Palladium-loaded carbon-based tungsten oxide nano composite material as well as preparation method and application thereof
By preparing palladium-loaded carbon-based tungsten oxide nanocomposite material Pd/WO2.90@C, the targeting and biosafety issues of existing platinum-based nanocatalysts in tumor treatment are solved, achieving efficient and safe tumor treatment effects, and is suitable for a variety of tumor treatments and free radical reactions.
Patent Information
- Application Number
- CN202510885926.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-30
- Publication Date
- 2025-09-26
AI Technical Summary
Existing platinum-based nanocatalysts have low targeting effects and efficiency in the treatment of tumors such as ovarian cancer, malignant lymphoma, and breast cancer, leading to strong cytotoxic side reactions. In addition, traditional preparation methods make it difficult to control the morphology, size, and degree of reduction, resulting in poor biosafety.
A palladium-loaded carbon-based tungsten oxide nanocomposite material Pd/WO2.90@C was prepared by a green calcination-reduction method. Through the mesoporous structure and uniform dispersion of palladium, combined with DSPE-PEG-NH2 coating, it achieved high catalytic activity and biocompatibility and is suitable for intravenous or intratumoral injection.
It achieves efficient and safe tumor treatment effects, significantly inhibits the proliferation of breast cancer cells through the synergistic effect of multiple free radicals, and solves the biosafety and preparation problems of traditional methods. It is suitable for a variety of tumor treatments and free radical reactions.
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Figure CN120695031A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of nanomaterial preparation, and in particular to a palladium-loaded carbon-based tungsten oxide nanocomposite material, a preparation method thereof, and applications thereof. Background Art
[0002] At present, cisplatin, a commonly used chemotherapy drug in clinical practice, has certain therapeutic effects on ovarian cancer, malignant lymphoma, breast cancer, etc. It is a platinum metal complex, and its main target is DNA. It acts on the cross-links between and within DNA chains to form DNA complexes, interfere with DNA replication, transcription, and repair, causing cell cycle arrest, or binds to nuclear proteins and cytoplasmic proteins to cause cytotoxicity. Other platinum-based drugs such as carboplatin and oxaliplatin also have high anti-tumor activity, but their administration method is generally intravenous injection, reaching the tumor site with the blood, and their targeting effect and efficiency are relatively low. They have strong cytotoxicity after being taken up by normal cells, and severe side effects such as vomiting and pain are prone to occur after cell damage.
[0003] In contrast, palladium and platinum are both in Group VIII of the periodic table, each containing 10 electrons in its outermost atomic orbitals. They have similar chemical properties, and palladium is less biotoxic than platinum. The lethal oral doses of palladium and platinum in rats are greater than 9100 mg / kg and 129 μg / kg, respectively. Therefore, palladium-based nanocatalysts are expected to exhibit superior biosafety compared to platinum-based nanocatalysts.
[0004] In recent reports, the preparation of platinum-group nanocatalysts for biological and catalytic reactions has primarily been achieved through hydrothermal and strong reducing agent methods. Although the resulting materials exhibit high crystallinity, the synthesis process is difficult to replicate, and the morphology, size, and degree of reduction are challenging to control. The large size of the catalysts can lead to poor biosafety, causing vascular occlusion and liver accumulation, resulting in poor in vivo metabolism. Furthermore, the active sites are less exposed. Therefore, the development of green, efficient, simple, easily reproducible, and mass-producible nanocatalysts with targeted properties and reduced biotoxicity is urgently needed.
[0005] Correspondingly, palladium is the most easily oxidized and active metal among the platinum group metals. Under the same conditions, palladium is more likely to lose electrons than platinum and be oxidized to palladium oxide. In order to maintain the electron-rich characteristics of metallic palladium, WO with rich oxygen vacancies was specifically introduced. 2.90 , can effectively regulate the electronic structure of the catalyst surface, enhance electron enrichment, activate H2O2, and promote the generation of ·OH. On the other hand, it also improves the charge transfer ability of the material, which is more conducive to the redox process of gaining and losing electrons. At the same time, it has been reported that WO X The biological toxicity is low, which can ensure the safety and effectiveness of the treatment process.
