CN113332445A - CaO2Cu-ferrocene multifunctional nano-particles and preparation method thereof - Google Patents

CaO2Cu-ferrocene multifunctional nano-particles and preparation method thereof Download PDF

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CN113332445A
CN113332445A CN202110525649.5A CN202110525649A CN113332445A CN 113332445 A CN113332445 A CN 113332445A CN 202110525649 A CN202110525649 A CN 202110525649A CN 113332445 A CN113332445 A CN 113332445A
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ferrocene
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李翔
孔涵靖
傅译可
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ZJU Hangzhou Global Scientific and Technological Innovation Center
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Abstract

The invention discloses CaO2The Cu-ferrocene multifunctional nano-particles and the preparation method and the application thereof, the preparation method comprises the following steps: adding CaO2Dispersing the nano particles into N, N-dimethylformamide solution containing polyvinylpyrrolidone, then sequentially adding a copper source and ferrocene dicarboxylate, reacting, and centrifugally washing to obtain CaO2Cu-ferrocene multifunctional nano-particles. To solve the problem of low CDT efficiency and single function existing in the related technologyTo give a title. Aiming at the existing CDT, the method aims to realize the synergy of self-supply hydrogen peroxide enhanced CDT and a calcium ion interference method and improve the effect of tumor treatment. The application effect of the composite nano-particles is well proved in vitro or in a mouse.

Description

CaO2Cu-ferrocene multifunctional nano-particles and preparation method thereof
Technical Field
The invention belongs to the field of biological nano materials, and particularly relates to CaO2A Cu-ferrocene multifunctional nano-particle and a preparation method thereof.
Background
Cancer is one of the diseases that currently seriously threaten human health. Lack of effective early diagnosis and selective treatment means has led to its becoming a major cause of human death. Traditional tumor treatment means include surgery, radiotherapy and chemotherapy. The three methods have respective disadvantages, and can not effectively cure the tumor and inhibit the recurrence of the cancer; in addition, potential side effects result from the inability to specifically recognize tumor tissue and normal tissue. Thus, the problems associated with a single conventional treatment approach have forced the development of a more cell-selective, safer cancer treatment. For this reason, the scientific community has proposed the concept of targeted therapy, which focuses the drug more on the tumor site and reduces its enrichment in normal tissues. The nano-particles also have higher surface energy due to the small-size effect, and can be used as a new way for tumor targeted therapy by carrying out surface modification on the nano-particles.
Fe based on a highly expressed microenvironment of tumor acidity and hydrogen peroxide2+/Fe3+Introduction of tumor tissue is expected to elicit a fenton reaction. The fenton reaction is a reaction that catalyzes hydrogen peroxide to generate a toxic hydroxyl radical (OH) under acidic conditions, and can oxidize most organic substances, and the reaction chemical formula is shown in formula (1) (2). Under acidic conditions, ferric/ferrous ions typically act as catalysts for hydrogen peroxide to complete the reaction. Researchers have proposed an emerging therapeutic strategy as chemokinetic therapy (CDT) and defined it as an in situ treatment that utilizes the fenton or fenton-like response to generate OH at the tumor site. In brief, ferrous ions are dissolved in the iron-based nano material under the weak acid condition of a tumor microenvironment to trigger a Fenton reaction to catalyze hydrogen peroxide to generate OH, and the OH triggers apoptosis by damaging biological macromolecules such as DNA (deoxyribonucleic acid), protein and the like to inhibit tumors. Most importantly, the method ensures the safety of normal tissues to a certain extent, because the fenton reaction is greatly inhibited in the normal tissue environment (weak alkaline condition, insufficient hydrogen peroxide). Compared with chemotherapy, radiotherapy, photothermal therapy and photodynamic therapy, CDT has the advantages of 1) strong selectivity; 2) activated by endogenous stimuli. In addition, except Fe2+In addition to the catalytic action of (2), Mn2+、Ti3+、Cu2+、Co2+Such transition metal ions may also act as catalysts.
Fe2++H2O2＝Fe3++·OH+HO- (1)
Fe3++H2O2＝Fe2++·OOH+H+ (2)
In the process of implementing the invention, the inventor finds that at least the following problems exist in the prior art:
the single CDT is limited by the complex physiological environment of the tumor, such as limited hydrogen peroxide content and high expressed glutathione levels. Disclosure of Invention
The embodiment of the application aims at providing CaO2The Cu-ferrocene multifunctional nano-particle, the preparation method and the application thereof solve the problems of low CDT efficiency and single function in the related technology. Aiming at the existing CDT, the method aims to realize the synergy of self-supply hydrogen peroxide enhanced CDT and a calcium ion interference method and improve the effect of tumor treatment. The application effect of the composite nano-particles is well proved in vitro or in a mouse.
