CN113855815A - Zinc-containing metal organic framework coated manganese dioxide nanocomposite and preparation and application thereof - Google Patents

Zinc-containing metal organic framework coated manganese dioxide nanocomposite and preparation and application thereof Download PDF

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CN113855815A
CN113855815A CN202111097053.6A CN202111097053A CN113855815A CN 113855815 A CN113855815 A CN 113855815A CN 202111097053 A CN202111097053 A CN 202111097053A CN 113855815 A CN113855815 A CN 113855815A
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zinc
manganese dioxide
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刘锡建
管少琪
王星妍
王金霞
张子文
曹东苗
王香
陆杰
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Shanghai University of Engineering Science
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Abstract

The invention relates to a zinc-containing metal organic framework coated manganese dioxide nano composite material and a preparation method thereofThe preparation and application of the composite material are as follows: (1) ZIF-90 which is formed by complexing Zn ions serving as nodes and imidazole-2-formaldehyde serving as an organic ligand; (2) by oxidation-reduction of MnO2Coating the outer layer to obtain the target product. The zinc-containing metal organic framework coated manganese dioxide nano composite material has a porous dodecahedron structure, and provides a space for effectively delivering adriamycin (DOX) to tumor tissues, and the composite material not only can integrate the reinforcement of sonodynamic therapy under oxidative stress and the overcoming of drug resistance of chemotherapeutic drugs, realizes sonodynamic therapy/chemotherapy synergistic therapy on cancer, but also can be used as an MR (magnetic resonance) contrast agent; in addition, the composite material has double sensitive degradation effects on weak acid environment of tumor and ultrasonic irradiation, can reduce the long-term toxicity of the composite material to organisms, and has wide application prospect in the field of biomedicine.

Description

Zinc-containing metal organic framework coated manganese dioxide nanocomposite and preparation and application thereof
Technical Field
The invention belongs to the technical field of nano composite particles, and relates to a zinc-containing metal organic framework coated manganese dioxide nano composite material, and preparation and application thereof.
Background
With the increasing incidence of cancer worldwide, traditional therapeutic approaches have failed to meet the clinical needs of patients. For example, multidrug resistance in cancer cells is a major cause of chemotherapy failure (H Wang, Z Gao, X Liu, P Agarwal, S ZHao, D W Conroy, G Ji, J Yu, C P Jaronic, Z Liu, et al. targeted production of reactive oxygen species in mitochondria to over cancer drug resistance. Nature Communications 2018,9,562), some cancer cells recognize P-glycoprotein and other related transporters on the plasma membrane. These transporters can recognize and catalyze various anticancer drugs and discharge them out of cancer cells. ATP is indispensable for the function of the transporter. ATP is synthesized by ATP synthase driven by a gradient of the concentration of protons within mitochondria, which is driven by a gradient of ATP concentrationsProduced by Electron Transfer Chain (ETC), Zn2+Tumor resistance (Y Liu, Y Wang, W Zhen, Y Wang, S Zhang, Y ZHao, S Song, Z Wu, H Zhang. Defect modified zinc oxide with an added sensitive reactive oxygen species generation. biomaterials 2020,251,120075.) can be overcome by inhibiting ETC from causing the transporter to malfunction due to lack of ATP supply. Furthermore, sonodynamic therapy (SDT) is increasingly being studied as an emerging noninvasive tumor treatment strategy due to high tumor specificity and low depth of treatment limitations, however, common organic sonosensitizers (e.g., porphyrins and their derivatives) have severe skin photosensitivity, low chemical/biological stability and poor tumor aggregation (D Wang, D-B Cheng, L Ji, L-J Niu, X-H Zhang, Y conn, R-H Cao, L Zhou, F Bai, Z-Y Qiao, et al. Inorganic sonosensitizers such as the commonly used semiconducting titanium dioxide (TiO2) also suffer from poor biodegradability, relatively low ROS quantum yield, poor biocompatibility, etc. (X Wang, X Wang, X Zhong, G Li, Z Yang, Y Gong, Z Liu, L Cheng. V-TiO2 nanospinds with regulating formation microorganism therapy. applied Physics Reviews 2020,7, 041411.).
Thereby adding Zn2+And MnO2The integration of combination therapies for the augmentation of SDT and the inhibition of multidrug resistance under amplified oxidative stress has not been reported. The invention is also based on this.
