CN113244417B - CaO 2 /MnFe 2 O 4 Nanocomposite material, preparation and application thereof - Google Patents

CaO 2 /MnFe 2 O 4 Nanocomposite material, preparation and application thereof Download PDF

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CN113244417B
CN113244417B CN202110378287.1A CN202110378287A CN113244417B CN 113244417 B CN113244417 B CN 113244417B CN 202110378287 A CN202110378287 A CN 202110378287A CN 113244417 B CN113244417 B CN 113244417B
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mnfe
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王香
刘锡建
王星妍
王金霞
管少琪
赵行
曹东苗
张子文
朱同贺
陆杰
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Shanghai University of Engineering Science
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Abstract

The invention discloses CaO 2 /MnFe 2 O 4 The preparation and application of the nano composite material comprise the following steps: with CaCl 2 Adopts a one-step method to prepare PEG modified CaO by using raw materials 2 Nanoparticles; with Fe (acac) 3 And Mn (acac) 2 Preparation of MnFe as raw material 2 O 4 Nanoparticles; taking CaO 2 Ethanol dispersion of nanoparticles, dropwise adding MnFe 2 O 4 The CaO is obtained by ultrasonically stirring ethanol dispersion of the nano particles 2 /MnFe 2 O 4 A nanocomposite material. The composite material of the invention not only can be used for treating cancers by combining ion interference method and chemical kinetics therapy, but also can be used as a contrast agent of MRI to realize diagnosis and treatment. Meanwhile, the composite material has the characteristics of pH response degradation and magnetic targeting, can be metabolized out of a body, and has wide clinical application prospect in the field of biomedicine.

Description

CaO 2 /MnFe 2 O 4 Nanocomposite material, preparation and application thereof
Technical Field
The invention belongs to the technical field of nano composite particle preparation, and relates to CaO 2 /MnFe 2 O 4 Nanocomposite materials, their preparation and use.
Background
Malignant tumors are one of the major diseases seriously harming human health, and are also the leading causes of death worldwide. Chemotherapy, the most traditional treatment, has toxic side effects due to low bioavailability. Under the influence of nontoxic substances released in tumors, fenton reaction can be converted into toxic anticancer substances in situ in the tumor microenvironment, so that the cancer treatment with remarkably enhanced treatment effect and negligible toxic and side effects is realized. MnFe 2 O 4 The nano particle can convert H under neutral condition 2 O 2 Decompose to non-toxic O 2 And H 2 And (O). More importantly, they can efficiently remove H under acidic conditions 2 O 2 Decompose into highly toxic hydroxyl radicals (. OH). Therefore, magnetic nanoparticles are considered as a promising tumor-targeting nanocatalysis enzyme, because hydroxyl radicals are generated in an acidic tumor microenvironment, resulting in apoptosis or necrosis of tumor cells. However, intratumoral H 2 O 2 Too low to generate significant hydroxyl radicals to achieve satisfactory catalytic therapeutic effects.
In order to solve the defect of poor therapeutic effect of the magnetic nanoparticles, many attempts have been made by those skilled in the art. For example, patent CN 202010973050.3 discloses a preparation method and application of copper sulfide/hyperbranched macromolecular nano-bionic enzyme, which uses hyperbranched macromolecular solution and CuCl 2 ·2H 2 O and Na 2 S·9H 2 And O is used as a reactant to prepare CuS @ G5 nano particles, and then the GOD-loaded copper sulfide/hyperbranched macromolecular nano biomimetic enzyme is prepared in sequence. It takes copper sulfide nanoparticle core asThe research shows that the nano bionic enzyme system has excellent chemical kinetics and photothermal treatment performance under the tumor micro-acid environment. However, the product of this patent is not easily degradable and the remaining material may cause damage to vital organs of the organism, resulting in organ failure and death of the organism.
Therefore, the development of the magnetic nanoparticles with good tumor treatment effect, easy degradation and good human safety has great practical significance.
Disclosure of Invention
The invention aims to overcome the defect that the magnetic nanoparticles in the prior art cannot realize good consideration of tumor treatment effect and human safety, and provides the magnetic nanoparticles which have good tumor treatment effect, are easy to degrade and have good human safety.