[0006] In view of the above arguments, the present invention has developed a green, efficient, and mass-producible palladium-based nanocatalyst and explored its application in the treatment of ferroptosis in breast cancer. Summary of the Invention
[0007] In order to solve the deficiencies in the prior art, the first aspect of the present invention provides a method for preparing a palladium-loaded carbon-based tungsten oxide nanocomposite material, comprising the following steps:
[0008] Step (1): WO 2.90 Preparation of C precursor
[0009] Mix carbon black and tungsten salt, add deionized water and isopropanol, adjust the pH to 1-8, ball mill, and centrifuge to obtain WO 2.90 / C precursor;
[0010] Step (2): Sintering
[0011] The WO obtained in step (1) 2.90 The / C precursor was heat treated in a nitrogen atmosphere to obtain WO 2.90 / C matrix;
[0012] Step (3): Palladium loading
[0013] The palladium salt is dispersed in ethanol to obtain a palladium salt ethanol solution, and the palladium salt ethanol solution is mixed with WO 2.90 / C matrix, stirred and evaporated, dried and then heat treated in 1-10% argon-hydrogen mixed gas to obtain Pd / WO 2.90 @C nanocomposite material, 1-10% argon-hydrogen mixture is a mixture of hydrogen with a mass fraction of 1-10% and the remainder being argon.
[0014] Furthermore, in step (1), the carbon black is selected from one of graphite, acetylene black, and VXC72R conductive carbon black;
[0015] Furthermore, the tungsten salt is selected from one of sodium tungstate, ammonium metatungstate, phosphotungstic acid, and tungstic acid;
[0016] Furthermore, the mass ratio of the carbon black and the tungsten salt is 1:2-1:5, and the volume ratio of the deionized water and isopropyl alcohol is 2:1-5:1;
[0017] Furthermore, the ball milling time is 2-12 hours, and the ball milling speed is 200-600 rpm.
[0018] Furthermore, in step (2), the heat treatment conditions are to increase the temperature to 400-600°C at a heating rate of 5-10°C / min and keep the temperature for 1-9h.
[0019] Furthermore, in step (3), the palladium salt is selected from one of palladium chloride, palladium nitrate, palladium sulfate, and palladium acetate;
[0020] Furthermore, in step (3), the heat treatment conditions are to increase the temperature to 100-800°C at 1-20°C / min and keep the temperature for 1-8h;
[0021] Furthermore, the stirring evaporation is carried out at 50-80° C. and the stirring speed is 200-600 rpm.
[0022] The second aspect of the present invention provides Pd / WO prepared by any of the above methods 2.90 @C nanocomposite material, the material has a mesoporous structure, and the pore size of the mesoporous structure is 2-10nm.
[0023] Furthermore, palladium is represented by Pd 0 valence states exist, the palladium mass fraction is 0-50wt%, and the carbon mass fraction is 50-80wt%;
[0024] Furthermore, the palladium loading is 0-30 wt%, preferably 1-6 wt%; the palladium nanoparticles have a particle size of 1-10 nm and are uniformly dispersed.
[0025] Furthermore, the Pd / WO 2.90 @C nanocomposite material consists of palladium particles with an average particle size of 1-10nm, WO particles with an average particle size of 50-100nm 2.90 Particles and 50nm carbon-based carrier.
[0026] The third aspect of the present invention provides the Pd / WO 2.90 @CApplication of nanocomposites in the preparation of drugs for the treatment of breast cancer.
[0027] Furthermore, the Pd / WO 2.90 The @C nanocomposite material was coated with DSPE-PEG-NH2 by the following method: 2.90 @C Nanocomposite materials were dispersed in DMF, and DSPE-PEG-NH2 DMF solution was added. After reaction for 12 h, centrifugation and washing were performed.
[0028] Furthermore, the drug is administered via intravenous or intratumoral injection, utilizing its catalytic activity to generate hydroxyl radicals and carbon free radicals, thereby inhibiting the proliferation of 4T1 tumor cells.
[0029] Compared with the prior art, the present invention has the following advantages:
[0030] 1. The present invention adopts the strategy of calcination reduction synthesis and takes advantage of the high biocompatibility of DSPE-PEG-NH2 to batch synthesize a Pd / WO with ultra-small size, excellent structural stability, excellent biocompatibility and renal metabolism. 2.90 @C nanocatalyst. Compared with traditional hydrothermal and strong reducing material reduction methods, this preparation method is greener, more efficient, simpler, easier to repeat, and can be mass-produced. The prepared material has a size of about 50nm and is covered with a surface modification material with excellent biocompatibility, which can greatly enhance its dispersibility and produce free radical responses in a timely and specific manner.