According to a first aspect of embodiments of the present application, there is provided CaO2The preparation method of the/Cu-ferrocene multifunctional nano-particles comprises the following steps:
adding CaO2Dispersing the nano particles into N, N-dimethylformamide solution containing polyvinylpyrrolidone, then sequentially adding a copper source and ferrocene dicarboxylate, reacting, and centrifugally washing to obtain CaO2Cu-ferrocene multifunctional nano-particles.
Preferably, said CaO2The nanoparticles are prepared by a wet chemical process.
Preferably, said CaO2The ratio of the nano particles to the N, N-dimethylformamide solution is (5-5.3): 16 (mg/mL).
Preferably, the ratio of the polyvinylpyrrolidone PVP to the N, N-dimethylformamide solution is (10-12): 1 (mg/mL).
Preferably, the polyvinylpyrrolidone PVP-K30 has an average molecular weight of 45,000-58,000.
Preferably, the centrifugation speed is 10000-.
Preferably, the copper source is selected from one of copper acetate, copper sulfate and copper nitrate.
Preferably, the molar ratio of the copper source to the ferrocene dicarboxylate is 1:1, and the ratio of the copper source to the N, N-dimethylformamide solution is as follows: (0.01-0.02): 16 (mmol/mL).
Preferably, the washing is performed with N, N-dimethylformamide and absolute ethanol, respectively.
According to a first aspect of embodiments of the present application, there is provided CaO prepared by the preparation method of the first aspect2Cu-ferrocene multifunctional nano-particles.
According to a first aspect of embodiments of the present application, there is provided CaO according to the first aspect2Application of the Cu-ferrocene multifunctional nano-particles in preparing a preparation for synergetic treatment of chemical power and calcium overload of tumors.
The technical scheme provided by the embodiment of the application can have the following beneficial effects:
from the above examples, it is clear that the present application is directed to CaO2The copper-based ferrocene molecules are coated on the surfaces of the nano particles, so that sufficient hydrogen peroxide can be generated at tumor parts and glutathione can be consumed, and therefore, the composite nano particles overcome the defects of limited hydrogen peroxide and overhigh level of glutathione at the tumor parts, and the effect of sensitization chemical power and calcium overload synergistic treatment is achieved.
CaO prepared by the embodiment of the invention2The nano particles generate hydrogen peroxide under an acidic condition, so that the occurrence of a fenton reaction catalyzed by ferrocene is enhanced; more importantly, except CaO2Induced exogenous Ca2+In addition, enhanced ROS production promotes intracellular calcium accumulation by modulating the calcium ion channels of tumor cells. Therefore, the promotion of OH production in tumor cells by the system is coordinated with calcium overload, so that the in vitro and in vivo anti-tumor phenomenon is obvious. The composite nano-particle can simultaneously realize the induction of OH generation and glutathione and calcium overload consumption by self-supplied hydrogen peroxide, and has important significance in tumor treatment. In addition, forSome fenton reaction-based applications also have some practical value.
In the present invention, CaO having a uniform size and a good dispersibility is used2The surface of the nano-particle is coated with copper-based ferrocene molecules to realize the synergistic treatment effect of sensitization chemical power and calcium overload. To date, no application based on the synergy of chemical kinetics and calcium ion overload has been developed in the art. The present invention fills this gap. The preparation method has the advantages of simple process, low price, good dispersion stability and the like, and is suitable for large-scale production.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the application.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and together with the description, serve to explain the principles of the application.
FIG. 1 shows CaO in an example of the present invention2Electron microscope images of/Cu-ferrocene nano-particles, wherein (a) is a scanning electron microscope image, and (b) is a transmission electron microscope image.
FIG. 2 shows CaO in an example of the present invention2Distribution pattern of Ca, Cu and Fe elements in Cu-ferrocene nano-particles.
FIG. 3 shows CaO in an example of the present invention2XRD pattern of/Cu-ferrocene nano-particles.
FIG. 4 shows CaO in an example of the present invention2And CaO2Zeta potential diagram of/Cu-ferrocene nanoparticles.
FIG. 5 shows CaO in an example of the present invention2And CaO2The hydrodynamic radius of the/Cu-ferrocene nano-particles.
