] Step 2: Reconcile the product from Step 1 with NH2-PEG 3400 -COOH was mixed in equal mass with 50 ml of deionized water and stirred at 25 °C for 24 h. Finally, the product was magnetically separated and washed three times with deionized water.

[0074] Comparative Example 2

[0075] Step 1: Dissolve 100 mg of methoxy polyethylene glycol polylactic acid in 2 ml of deionized water to prepare a stabilizer solution. Then, dissolve 0.2 mmol of ferric chloride hexahydrate and 0.1 mmol of cobalt chloride hydrate in 23 mL of ethylene glycol solution, mix well, and add the stabilizer solution and 0.5 g of anhydrous sodium acetate sequentially while stirring. Stir at 600 rpm for 60 min, transfer to a reaction vessel, and react at 200 °C for 24 h. After the reaction is complete, dialyze with a mixture of deionized water and ethanol, and freeze-dry to obtain the product.

[0076] The ROS production performance of the composite materials obtained in the above examples and comparative examples was tested. The sample concentration was uniformly 300 μg / mL, the solvent was deionized water, the H2O2 concentration was 100 μm, and 2',7'-dichlorofluorescein (also known as DCFH) was used as the probe at a concentration of 10 μm. After preparing a 1 mL solution, the mixture was shaken on a shaker for 20 min. The experimental materials were then sonicated for 3 min using a Wilder ultrasound therapy instrument at an ultrasonic intensity of 1 W / cm2. After centrifugation for 5 min, 200 μL of the supernatant was collected into a 96-well plate, and the fluorescence intensity at 525 nm was measured under 525 nm excitation light using a microplate reader.

[0077] When reactive oxygen species (ROS) are generated, DCFH can produce a characteristic peak at 525 nm under 488 nm excitation. The larger the peak value at 525 nm, the more ROS are generated.

[0078] The comparative test analysis is shown in Table 1 below.

[0079] Table 1 Comparison of ROS performance tests between the examples and the comparative examples.

[0080] type fluorescence intensity Example 1 3108.29 Example 2 2849.84 Example 3 2625.89 Example 4 2326.26 Example 5 2956.02 Example 7 2831.48 Example 8 2789.65 Example 9 2864.23 Example 10 2836.27 Example 11 2763.66 Example 12 2940.05 Example 13 2917.69 Comparative Example 1 1054.89 Comparative Example 2 529.84

[0081] The examples used four different feed ratios for surface platinum modification, and it can be seen that all of them produced more ROS than the control ratio. This indicates that platinum modification can effectively improve the material's ability to generate ROS after ultrasound, and can enhance the effect of sonodynamic therapy, which is worth promoting.

[0082] The embodiments of the present invention are merely examples for clearly illustrating the invention and are not intended to limit the implementation of the invention. Those skilled in the art will recognize that other variations or modifications can be made based on the above embodiments, and it is neither necessary nor possible to exhaustively describe all possible implementations here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterials, characterized in that, Includes the following steps: 1) Mesoporous cobalt ferrite was obtained by hydrothermal method, and then dried after repeated washing with water or ethanol. The specific process is as follows: Add cobalt salt, iron salt, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer and sodium acetate to ethylene glycol and stir to dissolve. Then transfer the dissolved solution to a reaction vessel, adjust the oven temperature accordingly to carry out hydrothermal reaction, discard the supernatant after the reaction is completed, and wash the precipitate repeatedly with water or ethanol. The hydrothermal synthesis method uses a cobalt-iron molar ratio of 1:1 to 1:

2. The template agent used is a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer, also known as P123, with a molar ratio of 1:1 to 1:2 with the total iron and cobalt salts. The complexing agent used is anhydrous sodium acetate, with a molar ratio of 2:1 to 3:1 with the total iron and cobalt salts. The hydrothermal synthesis method uses a temperature of 160-200℃ and requires 16-24 hours. 2) Disperse the dried material obtained in step 1) in water, and add polyvinylpyrrolidone and chloroplatinic acid to it. Stir the reaction in a water bath, centrifuge, and wash repeatedly with deionized water and acetone to obtain cobalt ferrite@platinum. The specific process is as follows: Take the dried material from step 1), add anhydrous methanol, sonicate for 15 min, add polyvinylpyrrolidone and chloroplatinic acid dropwise and stir for 30 min, transfer to a three-necked flask and stir in a water bath, reflux, discard the supernatant after the reaction is complete, and wash repeatedly with water or acetone. The added polyvinylpyrrolidone uses ethylene glycol as a solvent at a concentration of 20-100 mg / ml; the added chloroplatinic acid uses ethylene glycol as a solvent at a concentration of 8-12 mg / ml; the volume ratio of added polyvinylpyrrolidone to chloroplatinic acid is 1:1; the water bath temperature is 60-100℃; the water bath time is 1-6 hours. 3) Disperse the cobalt ferrite@platinum obtained in step 2) in water, add polyethylene glycol, stir, centrifuge, wash away excess polyethylene glycol with deionized water, and freeze-dry to obtain the desired cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial. This cobalt ferrite@platinum polyethylene glycol composite anticancer nanomaterial can specifically and efficiently kill cancer cells through the synergistic effect of chemokinetic therapy and sonodynamic therapy, without toxicity to normal cells; wherein, the polyethylene glycol is a 1-10 wt% aqueous solution with a molecular weight of 2000-3000; the cobalt ferrite@platinum is a 1-10 wt% aqueous solution.

Citation Information

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