[0031] 2. Pd / WO prepared by the present invention 2.90 @C nanocatalyst can achieve ferroptosis-like treatment for breast cancer, which has good breast cancer treatment effect and safety. This therapy is a kind of multiple free radicals ( 1 This study explores the synergistic effects of O2, ·OH, and ·C on tumors. By leveraging their favorable tumor microenvironmental response to generate diverse and abundant reactive free radicals, they aim to achieve ferroptosis-like breast cancer treatment using non-iron-based catalysts and investigate their mechanism of action. However, this approach is not targeted at treating only one type of tumor; it could be applied to tumors with similar intracellular microenvironments. It should be noted that this synthetic approach can be extended to the design of other nanocatalysts and applied to tumor treatment and other reactions involving free radical catalysis.
[0032] 3. The preparation method of the present invention addresses the bottleneck problem that has long plagued the mass production of nanoscale palladium and oxygen-vacancy-rich tungsten oxide in the field. The calcination-reduction preparation strategy proposed in the present invention is simple, efficient, easily scalable, and environmentally friendly. This nanocatalyst has a wide range of applications, strong scalability, and excellent biocompatibility, addressing the toxicity, poor efficacy, and poor prognosis of platinum-based chemotherapy drugs.
[0033] 4. This invention addresses the problem of insufficient research on the mechanism of ferroptosis-like reactions in existing studies. By deeply studying the mechanism of free radical production stimulated by the tumor intracellular microenvironment, it can be expanded to other tumor treatments and free radical reaction research. BRIEF DESCRIPTION OF THE DRAWINGS
[0034] Figure 1 A: Pd / WO 2.90 @C TEM characterization of nanocatalysts and their ability to undergo Tyndall effect in aqueous solution;
[0035] Figure 1 B: H&E staining results of the heart, liver, spleen, lung, and kidney of ICR mice on day 28 after administration.
[0036] Figure 1 C: 4T1 tumor growth curve.
[0037] Figure 1 D:Pd / WO 2.90 @C、Pd@C、WO 2.90 @C and C's XRD results.
[0038] Figure 1 E:Pd / WO 2.90 @C and other comparison samples added DMPO capture agent ESR test results.
[0039] Figure 1 F:Pd / WO 2.90 @C and other comparison samples with TEMP capture agent added to ESR test results. DETAILED DESCRIPTION
[0040] The present invention is described in detail below with reference to specific embodiments.
[0041] The present invention will be described in detail below with reference to specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those skilled in the art, several variations and improvements can be made without departing from the scope of the present invention. These all fall within the scope of protection of the present invention.
[0042] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.
[0043] Unless otherwise specified, the experimental materials and reagents used in the following examples were obtained from commercial sources.
[0044] The embodiments of the present invention will be described in detail below with reference to the examples, but it will be understood by those skilled in the art that the following examples are merely illustrative of the present invention and should not be construed as limiting the scope of the invention. Where specific conditions are not specified in the examples, the methods are carried out according to conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, all reagents or instruments used can be commercially available.
[0045] Example 1: Pd / WO 2.90 @C Preparation of nanomedicine
[0046] Step (1): WO 2.90 Preparation of C precursor
[0047] Mix 1 g of carbon black with 2 g of tungstic acid, add 20 mL of deionized water and 10 mL of isopropanol, ball mill for 6 h (400 rpm), centrifuge and dry at room temperature.
[0048] Step (2): Sintering
[0049] Under nitrogen, the temperature was raised to 400℃ at 2℃ / min and kept for 1h to obtain WO 2.90 / C porous support.
[0050] Step (3): Palladium loading
[0051] Take 0.05g palladium nitrate and dissolve it in 50mL ethanol, add 1g WO 2.90 / C, stirred at 50°C (400 rpm) until the solvent was evaporated to dryness, and treated at 400°C for 1 h in a 2% argon-hydrogen mixture (heating rate of 3°C / min).
[0052] Comparative Example 1:
[0053] Pd@C、WO 2.90 @C and C are comparative examples. The preparation process and conditions are the same as those of Pd / WO in Example 1. 2.90 @C, but the W source, Pd source and W / Pd source are missing respectively.
[0054] Example 2: Material Characterization
[0055] 1. TEM analysis
[0056] The Pd / WO prepared in Example 1 2.90 @C nanocomposites were characterized by transmission electron microscopy. Figure 1 A is the Pd / WO prepared in Example 1 2.90 TEM characterization of @C nanocatalyst and its ability to undergo Tyndall effect in aqueous solution.