In order to achieve the purpose, the invention provides the following technical scheme:
CaO 2 /MnFe 2 O 4 nanocomposite material comprising CaO 2 Nanoparticles and coating CaO 2 MnFe of the outer surface of the nanoparticles 2 O 4 Nanoparticles.
Compared with the magnetic nano particle-MnFe in the prior art 2 O 4 Nano particles, caO introduced from outside source 2 Thereby increasing the amount of H in the tumor 2 O 2 Due to MnFe 2 O 4 And CaO 2 All of which are sensitive to pH and are degraded in the tumor environment (under the acidic environment) to release a large amount of ions in the tumor environment, thereby generating hydrogen peroxide and hydroxyl radicals, and CaO 2 The rapid release of degraded calcium ions in the tumor microenvironment can effectively induce calcium overload and calcification, both of which are detrimental to tumor survival. The strategy of combining chemokinetic therapy and ion interference therapy (calcium ion interference method) highlights the availability of the compound in tumor treatment (obviously improves the treatment effect on tumor cells), and opens a new door for further clinical cancer treatment.
As a preferred technical scheme:
CaO as described above 2 /MnFe 2 O 4 Nanocomposite of said CaO 2 /MnFe 2 O 4 The average grain diameter of the nano composite material is 80-200 nm.
The invention also provides CaO as described above 2 /MnFe 2 O 4 The preparation method of the nano composite material comprises the following steps:
(1) With CaCl 2 Adopts a one-step method to prepare PEG modified CaO 2 Nanoparticles; caO modified by PEG 2 The nano particles are stable nano particles, so that the nano particles have better dispersity, are easy to collect, are not easy to degrade and are positively charged;
specifically, caCl is added by one-step method 2 Raw materials, hydrogen peroxide as an oxidant and ammonia water as an auxiliary agent are used for gradually synthesizing CaO 2 Nano particles, which are prepared for the next experiment;
(2) With Fe (acac) 3 Namely iron triacetylacetonate and Mn (acac) 2 Namely, manganese acetylacetonate is used as a raw material to prepare MnFe by a hydrothermal method 2 O 4 The method is mainly used for synthesizing the negatively charged nanoparticles (namely the MnFe) with the particle diameter of less than 10nm 2 O 4 Nano particles) capable of coating CaO on the surface better and more fully through electrostatic adsorption 2 ；
(3) Taking CaO 2 Ethanol dispersion of nanoparticles, dropwise adding MnFe 2 O 4 Ethanol dispersion of nanoparticles, ultrasonic agitation (using ultrasonic-assisted mechanical agitation, synthesized MnFe 2 O 4 The nano-particles have magnetic characteristics, and the synthesized material can be more uniform and has good dispersibility only through mechanical stirring) to obtain the CaO 2 /MnFe 2 O 4 Nanocomposites, i.e. incorporation of MnFe by electrostatic adsorption 2 O 4 The nano particles coat CaO 2 The surface of the nanoparticles makes the whole nanocomposite more pH sensitive, thereby achieving tumor area response release.
The invention firstly synthesizes PEG modified CaO by a one-step method 2 Nano particleThen coating MnFe outside 2 O 4 Nano particles, synthesis of CaO with good dispersity 2 @MnFe 2 O 4 The nano composite material has wide clinical application prospect in the aspects of chemokinetic therapy/ion interference method. Through the biological imaging guide and the magnetic target of the material, the multiple treatment modes are mutually cooperated, and the tumor can be completely eliminated. After treatment, the degradability of the material can reduce the toxic and side effects of the material on organisms.
As a preferable technical scheme:
the preparation method comprises the step (1) of preparing CaO by a one-step method 2 The process of the nano particles is specifically as follows:
taking CaCl 2 Dropping the mixture and PEG solution into anhydrous methanol, and adding H 2 O 2 Stirring with ammonia water (the concentration is 25-28 wt percent) at normal temperature, centrifuging with ethanol, and washing to obtain CaO 2 And dispersing the nano particles in ethanol for later use.