Disclosure of Invention
The invention aims to provide a zinc-containing metal organic framework coated manganese dioxide nanocomposite and preparation and application thereof, so as to solve the defects that SDT (sodium dodecyl benzene sulfonate) efficiency is low in a hypoxic tumor microenvironment, cancer cells have drug resistance to a chemotherapeutic drug Doxorubicin (DOX) and/or imaging-guided cooperative treatment is difficult to realize in the prior art.
The purpose of the invention can be realized by the following technical scheme:
one of the technical schemes of the invention provides a zinc-containing metal organic framework coated manganese dioxide nano compositeMaterial having a composition consisting of ZIF-90 and MnO deposited on ZIF-902The mesoporous dodecahedron structure is formed.
Further, the average particle size of the composite material is 160-200 nm.
Further, the preparation process of the ZIF-90 nano-particles specifically comprises the following steps:
(A) taking Zn (NO)3)2 4H2Dissolving O in tert-butyl alcohol and deionized water to obtain a solution A;
(B) dissolving PVP and imidazole-2-formaldehyde in glycerol and deionized water, and heating and maintaining to obtain a solution B.
(C) Rapidly adding the solution A into the solution B, violently stirring, keeping at normal temperature, centrifuging, washing and drying to obtain ZIF-90 nano particles;
further, Zn (NO) in the step (A)3)2 4H2The addition amount ratio of the sum of O, tertiary butanol and deionized water (the volume ratio of the two is 1: 0.8-1.2, preferably 1:1) is (350-400) mg: (15-25) mL. .
In the step (B), the addition amount ratio of the PVP, the imidazole-2-formaldehyde, the glycerol and the deionized water (the volume ratio of the PVP to the imidazole-2-formaldehyde to the glycerol to the deionized water is 1: 0.8-1.2, preferably 1:1) is (20-70) mg: (450-550) mg: (15-25) mL.
In the step (B), dispersing the raw materials in glycerol and deionized water, heating to 50-70 ℃, keeping for 30-60 min, dispersing uniformly, and cooling to normal temperature to obtain a solution B.
In the step (C), the process conditions for normal temperature maintenance are as follows: the temperature is 25 ℃, the violent stirring speed is 900rpm/min, and the stirring time is 1-30 min. Meanwhile, the addition amounts of the solution A and the solution B meet the following requirements: zn (NO)3)2.4H2The mass ratio of O to PVP is (350-400): (20-70).
The second technical scheme of the invention provides a preparation method of a zinc-containing metal organic framework coated manganese dioxide nano composite material, which is characterized in that ZIF-90 nano particles are firstly dissolved in deionized water, and KMnO is dropwise added4And stirring the aqueous solution to obtain the target product. In the invention, aldehyde group and KMnO on ZIF-90 nano-particles4Oxidation-reduction reaction is carried out to obtain a catalyst containingThe zinc metal organic framework is coated with the manganese dioxide nano composite material. The material has a porous dodecahedral structure and can load chemotherapeutic drug adriamycin. In addition, ZIF-90 nanoparticles, KMnO4And the addition amount, the temperature and the stirring time of the deionized water are limited, so that MnO with uniform load can be obtained2The dodecahedron structure is over-reacted when the temperature is too high and the maintaining time is more than 2h, so that the dodecahedron structure collapses, and MnO is not more than 0.5h2The conformal coating was not successful.
Further, ZIF-90, KMnO4And the addition amount of deionized water is (5-10) mg: (1-5) mg: (5-10) mL.
Further, ZIF-90 and KMnO4The stirring reaction process is carried out at normal temperature, and the stirring time is 0.5-2 h.
Further, the preparation process of the ZIF-90 nano-particles specifically comprises the following steps:
(1) taking Zn (NO)3)2 4H2Dissolving O in a mixed solvent consisting of tert-butyl alcohol and deionized water to obtain a solution A;
(2) dissolving PVP and imidazole-2-formaldehyde in glycerol and deionized water, and heating to obtain a solution B.
(3) And (3) quickly adding the solution A into the solution B, stirring, keeping at normal temperature, centrifuging, washing and drying to obtain the ZIF-90 nano-particles.
Further, in the step (1), Zn (NO)3)2.4H2The ratio of the addition amount of O to the mixed solvent is (350-400) mg: (15-25) mL;
furthermore, in the step (1), the volume ratio of the tert-butyl alcohol to the deionized water in the mixed solvent is 1: 0.8-1.2, preferably 1: 1.