[0057] TEM was performed using a FEI TECNAI F20 electron microscope (200 kV) to confirm that Pd / WO 2.90 @C is 5nm Pd and 20nm WO loaded on 50nm carbon spheres 2.90 Compound. Figure 1 TEM of A shows that WO 2.90 Nanoparticles (50-100 nm) are uniformly loaded on the surface of carbon black, and the average particle size of Pd particles is 5 nm.
[0058] 2. XRD analysis: WO 2.90 Characteristic peaks and Pd(111) crystal plane peaks ( Figure 1 D).
[0059] Figure 1 D is Pd / WO 2.90 @C (Example 1), Pd@C, WO 2.90 @ XRD results of C and C (Comparative Example 1). The test instrument is Ultima IV X-ray diffractometer (test parameters: Cu-Kα, 40mA, 40kV). Through this test, it was determined that the materials were Pd / WO 2.90 @C、Pd@C、WO 2.90 @C and C.
[0060] 3. ESR test
[0061] Figure 1 E is the Pd / WO prepared in Example 1 2.90 @C nanocomposite materials and other comparison samples were added with DMPO capture agent ESR test results, from Figure 1 The spectra of E and F show that Pd / WO 2.90 / C can produce hydroxyl radicals, carbon radicals, singlet oxygen, etc.
[0062] Test method: 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) can form a DMPO-OH complex with ·OH. Therefore, DMPO is a universal reagent for capturing ·OH. DMPO (5 μL) was added to a solution (900 μL) containing H2O2 (10 mM), and then 100 μL of drug (250 μg mL) was added. -1 After rotating for 5 minutes, the solution was transferred to a quartz tube for ESR measurement. The results showed that PWC and H2O2 showed better performance than Pd / C (PC) and WO at pH 6.0. 2.9 / C(WC) has the ability to generate ·OH and ·C free radicals, and is better than the ability to generate free radicals under pH 7.4 conditions.
[0063] Figure 1 F is the Pd / WO prepared in Example 1 2.90 @C ESR test results of nanocomposites and other comparison samples with TEMP scavengers added.
[0064] Test method: Tetramethylpiperidinyloxy (TEMP) is a spin trapping agent used to capture and stabilize short-lived free radicals (such as 1 O2, NO, nitric oxide, O2 - ) for detection by electron paramagnetic resonance. TEMP (5 μL) was added to a solution (900 μL) containing H2O2 (10 mM), followed by the addition of 100 μL of drug (250 μg mL -1 After rotating for 5 minutes, the solution was transferred to a quartz tube for ESR measurement. The results showed that PWC reacted with H2O2 to produce 1 The ability of O2 is better than pH 7.4, and PC, WC, and C all have the ability to produce 1 O2's capabilities.
[0065] Example 3: In vivo safety effect evaluation
[0066] The Pd / WO prepared in Example 1 2.90 @C nanocomposite material coated with DSPE-PEG 2000 -NH2 (purchased from Biyuntian), the specific method is to take 20 mg of PdWO 2.90 / C, dissolved in 30mL of DMF, placed in a single-necked flask, and stirred rapidly. Separately, 40mg of DSPE-PEG-NH2 was weighed, dissolved in 5mL of DMF, and added dropwise to the flask containing PdWO 2.90 The reaction was carried out in a 1:1 / C solution for 12 hours, followed by centrifugation and washing, and then dissolved in deionized water to form PWCP. The product was then administered intravenously or intratumorally, utilizing its catalytic activity to generate hydroxyl and carbon radicals, inhibiting the proliferation of 4T1 tumor cells.
[0067] Establishment of mouse model: PdWO was administered to ICR mice via tail vein at 5, 10, or 20 mg / kg. 2.90 / C, were randomly divided into a control group (blank group (normal saline) and an experimental group, and the H&E staining results were obtained.
[0068] like Figure 1 B shows the results of H&E staining of the heart, liver, spleen, lung, and kidney of ICR mice on day 28 after administration. -1 , 10mg kg -1 , 20mg kg -1 There were no obvious abnormalities in the heart, liver, spleen, lung and kidney of mice treated with the dose of .
[0069] Example 4: In vivo therapeutic effects
[0070] Construction of mouse model: BALB / c mice were subcutaneously inoculated with 4T1 tumors and randomly divided into control group (normal saline) and treatment group (PdWO 2.90 / C intravenous injection, 5mg / kg), from Figure 1 C shows that the tumor inhibition rate of the tail vein injection group reached over 80%, and the effect of in situ injection was even better. This nanomedicine has a significant tumor treatment effect.