Preparation method as described above, the CaCl 2 、PEG、H 2 O 2 The ratio of the amount of ammonia to the amount of ammonia added is (0.2 to 0.3) g: (0.5-1) mg: (1-3) mL: (0.2-0.3) mL. The protection scope of the present invention is not limited thereto, and those skilled in the art can adjust the ratio of the added amount within a certain range, but the adjustment range is not too large, for example, excessive addition of PEG will cause CaO 2 Agglomeration of nanoparticles (i.e. CaO) 2 The particle size of the nano particles is increased), and further the particle size of the final material is influenced, the addition of PEG is too little, and CaO cannot be ensured 2 Dispersibility of the nanoparticles.
The production method as described above, in step (2), mnFe is produced 2 O 4 The process of the nano particles is specifically as follows:
taking Fe (acac) 3 、Mn(acac) 2 The oleylamine, the oleic acid and the benzyl alcohol are put into a hydrothermal reaction kettle for continuous reaction for 10 hours, and the MnFe is obtained after centrifugation and washing 2 O 4 Nanoparticles.
Preparation method as described above, fe (acac) 3 、Mn(acac) 2 The addition amount ratio of oleylamine, oleic acid and benzyl alcohol is (0.7 to ℃)0.8 G): (0.2-0.3) g: (3-4) mL: (3-4) mL: (10-20) mL; the protection scope of the present invention is not limited thereto, and those skilled in the art can adjust the ratio of the addition amount within a certain range, but the adjustment range is not too large, such as Fe (acac) 3 Or Mn (acac) 2 If the addition amount of (A) is too large, the particle size of the final product is influenced too large; too little oleic acid will affect incomplete reaction, uneven particle size and poor dispersibility.
The temperature of the water bath heating is 180-190 ℃, and the reaction time is 8-10 h. The protection scope of the present invention is not limited thereto, and those skilled in the art can adjust the temperature and reaction time of the water bath heating within a certain range, but the adjustment range is not easy to be too large, and the excessive reaction temperature and the excessive reaction time can cause MnFe 2 O 4 The particle size of the nano particles is too large, so that agglomeration and growth are caused; the reaction temperature is too low, the reaction time is too short, and the reaction of the reagent is incomplete, so that the MnFe is influenced 2 O 4 Yield of nanoparticles.
The production method as described above, in the step (3), caO 2 Nanoparticles and MnFe 2 O 4 The mass ratio of the nano particles is 10-15: 3 to 5. The scope of the present invention is not limited thereto, and those skilled in the art can apply CaO to a certain extent 2 Nanoparticles and MnFe 2 O 4 The mass ratio of the nano particles is adjusted, but the adjustment range is not easy to be overlarge, such as MnFe 2 O 4 If the amount of the nanoparticles added is too small, caO will be formed 2 /MnFe 2 O 4 The catalytic performance and nuclear magnetism effect of the nano composite material are greatly reduced; mnFe 2 O 4 Excessive addition of nanoparticles can result in MnFe 2 O 4 The nanoparticles are free and lost during later processes.
In addition, the invention also provides CaO as described above 2 /MnFe 2 O 4 The application of the nano composite material in preparing tumor diagnosis and treatment reagents, chemical kinetic treatment reagents, biological imaging reagents or pH sensitive degradation reagents.
Has the beneficial effects that:
(1) CaO of the present invention 2 /MnFe 2 O 4 The preparation method of the nano composite material is simple, and the synthesized nano composite material has good dispersibility and smaller particle size;
(2) CaO of the present invention 2 /MnFe 2 O 4 The nano composite material can realize the synergistic effect of the magnetic targeting combined chemical kinetics and the ion interference method;
(3) CaO of the present invention 2 /MnFe 2 O 4 The nano composite material can realize biological imaging, can degrade the pH dependency of the nano composite material, reduces the toxic and side effects on organisms, has good tumor treatment effect and high human safety, and has wide application prospects.
Drawings
FIG. 1 shows CaO obtained in example 1 2 /MnFe 2 O 4 Transmission electron microscopy images of the nanocomposites;
FIG. 2 shows CaO obtained in example 1 2 /MnFe 2 O 4 An elemental map of the nanocomposite;
FIG. 3 shows CaO obtained in example 1 2 /MnFe 2 O 4 The particle size distribution profile of the nanocomposite;
FIG. 4 shows CaO obtained in example 1 2 /MnFe 2 O 4 ROS plots of nanocomposite generation at different pH;
FIG. 5 shows CaO obtained in example 1 2 /MnFe 2 O 4 MRI imaging of the nanocomposite material;
FIG. 6 shows CaO obtained in example 1 2 /MnFe 2 O 4 A plot of hemolysis experiments for the nanocomposite;
FIG. 7 shows CaO obtained in example 1 2 /MnFe 2 O 4 CCK-8 diagram of the nanocomposite.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.