Furthermore, in the step (2), the mass ratio of PVP to imidazole-2-formaldehyde is (20-70): (450-550).
Furthermore, in the step (2), the volume ratio of the glycerol to the deionized water is 1: 0.8-1.2, preferably 1: 1.
Further, in the step (2), the temperature rise process specifically includes: heating to 50-70 ℃ and keeping for 30-60 min. Because the imidazole-2-formaldehyde can not be uniformly dispersed in the normal temperature environment, most of imidazole-2-formaldehyde ligand can not be reacted in a deposition manner, and the obtained ZIF-90 has overlarge and nonuniform size.
Further, in the step (3), the addition amounts of the solution A and the solution B are as follows: zn (NO)3)2.4H2The mass ratio of O to PVP is (350-400): (20-70).
In the above reaction process, Zn (NO)3)2 4H2The amounts of O, imidazole-2-carbaldehyde, PVP and solvent added are limited to obtain nanoparticles having a particle size of about 160-200nm, and too high a temperature and long stirring time will increase the particle size.
The third technical scheme of the invention provides application of a zinc-containing metal organic framework coated manganese dioxide nano composite material, and the composite material can be used for preparing an anticancer drug release carrier. Preferably, the corresponding anticancer drug may be doxorubicin.
The fourth technical scheme of the invention also provides an application of the zinc-containing metal organic framework coated manganese dioxide nano composite material, and the composite material is used for enhancing the sonodynamic treatment under oxidative stress and overcoming the drug resistance of chemotherapeutic drugs and drugs or reagents for dual sensitive degradation or MR imaging under a weak acid tumor environment and ultrasonic irradiation.
The invention firstly passes Zn2+Complexing with imidazole-2-formaldehyde to prepare ZIF-90 dodecahedral mesoporous structure, and then carrying out redox reaction on MnO based on ZIF-902Coating the outer layer to obtain the zinc-containing metal organic framework coated manganese dioxide nanocomposite. The material has a porous dodecahedral structure, and can provide space for effectively delivering adriamycin (DOX) to tumor tissues; the composite material can release a large amount of DOX and Zn simultaneously under the dual degradation of weak acid environment and ultrasonic irradiation of tumor2+And MnO2。MnO2Catalysis H2O2Can generate O2Overcoming tumor hypoxia environment for enhancing SDT effect, and the generated Mn2+Not only can oxidize GSH in cells, but also can effectively improve the separation of electron holes under the irradiation of US so as to enhance the SDT. In addition, Zn is released2+Can inhibit ETC, and cause dysfunction of plasma membrane efflux pump to overcome multidrug resistance.
Compared with the prior art, the invention has the following advantages:
(1) the zinc-containing metal organic framework coated manganese dioxide nanocomposite material prepared by the invention has a porous structure, and provides a space for effectively delivering adriamycin (DOX) to tumor tissues.
(2) The zinc-containing metal organic framework coated manganese dioxide nanocomposite prepared by the invention has double sensitive degradation effects in a tumor weak acid environment and under ultrasonic irradiation, can effectively release DOX after degradation, and simultaneously releases Zn2+And MnO2。
(3) MnO released after degradation of zinc-containing metal organic framework-coated manganese dioxide nanocomposite prepared by the invention2And H2O2Reaction to form O2Capable of improving hypoxia in the Tumor Microenvironment (TME) to enhance SDT, Mn produced2+Not only can oxidize intracellular GSH to expand oxidative stress, but also can effectively improve the separation of electron holes under the irradiation of US to enhance SDT.
(4) The zinc-containing metal organic framework coated manganese dioxide nanocomposite prepared by the invention has dual-dependency degradation to tumor weak acid environment and under ultrasonic irradiation, so that the toxic and side effects of the nanocomposite on organisms can be reduced.
(5) Zn released after degradation of the zinc-containing metal organic framework coated manganese dioxide nanocomposite material prepared by the invention2+Can inhibit ETC, and cause dysfunction of efflux pump on plasma membrane to overcome DOX resistance of cancer cell, thereby effectively killing cancer cell.
(6) The zinc metal organic framework coated manganese dioxide nanocomposite prepared by the method can realize the effect of the MR imaging guided sonodynamic therapy/chemotherapy synergistic cancer treatment.