FIG. 6 shows CaO in an example of the present invention2The XPS spectrum of Cu-ferrocene nano particles is shown in the specification, wherein (a) is a full spectrum, (b) is an XPS high-resolution spectrum of Cu 2p, and (c) is an XPS high-resolution spectrum of Fe 2 p.
FIG. 7 shows CaO in an example of the present invention2And CaO2Change in pH of Cu-ferrocene nanoparticles in buffer solution.
FIG. 8 shows CaO at various pH conditions in examples of the present invention2And CaO2Hydrogen peroxide release profile of/Cu-ferrocene nanoparticles.
FIG. 9 shows CaO concentrations in different examples of the present invention2Glutathione consumption by Cu-ferrocene nanoparticles as a function of time.
FIG. 10 shows CaO in an example of the present invention2Fenton performance characterization of/Cu-ferrocene nanoparticles, wherein (a) is an absorption spectrum chart, and (b) is a kinetic curve.
FIG. 11 shows CaO at various pH conditions in examples of the present invention2ESR spectrum of/Cu-ferrocene nano-particles.
FIG. 12 shows CaO in an example of the present invention2Cytotoxicity verification of Cu-ferricene nanoparticles wherein (a) CaO is present in different concentrations2The cell compatibility of Cu-ferrocene nano-particles, (b) CaO under different pH conditions2Killing ability of Cu-ferrocene nano-particles on mouse breast cancer cells (4T1), and (c) different concentrations of CaO2Killing ability of Cu-ferrocene nano-particles to 4T1 cells after 24 hours and 48 hours of culture respectively.
FIG. 13 shows CaO in an example of the present invention2Intracellular hydrogen peroxide detection of 4T1 cells after Cu-ferrocene nanoparticle treatment.
FIG. 14 shows CaO at various pH conditions in examples of the invention2Detection of intracellular reactive oxygen species in 4T1 cells after Cu-ferrocene nanoparticle treatment.
FIG. 15 shows CaO concentrations at different levels in examples of the present invention2Detection of intracellular glutathione in 4T1 cells after Cu-ferrocene nanoparticle treatment.
FIG. 16 shows CaO concentrations at different levels in examples of the present invention2Detection of intracellular calcium ion of 4T1 cells after Cu-ferrocene nanoparticle treatment.
FIG. 17 shows CaO in an example of the present invention2Intracellular Calpain-1, PMCA4, TRPA1, BAX, Bcl-2 and Caspase-3 protein expression of 4T1 cells after Cu-ferrocene nanoparticle treatment.
FIG. 18 is a graph showing the change in body weight of mice in each group according to the example of the present invention.
FIG. 19 shows CaO in examples of the present invention2The in vivo anti-tumor effect graph of the Cu-ferrocene nano-particles is shown in the specification, wherein (a) is an optical photo of tumors of each group of mice on the fourteenth day, (b) is the tumor weight of each group of mice on the fourteenth day, (c) is the volume change curve of the tumors of each group of mice, and (d) is the tumor section of each group of mice.
Detailed Description
Reference will now be made in detail to the exemplary embodiments, examples of which are illustrated in the accompanying drawings. When the following description refers to the accompanying drawings, like numbers in different drawings represent the same or similar elements unless otherwise indicated. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present application. Rather, they are merely examples of apparatus and methods consistent with certain aspects of the present application, as detailed in the appended claims.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in this application and the appended claims, the singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items.
The invention is further described with reference to the following figures and specific examples.
The embodiment of the invention provides CaO2Cu-ferrocene multifunctional nano-particles. Under acidic conditions, the particles can rapidly release Ca2+And hydrogen peroxide, while the particles remain relatively stable under neutral conditions. In addition, hydrogen peroxide reacts with ferrocene molecules in a Fenton reaction to generate OH, while glutathione is Cu-substituted2+Consumption, potential consumption of OH is avoided. In addition, exogenous Ca is released from the granule itself2+In addition, the large number of hydroxyl radicals generated by the reaction can promote intracellular calcium accumulation by modulating calcium channel proteins. The results indicate that increased levels of oxidative stress and intracellular calcium overload lead to in vitro and in vivo anti-edemaThe tumor phenomenon is remarkable.