In the following examples, unless otherwise specified, all the materials or treatment techniques are conventional and commercially available materials or conventional treatment techniques in the art, and NH used in the following examples 3 H 2 O is 25 to 28 weight percent.
Example 1
CaO 2 /MnFe 2 O 4 The preparation method of the nano composite material comprises the following steps:
(1) Generally, caO 2 Synthesized at room temperature. 1mL of CaCl was added under vigorous stirring 2 (2 mol/L) and 1mL of PEG (0.5 mg/mL) were added to 60mL of anhydrous methanol. Thereafter, 2mL of H was added 2 O 2 Mixed into the above mixture and then added dropwise with 0.2mL NH three seconds later 3 H 2 And (O). When the reaction lasted 2 hours, caO was obtained by centrifugation 2 And washed with ethanol.
(2)MnFe 2 O 4 The nanoparticles were prepared according to a hydrothermal method. 0.7285g Fe (acac) 3 And 0.2532g Mn (acac) 2 Dissolved in a mixture containing 3.0mL OA (oleic acid), 3.0mL OM (oleylamine), and 10mL benzyl alcohol. After 1 minute of sonication, the solution was reacted in an autoclave at 180 ℃ for 10 hours. The product was collected by magnetic separation and washed several times with ethanol.
(3) First, under mechanical agitation and ultrasonic treatment, 15mgCaO was added 2 Dissolved in 10mL of ethanol. Then 5mg MnFe 2 O 4 Dispersed in 10mL of ethanol, and the dispersion was slowly dropped into the above solution. After 6h of treatment, caO was separated by centrifugation 2 /MnFe 2 O 4 The nanocomposite was washed 3 times with ethanol.
Example 2
CaO 2 /MnFe 2 O 4 Detecting the generated ROS of the composite nano material: the DPBF solution (130. Mu.L, 1 mg/mL) was added to the cuvette first, followed by 600. Mu.g.ml -1 CaO of (2) 2 /MnFe 2 O 4 The nanomaterial was compounded with PBS buffer (pH 6.5 or 7.4) to make the total reaction volume 3ml. The absorbance of DPBF at 410nm was measured at different times.
Example 3
MRI performance test: in vivo magnetic resonance imaging, heLa tumor-bearing mice were injected with 200. Mu.L CaO 2 /MnFe 2 O 4 A nanocomposite material. Mice were scanned before and 3 hours after injection. T2-weighted MRI cross-sectional scan images of mice were obtained.
Example 4
Hemolysis experiment: the red blood cells are washed and diluted phosphate buffer solution is mixed with CaO 2 /MnFe 2 O 4 The nanocomposites were at different concentrations (6.25-100. Mu.g/mL) and stored for 4h at room temperature using deionized water and PBS as positive and negative controls. Then, the supernatant is obtained by centrifugation, and the hemolysis rate is determined and calculated.
Example 5
Evaluation of cytotoxicity: cells were plated at 1X 10 per well 4 Density plated in 96-well plates and placed at 37 ℃ 5% 2 Incubate for 24h under conditions. Next, caO containing different concentrations (0, 6.25, 12.5, 25, 50, 100, 200. Mu.g/mL, 400. Mu.g/mL) was used 2 /MnFe 2 O 4 The original medium was replaced with fresh medium, and after further culturing for 24 hours, the medium was replaced with a medium solution containing 10% of CCK-8, and further culturing was continued for 1 hour, and the OD value per well (detection wavelength: 450 nm) was measured on a microplate reader.
The final products synthesized in the above examples were characterized as shown in FIGS. 1-7:
as can be seen from the transmission electron microscope of FIG. 1 and the mapping of FIG. 2, caO was successfully synthesized 2 /MnFe 2 O 4 Nano material and small grain size.
As can be seen from the particle size diagram of FIG. 3, caO 2 /MnFe 2 O 4 The particle size of (A) is uniform and the hydrated particle size is about 150 nm.