Drawings
FIG. 1 is a ZIF-90 and ZIF-90@ MnO in example 1 of the present invention2Scanning electron microscope and transmission electron microscope images of the nanocomposite;
FIG. 2 shows an embodiment of the present inventionZIF-90@ MnO of 12Specific surface area and pore size maps of the nanocomposite;
FIG. 3 is the ZIF-90@ MnO of example 1 of the present invention2An elemental map of the nanocomposite;
FIG. 4 is the ZIF-90@ MnO of example 1 of the present invention2The particle size distribution profile of the nanocomposite;
FIG. 5 is a ZIF-90@ MnO of example 1 of the present invention2ROS detection maps of the nanocomposites;
FIG. 6 is the ZIF-90@ MnO of example 1 of the present invention2A reduction profile of the nanocomposite material to GSH;
FIG. 7 is the ZIF-90@ MnO of example 1 of the present invention2Oxygen generation of the nanocomposite;
FIG. 8 is the ZIF-90@ MnO of example 1 of the present invention2Degradation experimental graph of the nano composite material;
FIG. 9 is the ZIF-90@ MnO of example 1 of the present invention2Zn of nanocomposite2+A release profile;
FIG. 10 is the ZIF-90@ MnO of example 1 of the present invention2UV absorption profile of/DOX nanocomposite;
FIG. 11 is the ZIF-90@ MnO of example 1 of the present invention2Drug release profile of/DOX nanocomposite;
FIG. 12 is the ZIF-90@ MnO of example 1 of the present invention2MRI contrast before and after injection of/DOX nanocomposites into mice.
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 conventional commercially available raw materials or conventional processing techniques in the art are indicated.
Example 1:
preparation of zinc-containing metal-organic framework-coated dioxygenManganese oxide nanocomposite (i.e., ZIF-90@ MnO)2Nanoparticles)
(1) Preparation of ZIF-90 nanoparticles
370mg of Zn (NO) are taken3)2 4H2Dissolving O in 20mL of tert-butyl alcohol and deionized water with the volume ratio of 1:1 to obtain a solution for later use; dissolving 50mg of PVP and 480mg of imidazole-2-formaldehyde in 20mL of glycerol and deionized water with the volume ratio of 1:1, heating to 60 ℃, keeping for 40 minutes, and cooling to obtain a solution B. Rapidly adding the solution B into the solution A under vigorous stirring, maintaining at normal temperature for 10min, centrifuging, washing with methanol for 3 times, and vacuum drying at 60 deg.C for 6h to obtain ZIF-90 nanoparticles with dodecahedral structure shown in FIG. 1 a;
(2) preparation of ZIF-90@ MnO2Nanoparticles
Weighing the obtained 5mg ZIF-90 nano-particles, dissolving in 5mL deionized water, dropwise adding 2mg KMnO4 aqueous solution, stirring at 25 deg.C at normal temperature for 1h, centrifuging, collecting precipitate, and ultrasonic washing with ethanol and deionized water for 3 times respectively to obtain the target product (figure 1 b). Test ZIF-90@ MnO2The adsorption/desorption isotherm of the nanocomposite shows a typical type IV isotherm, which proves the mesoporous characteristics thereof. And the specific surface area and the average pore diameter are 282.93m respectively2 g-1And 6.933nm, indicating ZIF-90@ MnO2The nanocomposite has a mesoporous dodecahedral structure and is suitable for drug loading (fig. 2). ZIF-90@ MnO2The element distribution diagram of the nanocomposite shows the presence of Zn, Mn, O, C, N (FIG. 3), and dynamic light scattering proves ZIF-90@ MnO2The size of the nanocomposite is around 230nm (FIG. 4), which shows that ZIF-90@ MnO is2The nanocomposite material is successfully prepared and has uniform size.
Example 2
ZIF-90@MnO2Determination of ROS in ultrasonic condition of nano composite particle
The ZIF-90 and ZIF-90@ MnO residues obtained in example 1 were taken2(200. mu.g/mL) and deionized water 1mL each were placed in 3 10mL centrifuge tubes, and H was added separately2O2(870. mu.L, 100mM) + DPBF (130. mu.L, 1 mg/mL). Repeating the above steps to obtain a group of identical (3 centrifuge tubes), and allowing the two groups to pass throughAnd (3) treating in the presence and absence of sound, taking out supernatant through centrifugation, measuring an absorption spectrum of the supernatant by using an ultraviolet-visible spectrophotometer, and monitoring the attenuation trend at 652nm at different time points. The results are shown in FIG. 5, ZIF-90@ MnO2+H2O2The attenuation trend of the + US group is strongest, indicating ZIF-90@ MnO2The nanocomposite can generate a large amount of ROS through ultrasonic action.
