CN114767711B - Redox nano-enzyme for tumor treatment and preparation method thereof - Google Patents
Redox nano-enzyme for tumor treatment and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a redox nano-enzyme for tumor treatment and a preparation method thereof. The invention utilizes a defect engineering strategy to develop simple and effective oxidation-reduction nano enzyme by constructing enzyme simulated active centers, and replaces part of tungsten oxide with iron to form iron-tungsten oxide, which can activate structure reconstruction and generate a large number of defect sites including iron substitution and oxygen vacancy defects, thus remarkably improving binding capacity and catalytic activity. The designed Fe-W oxide nano enzyme can simulate the cascade reaction of catalase and redox active enzyme, induce the substantial damage of redox and metabolic steady state of tumor area, thereby remarkably enhancing the tumor treatment effect. The invention provides a new method for developing the oxidation-reduction nano enzyme for treating tumors.
Description
Technical Field
The invention belongs to the field of nano material preparation and biomedicine, and in particular relates to a redox nano enzyme for tumor treatment and a preparation method thereof
Background
More and more attention is focused on nanoenzyme engineering nanomaterials with enzyme mimetic properties, as they can provide a new platform for developing more advanced tumor-specific therapeutic strategies in biological systems, in particular metallic nanoezymes comprising redox activity, called redox nanoezymes. The inherent redox properties are highly touted by their ability to trigger catalytic reactions in situ and break down the relatively fragile tumor homeostasis. However, developing redox nanoenzymes for cancer treatment, particularly those similar to the native enzymes, remains a significant challenge.
The lack of catalytic active centers is the biggest obstacle faced by redox nanoenzymes. The current research is mainly to introduce catalytically active bio-macromolecular peptides, aptamers, antibodies, etc. into the nano-enzyme frameworks to give them substrate binding functions, or to manipulate the atomic configuration of the metal center and surrounding inside the nano-enzyme, thereby creating basic catalytically active sites. However, the problem is that complex design and synthesis procedures limit their potential. More importantly, these approaches have focused excessively on a single active moiety involved in catalysis, largely ignoring the mechanism of synergy between the different active moieties in the native enzyme. The excellent function and activity achieved by natural enzymes is closely related to the cooperation between internal active sites, and the substrate binding region and catalytic site, two key components of natural enzymes, even though they may be far apart in primary structure, can still form a spatial conformation through peptide chain folding and entanglement, and act together at the active site. Thus, a key step in achieving a true oxidoreductase mimetic is to design the accompanying binding regions and synergistic catalytic sites in a fixed space, while no related nanoenzyme design is currently available.
(one) solving the technical problems
Aiming at the challenges of the prior art, the embodiment of the invention aims to provide a redox nano-enzyme for tumor treatment and a preparation method thereof, and the design strategy of the nano-enzyme reasonably and effectively integrates a key active part, a binding region and a synergistic catalytic site through defect engineering, so that the efficient redox reaction is realized for treating cancers.
(II) technical scheme
In order to achieve the above purpose, the invention mainly adopts the following technical scheme,
the invention firstly discloses a novel oxidation-reduction nano enzyme Fe-WOv developed through defect engineering, which is characterized in that: the nanomaterial body is a tungsten oxide (WOx) nanoparticle in which a portion is replaced with iron to form an iron-tungsten oxide (Fe-WOv) nanoenzyme having oxygen vacancies. The preparation method comprises the following steps:
the first step: tannic Acid (TA), na2WO4.7H2O and FeCl3 were dissolved in 35mL of distilled water; stirring vigorously for 20-60 minutes, and forming a W/Fe-TA complex by self-assembly of metal ions and tannic acid in an aqueous solution based on strong interaction of the metal ions and catechol groups of Tannic Acid (TA);
preferably, the mass of TA added is 0.6g
Preferably, the mass of the added Na2WO4 is 0.43g
Preferably, the mass of FeCl3 added is 0.79g
And a second step of: and transferring the mixed solution into a 50mL polytetrafluoroethylene autoclave, and reacting for 5-20 hours at 120-200 ℃. The Fe-WOv nano structure is synthesized by oxidizing and self-polymerizing an organic ligand in a hydrothermal process and utilizing a metal polyphenol coordination strategy to hydrothermally treat a metal-tannic acid complex; finally, the product was collected and washed 3 times with distilled water.
WOxNPs were obtained by the above synthesis method without the addition of FeCl3.
The invention further discloses application of the novel redox nano enzyme Fe-WOv nano material, which can have binding capacity and catalytic activity at the same time, can simulate cascade reaction of catalase and redox active enzyme, and induces substantial damage of redox and metabolic homeostasis of a tumor area, thereby remarkably enhancing tumor treatment effect.
(III) beneficial technical effects
Compared with the prior art, the invention has the following advantages:
1. the invention develops a novel oxidation-reduction nano enzyme Fe-WOv through defect engineering. Fe doping in WOx (Fe-WOv) can induce a large number of Fe substitutions and Oxygen Vacancy (OV) defects simultaneously, and at the same time, the defective sites are mutually matched and play the binding and catalytic functions observed in most natural enzymes, so that the binding capacity and catalytic activity of Fe-WOv nano-enzymes are remarkably enhanced.
2. The novel redox nano enzyme Fe-WOv prepared by the invention can induce the substantial disruption of redox and metabolic homeostasis in a tumor area through enzyme-like cascade reaction, thereby remarkably improving the tumor treatment effect.