As can be seen from FIG. 4, caO 2 /MnFe 2 O 4 Compared with pH7.4, the nanocomposite generates more ROS in PBS buffer solution with pH6.5, which indicates that the nanocomposite degrades under acidic conditions and can effectively generate a large amount of ROS so as to kill tumor cells.
As can be seen from FIG. 5, the nanocomposite CaO 2 /MnFe 2 O 4 The nuclear magnetic signal in the tumor area is obvious, which indicates that the nano composite material is suitable to be used as an MRI imaging contrast agent for MRI imaging.
As can be seen from the hemolysis experiment of FIG. 6, caO, the material 2 /MnFe 2 O 4 The hemolysis rate of (2) is low, which shows that the material has excellent biocompatibility and water solubility and can be used for in vivo experiments.
As can be seen from the CCK-8 experiment of FIG. 7a, normal cells and high CaO concentration 2 /MnFe 2 O 4 The survival rate is still about 80% when the materials are cultivated, and the low toxicity of the materials is proved. As can be seen from FIG. 7b, the survival rate of tumor cells at pH6.5 was significantly lower than that at pH7.4 when the material was incubated with tumors of different pH, demonstrating that the material had a good effect of killing tumor cells in an acidic response.
Example 6
CaO 2 /MnFe 2 O 4 The preparation method of the nano composite material comprises the following steps:
(2) Generally, caO 2 Synthesized at room temperature. Under vigorous stirring, 1mL of CaCl 2 (2 mol/L) and 1mL of PEG (0.5 mg/mL) were added to 60mL of anhydrous methanol. Thereafter, 1mL of H 2 O 2 Mixed into the above mixture and then added dropwise with 0.2mL NH three seconds later 3 H 2 And O. When the reaction lasted 2 hours, caO was obtained by centrifugation 2 And washed with ethanol.
(2)MnFe 2 O 4 The nanoparticles were prepared according to a hydrothermal method. 0.73g Fe (acac) 3 And 0.26g Mn (acac) 2 Dissolved in a mixture containing 3.0mL OA (oleic acid), 3.0mL OM (oleylamine), and 10mL benzyl alcohol. After 1 minute of sonication, the solution was reacted in an autoclave at 180 ℃ for 10 hours. The product was collected by magnetic separation and washed several times with ethanol.
(3) First, 10mgCaO was added under mechanical agitation and ultrasonic treatment 2 Dissolved in 10mL of ethanol. Then 3mgMnFe 2 O 4 DispersingIn 10mL of ethanol, and the dispersion was slowly dropped into the above solution. After 6h of treatment, caO was separated by centrifugation 2 /MnFe 2 O 4 The nanocomposite was washed 3 times with ethanol.
Example 7
CaO 2 /MnFe 2 O 4 The preparation method of the nano composite material comprises the following steps:
(1) Generally, caO 2 Synthesized at room temperature. Under vigorous stirring, 1mL of CaCl 2 (2.1 mol/L) and 1mL of PEG (0.5 mg/mL) were added to 60mL of anhydrous methanol. Thereafter, 2mL of H 2 O 2 Mixed into the above mixture and then added dropwise with 0.3mL of NH three seconds later 3 H 2 And (O). When the reaction lasted 2 hours, caO was obtained by centrifugation 2 And washed with ethanol.
(2)MnFe 2 O 4 The nanoparticles were prepared according to a hydrothermal method. Mixing 0.75gFe (acac) 3 And 0.26g Mn (acac) 2 Dissolved in a mixture containing 3.0mL OA (oleic acid), 3.0mL OM (oleylamine) and 10mL benzyl alcohol. After 1 minute of sonication, the solution was reacted in an autoclave at 180 ℃ for 10 hours. The product was collected by magnetic separation and washed several times with ethanol.
(3) Firstly, under mechanical stirring and ultrasonic treatment, 15mg CaO is added 2 Dissolved in 10mL of ethanol. Then 5mg of MnFe 2 O 4 Dispersed in 10mL of ethanol, and the dispersion was slowly dropped into the above solution. After 6h of treatment, caO was separated by centrifugation 2 /MnFe 2 O 4 The nanocomposite was washed 3 times with ethanol.