Example 3
ZIF-90@MnO2Consumption experiment of nanocomposite on GSH
ZIF-90, ZIF-90@ MnO obtained in example 12Dispersing the nano composite particles in deionized water, and adding PBS (pH 7.4), ZIF-90@ MnO and MnO into reduced GSH (1mL, 2M) respectively2(200μg/mL)、H2O2(200mM) 1mL each, reacting for 30min, centrifuging to collect the supernatant, adding 10. mu.L of DTNB (DMSO,100mM), shaking in a shaker for 30min, and detecting the absorbance spectrum at 410nm with UV. The results are shown in FIG. 6, ZIF-90@ MnO2The result is the same as that of the positive control group, which shows that ZIF-90@ MnO2Capable of reducing GSH.
Example 4
ZIF-90@MnO2Oxygen generation detection of nanocomposites
Taking ZIF-90@ MnO obtained in example 12(0 or 200. mu.g/mL), PBS (pH 6.5,2mL) and H2O2(1mL,100mM) were placed in 50mL centrifuge tubes, respectively, and then stirred at 37 ℃ for 10 minutes. The oxygen content was measured with a dissolved oxygen meter. The results are shown in FIG. 7, ZIF-90@ MnO2Can catalyze H2O2A large amount of oxygen was generated, indicating ZIF-90@ MnO2The nano composite material can relieve the hypoxia of a tumor microenvironment.
Example 5
ZIF-90@MnO2Degradation properties of nanocomposites
Taking ZIF-90@ MnO obtained in example 12Dispersed in PBS solution (pH 6.5 and 7.4) and stirred in a shaker for 8h, respectively, with or without sonication. Transmission electron microscope pair ZIF-90@ MnO2Was evaluated. The results are shown in FIG. 8, ZIF-90@ MnO at pH 6.52Gradually crushing, and under the combined action of pH 6.5 plus US, ZIF-90@ MnO2More remarkable degradation is shown, which indicates that ZIF-90@ MnO is2Can be degraded in tumor environment and US.
Example 6
ZIF-90@MnO2Zn released after degradation of nanocomposite2+Testing
Taking ZIF-90@ MnO obtained in example 12Dispersed in PBS solution of pH5.0, 6.5, 7.4, and shaken at 200 rpm/min. Centrifuging at 0,2, 4, 8, 12, 24, 48, 36 and 72h to obtain supernatant, and measuring Zn by inductively coupled plasma spectrometry (ICP-OES)2+The amount of (a) released. The results are shown in FIG. 9, ZIF-90@ MnO at pH 6.52Over 50% of Zn is released2+And ZIF-90@ MnO at pH5.0298% of Zn is released2+Indicates Zn2+Can be released in large amount for inhibiting multidrug resistance of cancer cells.
Example 7
(1) Drug loading
4mg of ZIF-90@ MnO as obtained in example 1 was taken2The nanocomposite particles were mixed with 1mL of 1mg/mL DOX and shaken in a shaker at room temperature for 24 h. After centrifugation, the centrifuged product was collected and measured for its absorption peak in the near infrared region by UV-visible spectrophotometer, and the result is shown in FIG. 10, ZIF-90@ MnO2The nano composite particle has obvious DOX absorption peak at 480 nm.
(2) Drug delivery
Taking the prepared 4mg ZIF-90@ MnO2the/DOX was dispersed in 5mL of PBS (pH 6.5 and 7.4), respectively, and the supernatant was collected for UV measurement of the amount of drug released in the presence or absence of sonication for a predetermined period of time. The results are shown in FIG. 11, ZIF-90@ MnO2The maximum percentage of DOX releasable under pH 6.5+ US irradiation indicates ZIF-90@ MnO2the/DOX nano composite material can release the maximum amount of chemotherapeutic drug DOX under the dual stimulation of tumor environment and US irradiation.
Example 8
In vivo intravenous injection of ZIF-90@ MnO in HeLa tumor-bearing mice2a/DOX nanocomposite (200. mu.L, 2mg/mL),t1-weighted MRI in vivo, the results are shown in FIG. 12, injection of ZIF-90@ MnO2The tumor area of the mouse after the/DOX nano composite material becomes bright obviously, which shows that ZIF-90@ MnO2the/DOX nano composite material has the function of guiding nuclear magnetic imaging.