The present invention will be described in detail by examples. It is to be understood that the following examples are illustrative of the present invention and are not to be construed as limiting the scope of the invention, and that certain insubstantial modifications and adaptations of the invention by those skilled in the art in light of the foregoing description are intended to be included within the scope of the invention. The specific process parameters and the like of the following examples are also merely examples of suitable ranges, i.e., those skilled in the art can select the appropriate ranges through the description herein, and are not limited to the specific values exemplified below.
Example 1
CaO2The preparation method of the/Cu-ferrocene multifunctional nano-particles can comprise the following steps:
5mg of CaO was weighed2The nanoparticles were dispersed in 16mL of N, N-Dimethylformamide (DMF) containing polyvinylpyrrolidone (PVP) (10mg/mL) and stirred at room temperature. 0.01mmol of copper acetate and 0.01mmol of ferrocene dicarboxylate were weighed and added to CaO in this order2Reacting with mixed solution of PVP for 1 hour under the condition of 80 ℃ water bath, taking out after cooling, centrifugally separating reaction products at 12000rpm, washing 3 times with DMF (dimethyl formamide), washing 2 times with ethanol, and centrifuging to obtain copper-based ferrocene-coated CaO2And (3) nanoparticles.
Example 2
5.3mg CaO was weighed2The nanoparticles were dispersed in 16mL of a DMF solution containing PVP (12mg/mL) and stirred at room temperature. 0.02mmol of copper acetate and 0.02mmol of ferrocene dicarboxylate are weighed and added to CaO in sequence2Reacting with PVP mixed solution for 0.5 hour under the condition of 80 ℃ water bath, cooling, taking out, centrifugally separating a reaction product at 10000rpm, washing 3 times with DMF (dimethyl formamide), washing 2 times with ethanol, and centrifuging to obtain copper-based ferrocene coated CaO2And (3) nanoparticles.
In FIG. 1, (a) and (b) are CaO, respectively2SEM and TEM images of/Cu-ferricene nanoparticles, it can be seen that CaO2The size of the/Cu-ferrocene nano-particles is about 80 nanometers and the particles are uniformly dispersed. From FIG. 2, it can be seen that Ca, Cu and Fe elementsThe elements are uniformly distributed on the surface of the particles, and the content of calcium ions is relatively high. The XRD pattern of fig. 3 shows only the phase of calcium peroxide, indicating that the copper-based ferrocene on the surface of calcium peroxide exists in an amorphous state. As can be seen from FIG. 4, after copper-based ferrocene is coated, the electrical property of the particle surface becomes negative; while its hydrodynamic radius increases (fig. 5). Both of which describe CaO2Successful preparation of Cu-ferrocene nanoparticles. As can be seen from fig. 6, the final material contains elements Ca, Cu and Fe, where the valence states of both copper and iron are + 2.
Note that CaO in the above two examples2The nanoparticles are prepared by a wet chemical method, which is an existing method and will not be described herein. The polyvinylpyrrolidone of this example is preferably PVP-K30, having an average molecular weight of 45,000-58,000, although other signals are possible.
In the above examples, copper acetate is used as the copper source, and if other copper salts are selected, some adjustment is required in the preparation time and temperature, and the adjustment can be obtained according to the embodiments of the present invention by combining with the common knowledge in the art.
Example 3
This example provides a CaO obtained as described above2The application of the Cu-ferrocene multifunctional nano-particles in preparing a preparation for the synergistic treatment of the chemical power and the calcium overload of tumors comprises the following steps: prepared CaO2the/Cu-ferrocene nano-particles are centrifuged and re-dispersed in an aqueous solution system, and a corresponding therapeutic preparation is obtained after sterilization.
Example 4
Capacity of the material to produce hydrogen peroxide: after adding 1mg of CaO2Nanoparticles and CaO containing the same calcium ion content2the/Cu-ferrocene nanoparticles were dissolved in 1mL of acetic acid buffer solutions with different pH values (5/7). A small amount of liquid was removed at different time nodes and the supernatant was centrifuged. mu.L of the supernatant and 300. mu.L of horseradish peroxidase (HRP, concentration 1U/mL) were added to 1.68mL of Phosphate Buffered Saline (PBS). After 10 minutes of reaction, 300. mu.L of 3,3',5,5' -Tetramethylbenzidine (TMB) was added to the above solution. Generated hydrogen peroxideThe content is obtained by measuring the ultraviolet-visible light absorption spectrum of the solution.