[0071] Figure 1 C is the 4T1 tumor growth curve. It can be seen that the tumor volume of the PBS (iv, tail vein injection) and PBS (it, intratumoral injection) groups increased significantly, while the 5 mg kg -1 PWCP (iv, tail vein injection), 5 mg kg - 1After 15 days of treatment, the tumor volume of mice in the PWCP (it, intratumoral injection) group was significantly suppressed, with the inhibition rate reaching more than 80%.
[0072] In summary, the Pd / WO prepared by the present invention 2.90 @C is 5nm Pd and 20nm WO loaded on 50nm carbon spheres 2.90 The complex has good breast cancer treatment effect and safety. This therapy is a kind of multiple free radicals ( 1 O2, ·OH and ·C) synergistic tumor treatment.
[0073] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art may make various variations or modifications within the scope of the claims, which do not affect the essence of the present invention.
Claims
1. A method for preparing a palladium-loaded carbon-based tungsten oxide nanocomposite material, characterized in that: The following steps are involved: Step (1): WO 2.90 Preparation of C precursor Mix carbon black and tungsten salt, add deionized water and isopropanol, adjust the pH to 1-8, ball mill, and centrifuge to obtain WO 2.90 / C precursor; Step (2): Sintering The WO obtained in step (1) 2.90 The / C precursor was heat treated in a nitrogen atmosphere to obtain WO 2.90 / C matrix; Step (3): Palladium loading The palladium salt is dispersed in ethanol to obtain a palladium salt ethanol solution, and the palladium salt ethanol solution is mixed with WO 2.90 / C matrix, stirred and evaporated, dried and then heat treated in 1-10% argon-hydrogen mixed gas to obtain Pd / WO 2.90 @C nanocomposite materials.
2. The method for preparing the palladium-loaded carbon-based tungsten oxide nanocomposite material according to claim 1, wherein: In step (1), the carbon black includes one of graphite, acetylene black, and VXC72R conductive carbon black; The tungsten salt is selected from one of sodium tungstate, ammonium metatungstate, phosphotungstic acid, and tungstic acid; The mass ratio of the carbon black and the tungsten salt is 1:2-1:5, and the volume ratio of the deionized water and isopropyl alcohol is 2:1-5:1; The ball milling time is 2-12 hours, and the ball milling speed is 200-600 rpm.
3. The method for preparing the palladium-loaded carbon-based tungsten oxide nanocomposite material according to claim 1, wherein: In step (2), the heat treatment conditions are to increase the temperature to 400-600°C at a heating rate of 5-10°C / min and keep the temperature for 1-9h.
4. The method for preparing the palladium-loaded carbon-based tungsten oxide nanocomposite material according to claim 1, wherein: In step (3), the palladium salt is selected from one of palladium chloride, palladium nitrate, palladium sulfate, and palladium acetate; The heat treatment conditions are to increase the temperature to 100-800°C at 1-20°C / min and keep the temperature for 1-8h; The stirring evaporation is carried out at 50-80° C., and the stirring speed is 200-600 rpm.
5. A Pd / WO prepared by any method of claims 1-4 2.90 @C nanocomposite material, characterized in that The material has a mesoporous structure with a pore size of 2-10 nm; palladium is Pd 0 The valence state exists, the mass fraction of palladium is 0-50wt%, the mass fraction of carbon is 50-80wt%; and the palladium loading is 0-30wt%.
6. The Pd / WO2.90@C nanocomposite material according to claim 5, characterized in that The palladium loading is 1-6 wt %; the particle size of the palladium nanoparticles is 1-10 nm and is uniformly dispersed.
7. Pd / WO according to claim 5 2.90 @C nanocomposite material, characterized in that The Pd / WO 2.90 @C nanocomposite material consists of palladium particles with an average particle size of 1-10nm, WO particles with an average particle size of 50-100nm 2.90 Particles and 50nm carbon-based carrier.
8. A Pd / WO according to any one of claims 5 to 7 2.90 @CApplication of nanocomposites in the preparation of drugs for the treatment of breast cancer.
9. The use according to claim 8, characterized in that The Pd / WO 2.90 The @C nanocomposite material was coated with DSPE-PEG-NH2 by the following method: 2.90 @C Nanocomposite materials were dispersed in DMF, and DSPE-PEG-NH2 DMF solution was added. After reaction for 12 h, centrifugation and washing were performed.
10. The use according to claim 9, characterized in that It is administered by intravenous injection or intratumoral injection, and its catalytic activity is used to produce hydroxyl free radicals and carbon free radicals to inhibit the proliferation of 4T1 tumor cells.