Comparative example 1:
compared with example 1, the method is mostly the same except that MnO in step (2) is omitted2The load of (2). As shown in FIG. 4, the synthesized ZIF-90@ MnO2The ROS generation amount of the product is much stronger than that of ZIF-90, and the ZIF-90@ MnO is proved2The sound power treatment effect is better. As shown in FIG. 5, ZIF-90@ MnO had no significant effect on GSH compared to ZIF-90 which had the same negative control effect2GSH can be consumed, and MnO is shown in FIG. 62Contribute to the generation of oxygen, and all show that MnO obtained in example 12The nanocomposite material can amplify oxidative stress for enhancing sonodynamic therapeutic effects.
Example 8:
multifunctional ZIF-90@ MnO2The preparation method of the nano composite material comprises the following steps:
(1) preparation of ZIF-90 nanoparticles
350mg of Zn (NO) are taken3)2 4H2Dissolving O in 15mL of tert-butyl alcohol and deionized water with the volume ratio of 1:1 to obtain a solution for later use; dissolving 20mg of PVP and 450mg of imidazole-2-formaldehyde in 15mL of glycerol and deionized water with the volume ratio of 1:1, heating to 50 ℃, keeping for 60 minutes, and cooling to obtain a solution B. Rapidly adding the solution B into the solution A under vigorous stirring, keeping the temperature at normal temperature for 1min, centrifuging, washing with methanol for 3 times, and vacuum drying at 60 ℃ for 6h to obtain ZIF-90 nanoparticles;
(2) preparation of ZIF-90@ MnO2Nanoparticles
Weighing the obtained 5mg ZIF-90 nano-particles, dissolving in 5mL deionized water, and dropwise adding 1mg KMnO4Stirring the aqueous solution at the normal temperature of 25 ℃ for 2h, centrifuging, taking the precipitate, and respectively ultrasonically washing the precipitate for 3 times by using ethanol and deionized water to obtain the target product.
Example 9:
multifunctional ZIF-90@ MnO2Preparation method of nano composite materialThe method comprises the following steps:
(1) preparation of ZIF-90 nanoparticles
400mg of Zn (NO) are taken3)2 4H2Dissolving O in 25mL of tert-butyl alcohol and deionized water with the volume ratio of 1:1 to obtain a solution for later use; 70mg of PVP and 550mg of imidazole-2-formaldehyde are dissolved in 25mL of glycerol and deionized water with the volume ratio of 1:1, the temperature is raised to 70 ℃, the mixture is kept for 30 minutes and then cooled, and solution B is obtained. Rapidly adding the solution B into the solution A under vigorous stirring, keeping the temperature at normal temperature for 10min, centrifuging, washing with methanol for 3 times, and vacuum-drying at 60 ℃ for 6h to obtain ZIF-90 nanoparticles;
(2) preparation of ZIF-90@ MnO2Nanoparticles
Weighing the obtained 10mg ZIF-90 nano-particles, dissolving in 5mL deionized water, and dropwise adding 5mg KMnO4Stirring the aqueous solution at the normal temperature of 25 ℃ for 30min, centrifuging, taking the precipitate, and respectively ultrasonically washing the precipitate for 3 times by using ethanol and deionized water to obtain the target product.
Example 10:
multifunctional ZIF-90@ MnO2The preparation method of the nano composite material comprises the following steps:
(1) preparation of ZIF-90 nanoparticles
350mg of Zn (NO) are taken3)2 4H2Dissolving O in 15mL of tert-butyl alcohol and deionized water with the volume ratio of 1:1 to obtain a solution for later use; dissolving 50mg of PVP and 550mg of imidazole-2-formaldehyde in 25mL of glycerol and deionized water with the volume ratio of 1:1, heating to 70 ℃, keeping for 30 minutes, and cooling to obtain a solution B. Rapidly adding the solution B into the solution A under vigorous stirring, keeping the temperature at normal temperature for 20min, centrifuging, washing with methanol for 3 times, and vacuum drying at 60 ℃ for 6h to obtain ZIF-90 nanoparticles;
(2) preparation of ZIF-90@ MnO2Nanoparticles
Weighing the obtained 5mg ZIF-90 nano-particles, dissolving in 10mL deionized water, and dropwise adding 1mg KMnO4Stirring the aqueous solution at the normal temperature of 25 ℃ for 2h, centrifuging, taking the precipitate, and respectively ultrasonically washing the precipitate for 3 times by using ethanol and deionized water to obtain the target product.