Drawings
FIG. 1 Transmission Electron Microscope (TEM) topography of Fe-WOv nanoenzyme
FIG. 2 particle size distribution diagram of Fe-WOv nanoenzyme
FIG. 3 shows hydrogen peroxide decomposition performance
FIG. 4 graph of glutathione consumption performance
Description of the embodiments
Examples
0.6g TA, 0.43g Na2 WO4.7H2O and 0.79g FeCl3 were dissolved in 35mL distilled water. The mixed solution was transferred to a 50mL polytetrafluoroethylene autoclave with vigorous stirring for 30 minutes and reacted at 160 ℃ for 10 hours. Finally, collecting the product, washing with distilled water for 3 times, and synthesizing to obtain the Fe-WOv nano enzyme. WOxNPs were obtained by the above synthesis method without the addition of FeCl3. The morphology of the Fe-WOv nanoenzyme structure was examined using a Transmission Electron Microscope (TEM) and the result is shown in fig. 1, the Fe-WOv nanoenzyme obtained consisted of rose-like two-dimensional nanoplates with sharp edges, with an average diameter of about 96nm, which is very consistent with the results observed in Dynamic Light Scattering (DLS) in fig. 2.
Examples
The hydrogen peroxide decomposition performance was detected by a titanium sulfate (Ti (SO 4) 2) colorimetric method. After mixing 0.5mL hydrogen peroxide (2.5 mM) and 0.5mL PBS, WOx or Fe-WOv nano enzyme solution for 30 minutes, the mixed solution was added to Ti (SO 4) 2 solution, and 1.33 was mixed to prepare a solution of 24% Ti (SO 4) 2 and 8.33 mL H2SO4 in 50mL distilled water. Ten minutes after the addition of hydrogen peroxide, the concentration of hydrogen peroxide was determined by measuring its absorbance at 405 nm at room temperature. The continuous catalytic effect was verified by repeated addition of 2.5mM hydrogen peroxide to the solution. The residual amount of H2O2 was measured in the same manner as described above. The hydrogen peroxide decomposition performance test results are shown in figure 3, and the results show that the activity of CAT-like enzyme is determined to be very high by the increase of the active oxygen concentration in the H2O2 treatment solution after the Fe-WOv nano enzyme solution is added. In contrast, the activity observed in WOx treatment was negligible.
Examples
Glutathione (GSH) is another important intracellular metabolite that scavenges.oh within tumor cells, enhancing their resistance to oxidative stress. Most metal-based catalysts are rapidly neutralized when exposed to GSH and therefore undoubtedly reduce the therapeutic index. The glutathione consumption was measured by adding DTNB solution (3.0mg.mL-1, 100. Mu.L) and GSH solution (1 mM, 200. Mu.L) to WOx or Fe-WOv nanoenzyme solution (20, 40, 60, 80, 100. Mu.g.mL-1), respectively. The mixture was then kept at 25 ℃ for 30 minutes under magnetic stirring, and the remaining amount of GSH was determined by measuring absorbance at 412 nm. The blank control solution is Fe-WOv nanometer enzyme solution. The consumption detection result of the glutathione is shown in figure 4, and the result shows that the Fe-WOv nano enzyme has good oxidation-reduction activity enzyme-like capacity, can effectively consume GSH, has the GSH conversion rate of 80 percent, is obviously superior to WOx nano enzyme, and can be more efficiently used for tumor treatment.
Claims (4)
1. A redox nanoenzyme for tumor treatment, characterized by: the oxidation-reduction nano enzyme is prepared by dissolving Tannic Acid (TA), na2WO4.7H2O and FeCl3 in distilled water of 35mL, and stirring vigorously for 20-60 minutes, wherein the metal ions and Tannic Acid (TA) catechol groups are based on strong interaction, and the metal ions and the tannic acid self-assemble in an aqueous solution to form a W/Fe-TA complex; and transferring the mixed solution into a 50mL polytetrafluoroethylene autoclave, reacting for 5-20 hours at 120-200 ℃, oxidizing and self-polymerizing the organic ligand in a hydrothermal process, and synthesizing the Fe-WOv nano structure by using a metal polyphenol coordination strategy and hydrothermally treating the metal-tannic acid complex, wherein the redox nano enzyme is mainly tungsten oxide (WOx) nano particles, and part of the redox nano enzyme is replaced by iron to form the iron-tungsten oxide (Fe-WOv) nano enzyme with oxygen vacancies.
2. A method for preparing the oxidoreductase according to claim 1, comprising the steps of: the first step: dissolving Tannic Acid (TA), na2WO4.7H2O and FeCl3 in 35mL of distilled water, and vigorously stirring for 20-60 minutes, wherein the W/Fe-TA complex is formed by self-assembling metal ions and tannic acid in an aqueous solution based on the strong interaction between the metal ions and catechol groups of the Tannic Acid (TA);
and a second step of: transferring the mixed solution into a 50mL polytetrafluoroethylene autoclave, reacting for 5-20 hours at 120-200 ℃, oxidizing and self-polymerizing the organic ligand in the hydrothermal process, synthesizing the Fe-WOv nano structure by using a metal polyphenol coordination strategy and performing hydrothermal treatment on the metal-tannic acid complex, and finally collecting the product and washing with distilled water for 3 times.
3. The preparation method according to claim 2, characterized in that: the mass of Tannic Acid (TA) added was 0.6g, the mass of Na2WO4 was 0.43g, and the mass of FeCl3 added was 0.79g.
4. Use of the oxidoreductase according to claim 1 for the preparation of a medicament for the treatment of tumors, characterized in that: the Fe-tungsten oxide (Fe-WOv) nano enzyme has the combination capability and catalytic activity, can simulate the cascade reaction of catalase and redox active enzyme, and induces the substantial destruction of redox and metabolic steady state of a tumor area, thereby enhancing the tumor treatment effect.
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