Example 8
CaO 2 /MnFe 2 O 4 The preparation method of the nano composite material comprises the following steps:
(1) Generally, caO 2 Synthesized at room temperature. Under vigorous stirring, 1mL of CaCl 2 (2 mol/L) and 2mL of PEG (0.5 mg/mL) were added to 60mL of anhydrous methanol. After that, 3mL of H 2 O 2 Mixed into the above mixture and then added dropwise with 0.3mL NH three seconds later 3 H 2 And (O). When the reaction lasted 2 hours, caO was obtained by centrifugation 2 And washed with ethanol.
(2)MnFe 2 O 4 The nanoparticles were prepared according to a hydrothermal method. 0.73g of Fe (acac) 3 And 0.25g Mn (acac) 2 Dissolved in a mixture containing 3.0mL OA (oleic acid), 3.0mL LOM (oleylamine) and 10mL benzyl alcohol. After 1 minute of sonication, the solution was reacted in an autoclave at 180 ℃ for 10 hours. The product was collected by magnetic separation and washed several times with ethanol.
(3) First, under mechanical agitation and ultrasonic treatment, 15mgCaO was added 2 Dissolved in 10mL of ethanol. Then 5mg MnFe 2 O 4 Dispersed in 10mL of ethanol, and the dispersion was slowly dropped into the above solution. After 6h of treatment, caO was separated by centrifugation 2 /MnFe 2 O 4 The nanocomposite was washed 3 times with ethanol.
The embodiments described above are intended to facilitate a person of ordinary skill in the art in understanding and using the invention. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make modifications and alterations without departing from the scope of the present invention.

Claims (3)

1.CaO 2 /MnFe 2 O 4 Nanocomposite material, characterized in that it comprises CaO 2 Nanoparticles and coating CaO 2 MnFe of the outer surface of the nanoparticles 2 O 4 Nanoparticles; said CaO being 2 /MnFe 2 O 4 The average grain diameter of the nano composite material is 80 to 200nm; said CaO being 2 /MnFe 2 O 4 The preparation method of the nano composite material comprises the following steps:
(1) With CaCl 2 Adopts a one-step method to prepare PEG modified CaO by using raw materials 2 Nanoparticles; one-step method for preparing CaO 2 Nano-particleThe sub-process specifically comprises the following steps:
taking CaCl 2 Dropping the mixture and PEG solution into anhydrous methanol, and adding H 2 O 2 Mixing with ammonia water, stirring at normal temperature, centrifuging with ethanol, and washing to obtain CaO 2 Nano particles, and dispersing in ethanol for later use; said CaCl 2 、PEG、H 2 O 2 The ratio of the amount of the ammonia to the amount of the ammonia added is (0.2 to 0.3) g: (0.5 to 1) mg: (1 to 3) mL: (0.2 to 0.3) mL; the concentration of ammonia water is 25 to 28wt%;
(2) With Fe (acac) 3 And Mn (acac) 2 Preparation of MnFe as raw material 2 O 4 Nanoparticles; the process specifically comprises the following steps:
taking Fe (acac) 3 、Mn(acac) 2 The oleylamine, the oleic acid and the benzyl alcohol are put into a hydrothermal reaction kettle for continuous reaction, centrifugation and washing to obtain MnFe 2 O 4 Nanoparticles; fe (acac) 3 、Mn(acac) 2 The addition amount ratio of oleylamine, oleic acid and benzyl alcohol is (0.7 to 0.8) g: (0.2 to 0.3) g: (3 to 4) mL: (3 to 4) mL: (10 to 20) mL; the temperature of water bath heating is 180 to 190 ℃, and the reaction time is 8 to 10 hours;
(3) Taking CaO 2 Ethanol dispersion of nanoparticles, dropwise adding MnFe 2 O 4 The CaO is obtained by ultrasonically stirring ethanol dispersion of the nano particles 2 /MnFe 2 O 4 A nanocomposite material; caO (CaO) 2 Nanoparticles and MnFe 2 O 4 The mass ratio of the nanoparticles is 10 to 15:3 to 5.
2. CaO according to claim 1 2 /MnFe 2 O 4 Use of a nanocomposite for the preparation of a chemokinetic therapeutic agent, a bioimaging agent or a pH sensitive degradation agent.
3. CaO according to claim 1 2 /MnFe 2 O 4 The application of the nano composite material in preparing a tumor diagnosis and treatment reagent.
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