Example 11:
multifunctional ZIF-90@ MnO2The preparation method of the nano composite material comprises the following steps:
(1) preparation of ZIF-90 nanoparticles
400mg of Zn (NO) are taken3)2 4H2Dissolving O in 25mL of tert-butyl alcohol and deionized water with the volume ratio of 1:1 to obtain a solution for later use; dissolving 50mg of PVP and 450mg of imidazole-2-formaldehyde in 15mL of glycerol and deionized water with the volume ratio of 1:1, heating to 50 ℃, keeping for 60 minutes, and cooling to obtain a solution B. Rapidly adding the solution B into the solution A under vigorous stirring, keeping the temperature at normal temperature for 20min, centrifuging, washing with methanol for 3 times, and vacuum drying at 60 ℃ for 6h to obtain ZIF-90 nanoparticles;
(2) preparation of ZIF-90@ MnO2Nanoparticles
Weighing the obtained 5mg ZIF-90 nano-particles, dissolving in 5mL deionized water, and dropwise adding 1mg KMnO4Stirring the aqueous solution at the normal temperature of 25 ℃ for 2h, centrifuging, taking the precipitate, and respectively ultrasonically washing the precipitate for 3 times by using ethanol and deionized water to obtain the target product.
Example 12
Multifunctional ZIF-90@ MnO2The preparation method of the nano composite material comprises the following steps:
(1) preparation of ZIF-90 nanoparticles
370mg of Zn (NO) are taken3)2 4H2Dissolving O in 20mL of tert-butyl alcohol and deionized water with the volume ratio of 1:1 to obtain a solution for later use; dissolving 50mg of PVP and 480mg of imidazole-2-formaldehyde in 20mL of glycerol and deionized water in a volume ratio of 1:1, heating to 70 ℃, keeping for 40 minutes, and cooling to obtain a solution B. Rapidly adding the solution B into the solution A under vigorous stirring, keeping the temperature at normal temperature for 10min, centrifuging, washing with methanol for 3 times, and vacuum-drying at 60 ℃ for 6h to obtain ZIF-90 nanoparticles;
(2) preparation of ZIF-90@ MnO2Nanoparticles
Weighing the obtained 10mg ZIF-90 nano-particles, dissolving in 10mL deionized water, and dropwise adding 1mg KMnO4Stirring the aqueous solution at the normal temperature of 25 ℃ for 2h, centrifuging, taking the precipitate, and respectively ultrasonically washing the precipitate for 3 times by using ethanol and deionized water to obtain the target product.
Example 13
Multifunctional ZIF-90@ MnO2The preparation method of the nano composite material comprises the following steps:
(1) preparation of ZIF-90 nanoparticles
370mg of Zn (NO) are taken3)2 4H2Dissolving O in 20mL of tert-butyl alcohol and deionized water with the volume ratio of 1:1 to obtain a solution for later use; dissolving 50mg of PVP and 480mg of imidazole-2-formaldehyde in 20mL of glycerol and deionized water in a volume ratio of 1:1, heating to 70 ℃, keeping for 40 minutes, and cooling to obtain a solution B. Rapidly adding the solution B into the solution A under vigorous stirring, keeping the temperature at normal temperature for 10min, centrifuging, washing with methanol for 3 times, and vacuum-drying at 60 ℃ for 6h to obtain ZIF-90 nanoparticles;
(2) preparation of ZIF-90@ MnO2Nanoparticles
Weighing the obtained 5mg ZIF-90 nano-particles, dissolving in 5mL deionized water, and dropwise adding 5mg KMnO4Stirring the aqueous solution at the normal temperature of 25 ℃ for 30min, centrifuging, taking the precipitate, and respectively ultrasonically washing the precipitate for 3 times by using ethanol and deionized water to obtain the target product.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. 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 improvements and modifications within the scope of the present invention based on the disclosure of the present invention.

Claims (10)

1. A zinc-containing metal organic framework coated manganese dioxide nanocomposite is characterized by comprising ZIF-90 and MnO deposited on the ZIF-902The mesoporous dodecahedron structure is formed.
2. The zinc-containing metal-organic framework-coated manganese dioxide nanocomposite material as claimed in claim 1, wherein the average particle size of the composite material is 160-200 nm.