As can be seen from FIG. 7, CaO2The nanoparticles produced a large amount of hydrogen peroxide under acidic conditions, and the rate and total amount of hydrogen peroxide released from copper-based ferrocene grafted was significantly reduced, probably due to the fenton effect of ferrocene that consumed a portion of the hydrogen peroxide. CaO (CaO)2the/Cu-ferrocene nano-particles can effectively release hydrogen peroxide under acidic conditions, and basically do not generate hydrogen peroxide under neutral conditions. The above results demonstrate CaO2the/Cu-ferrocene nano-particles have an acidic response hydrogen peroxide release characteristic and can keep relative stability under a neutral condition. In addition, calcium peroxide hydrolysis produces calcium hydroxide, which increases the alkalinity of the solution. As can be seen from FIG. 8, the pH of the solution changed less under the protection of copper-based ferrocene.
Example 5
Glutathione-consuming capacity of the material: CaO with different masses is added at 37 DEG C2the/Cu-ferrocene nanoparticles were dispersed in 6mL of glutathione solution (concentration 1.5mM, pH 7). A small amount of liquid was removed at different time nodes and the supernatant was centrifuged. Then 500. mu.L of the supernatant and 50. mu.L of 5,5' -dithiobis (2-nitrobenzoic acid) (DTNB) were added to 2.5mL of PBS. The content of the glutathione is obtained by measuring the ultraviolet visible light absorption spectrum of the solution and corresponding to a standard curve. It can be confirmed from FIG. 9 that CaO2the/Cu-ferrocene nano-particles can continuously consume glutathione.
Example 6
Fenton performance of the material: CaO (CaO)2The Fenton performance of the/Cu-ferrocene nano-particles is detected by TMB color development. 300 μ L of TMB (8mM) and different concentrations of material were added sequentially to 3mL of acetic acid buffer solution. The absorption curve and the kinetic curve over time of the solution were determined with an ultraviolet-visible spectrophotometer. In addition, the signal peak of hydroxyl radical was detected by electron spin resonance spectroscopy (ESR), and 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) was used as a trapping agent.
As can be seen from FIGS. 10(a, b), under acidic conditions, ferrocene reacts with hydrogen peroxide supplied by itself to produce a Fenton reaction, which develops color in TMB. At the same time, ESR confirmed that the product of the reaction was a hydroxyl radical (fig. 11).
Example 7
The experiment shows the application of the material in the specific killing of tumor cells through the killing effect on the cell layer. The first is the biocompatibility of the material, and the normal cells used are human liver cells (HL-7702) and mouse mononuclear macrophages (RAW 264.7). The co-culture of normal cells with different concentrations of the material, as shown in fig. 12 (a), can be seen in a certain concentration range, the material has better biocompatibility. On the contrary, the material has obvious killing effect on tumor cells (4T1 mouse breast cancer cells). As can be seen from fig. 12(b), the killing effect of the material at the same concentration is significantly enhanced under acidic conditions, since the acidic conditions favor the occurrence of fenton reaction, resulting in the generation of toxic hydroxyl radicals. In addition to the concentration dependence, it can be seen from (c) in fig. 12 that the killing effect of the material after 48 hours is significantly stronger than 24 hours.
The killing mechanism of the material to the tumor cells is further explored by detecting various indexes in the cells. First, the hydrogen peroxide content in the cells was detected by the hydrogen peroxide kit, and as can be seen from fig. 13, the hydrogen peroxide content in the material-treated 4T1 cells was significantly increased compared to the control group. The material was shown to act intracellularly and produce Reactive Oxygen Species (ROS) by detecting ROS production intracellularly. DCFH-DA is a probe for detecting ROS, has ROS sensitive action, is oxidized into DCF with high fluorescence intensity under the action of ROS, and can emit green light under the excitation of blue light. As can be seen from fig. 14, the material-treated cells produced a large amount of ROS compared to the blank control, and the generation of ROS was more pronounced under acidic conditions. Intracellular glutathione content was also measured using naphthalene-2, 3-dicarbaldehyde (NDA), and figure 15 shows: the fluorescence intensity of the glutathione in the cells treated by the material is obviously reduced. As the expression of calcium overload on the cellular level, the increase of intracellular calcium ion level is an important index. Fluo-4AM is a fluorescent probe for the detection of intracellular calcium ions. As can be seen from FIG. 16, the fluorescence intensity of calcium ions in the cells treated with the material was significantly increased, indicating that the material was effective in increasing the level of intracellular calcium ions.