3. The method for preparing the zinc-containing metal organic framework coated manganese dioxide nanocomposite material as claimed in claim 1 or 2, wherein ZIF-90 nanoparticles are dissolved in deionized water, and KMnO is added dropwise4And stirring the aqueous solution to obtain the target product.
4. The preparation method of the zinc-containing metal-organic framework coated manganese dioxide nanocomposite material according to claim 3, wherein ZIF-90 and KMnO are adopted4And the addition amount of deionized water is (5-10) mg: (1-5) mg: (5-10) mL.
5. The preparation method of the zinc-containing metal organic framework coated manganese dioxide nanocomposite material according to claim 3, wherein stirring is performed at normal temperature for 0.5-2 h.
6. The preparation method of the zinc-containing metal organic framework coated manganese dioxide nanocomposite material according to claim 3, wherein the preparation process of the ZIF-90 nanoparticles comprises the following specific steps:
(1) taking Zn (NO)3)2 4H2Dissolving O in a mixed solvent consisting of tert-butyl alcohol and deionized water to obtain a solution A;
(2) dissolving PVP and imidazole-2-formaldehyde in glycerol and deionized water, and heating to obtain a solution B;
(3) and (3) quickly adding the solution A into the solution B, stirring, keeping at normal temperature, centrifuging, washing and drying to obtain the ZIF-90 nano-particles.
7. The method for preparing a zinc-containing metal-organic framework coated manganese dioxide nanocomposite material according to claim 6, wherein in the step (1), Zn (NO) is added3)2·4H2The ratio of the addition amount of O to the mixed solvent is (350-400) mg: (15-25) mL;
in the mixed solvent, the volume ratio of the tert-butyl alcohol to the deionized water is 1: 0.8-1.2.
8. The preparation method of the zinc-containing metal-organic framework coated manganese dioxide nanocomposite material according to claim 6, wherein in the step (2), the mass ratio of PVP to imidazole-2-formaldehyde is (20-70): (450-550);
the volume ratio of the glycerol to the deionized water is 1: 0.8-1.2;
the temperature rise process specifically comprises the following steps: heating to 50-70 ℃ and keeping for 30-60 min.
9. The preparation method of the zinc-containing metal-organic framework coated manganese dioxide nanocomposite material according to claim 6, wherein in the step (3), the addition amounts of the solution A and the solution B are as follows: zn (NO)3)2·4H2The mass ratio of O to PVP is (350-400): (20-70).
10. Use of a zinc-containing metal-organic framework coated manganese dioxide nanocomposite material according to claim 1 or 2 for the preparation of an anticancer drug release carrier or a medicament for enhanced sonodynamic therapy under oxidative stress, dual sensitive degradation in tumor mild acid environments and ultrasound irradiation or MR imaging.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114671871A (en) * 2022-03-25 2022-06-28 中山大学 Metal-organic cage nano composite drug-loading system and preparation method and application thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017157063A1 (en) * 2016-03-16 2017-09-21 深圳大学 Nanocarrier-drug composite for treating cancer and manufacturing method thereof
US10561747B1 (en) * 2018-11-26 2020-02-18 King Saud University Multifunctional cancer targeting nanoparticles
CN111253581A (en) * 2020-01-19 2020-06-09 浙江大学 Metal organic framework material for enhancing combination of chemical power therapy and hunger therapy, preparation method and application
CN113174141A (en) * 2021-04-09 2021-07-27 中国石油大学(华东) ZIF-8/MnO2Preparation method and application of composite material

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017157063A1 (en) * 2016-03-16 2017-09-21 深圳大学 Nanocarrier-drug composite for treating cancer and manufacturing method thereof
US10561747B1 (en) * 2018-11-26 2020-02-18 King Saud University Multifunctional cancer targeting nanoparticles
CN111253581A (en) * 2020-01-19 2020-06-09 浙江大学 Metal organic framework material for enhancing combination of chemical power therapy and hunger therapy, preparation method and application
CN113174141A (en) * 2021-04-09 2021-07-27 中国石油大学(华东) ZIF-8/MnO2Preparation method and application of composite material

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114671871A (en) * 2022-03-25 2022-06-28 中山大学 Metal-organic cage nano composite drug-loading system and preparation method and application thereof
CN114671871B (en) * 2022-03-25 2023-07-14 中山大学 Metal-organic cage nano composite drug-carrying system and preparation method and application thereof

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