In fact, ROS can regulate calcium ion channels by altering protein expression, further regulating intracellular calcium ion content. FIG. 17 shows the measurement of the expression of a specific protein in a cell by Western Blotting (WB). The increase of Calpain-1 as a calmodulin also proves the increase of the level of calcium ions in cells; cell membrane calcium atpase 4(PMCA4) is a calcium efflux pump on the cell membrane, while transient receptor ion potential channel (TRPA1) is a channel protein that regulates calcium influx. From the WB results, it can be seen that the material-treated cells were inhibited in the expression of PMCA4 and increased in the expression of TRPA1, and the combination of both finally resulted in the accumulation of intracellular calcium ions. In addition, activation of mitochondrial apoptotic pathways was demonstrated by alterations in the expression of apoptosis-related proteins such as Bcl-2, BAX and Caspase-3.
Example 8
The experiment shows the application of the material in killing tumor cells by killing tumors on an animal (mouse) level. 4T1 tumor-transplanted mice were randomly divided into four groups. The mice were treated on days 0, 2, 4, and 8 after successful tumor bearing, respectively, the first group was injected with PBS solution, and the second group was injected with 100. mu.g CaO per mouse2Nanoparticles, third group of mice injected with 100 μ g CaO per mouse2Cu-ferrocene nanoparticles, fourth group of mice injected with 300. mu.g CaO per mouse2Cu-ferrocene nano-particles. The body weight of the mice and the size of their tumors were measured and recorded every other day. As can be seen in fig. 18, there was no significant change in body weight in all mice, indicating that the above treatment had no significant effect on the normal physiological activity of the mice. As can be seen from FIG. 19, CaO was present in comparison with the control group2And CaO2The Cu-ferrocene nano-particles have different degrees of inhibition effects on tumors. Comparing the two groups 2 and 3, CaO can be found2The Cu-ferrocene nano-particles have stronger inhibition effect on tumors. To further verify the killing effect of the material on tumor tissue, tumor needs to be treatedPathological section of tumor tissue (H)&E) And immunohistochemical (ki67) analysis. As can be seen from the section of the tumor tissue, the tumor tissue treated by the material obviously has the typical morphological characteristics of apoptosis. H&E staining shows phenomena such as vacuolation and nuclear contraction, ki67 shows that the material has obvious inhibition effect on tumor proliferation, which is consistent with the in vitro experiment result.
Other embodiments of the present application will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. This application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the application and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the application being indicated by the following claims.
It will be understood that the present application is not limited to the precise arrangements described above and shown in the drawings and that various modifications and changes may be made without departing from the scope thereof. The scope of the application is limited only by the appended claims.

Claims (10)

1. CaO2The preparation method of the/Cu-ferrocene multifunctional nano-particles is characterized by comprising the following steps:
adding CaO2Dispersing the nano particles into N, N-dimethylformamide solution containing polyvinylpyrrolidone, then sequentially adding a copper source and ferrocene dicarboxylate, reacting, and centrifugally washing to obtain CaO2Cu-ferrocene multifunctional nano-particles.
2. The method according to claim 1, wherein said CaO is added to said molten steel2The nanoparticles are prepared by a wet chemical process.
3. The method according to claim 1, wherein said CaO is added to said molten steel2The ratio of the nano particles to the N, N-dimethylformamide solution is (5-5.3): 16 (mg/mL).
4. The preparation method according to claim 1 or 3, wherein the ratio of polyvinylpyrrolidone PVP to N, N-dimethylformamide solution is (10-12): 1 (mg/mL).
5. The method for preparing the polyvinyl pyrrolidone of claim 1, wherein the polyvinyl pyrrolidone is polyvinyl pyrrolidone PVP-K30.
6. The method according to claim 1, wherein the copper source is selected from one of copper acetate, copper sulfate, and copper nitrate.
7. The preparation method according to claim 1, wherein the molar ratio of the copper source to the ferrocene dicarboxylate is 1:1, and the ratio of the copper source to the N, N-dimethylformamide solution is as follows: (0.01-0.02): 16 (mmol/mL).
8. The method according to claim 1, wherein the washing is carried out with N, N-dimethylformamide and absolute ethanol, respectively.
9. CaO prepared by the preparation method of claim 12Cu-ferrocene multifunctional nano-particles.
10. CaO in accordance with claim 12Application of the Cu-ferrocene multifunctional nano-particles in preparing a preparation for synergetic treatment of chemical power and calcium overload of tumors.
CN202110525649.5A 2021-05-13 2021-05-13 CaO2Cu-ferrocene multifunctional nano-particles and preparation method thereof Pending CN113332445A (en)

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