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Preparation method of long-circulation multifunctional metal organic framework nano preparation

A metal-organic framework and nano-formulation technology, applied in the field of biomedicine, can solve the problems of inability to specifically recognize and take up tumor cells, the complexity of tumor microenvironment, difficult drug release, etc., to solve the problem of drug loading and excellent biocompatibility. The effect of high stability and high encapsulation rate

Pending Publication Date: 2022-07-12
SHANDONG FIRST MEDICAL UNIV & SHANDONG ACADEMY OF MEDICAL SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although constructing stimuli-responsive nanocarriers can increase tumor-specific drug release, due to the heterogeneity of tumors, the complexity and instability of the tumor microenvironment, it is difficult to achieve precise control of drug release at the target site. Therefore, the existing ZIF -8 Poor targeting, incapable of specific recognition and uptake of tumor cells

Method used

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  • Preparation method of long-circulation multifunctional metal organic framework nano preparation
  • Preparation method of long-circulation multifunctional metal organic framework nano preparation
  • Preparation method of long-circulation multifunctional metal organic framework nano preparation

Examples

Experimental program
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Effect test

Embodiment 1

[0053] The preparation method of long-circulating multifunctional metal-organic framework nano-formulation is as follows:

[0054] (1) Add ferric chloride (FeCl) dropwise to the gallic acid (GA) solution under vigorous stirring. 3 ) and polyvinylpyrrolidone (PVP) for 12 h stirring reaction; gallic acid (GA) and ferric chloride (FeCl) 3 ), the molar ratio of mineralizer is 1:2:5; the molecular weight of polyvinylpyrrolidone (PVP) is 40kD;

[0055] (2) After the reaction, the solution was dialyzed and then freeze-dried to obtain GA / Fe nanocomposite; the TEM image of GA / Fe(III) nanocomposite is shown in figure 1 shown, through figure 1 It can be seen that the particle size of the GA / Fe(III) nanocomposite is uniform, and the average particle size is 20 nm;

[0056] (3) 10 mg of eight-arm polyethylene glycol (8-arm-PEG-OH) with a molecular weight of 40 kDa, 1 mg of glucose oxidase (GOx), 1 mg of doxorubicin (Dox), 50 mg of GA / Fe The nanocomposite and 2 mL of 2-methylimidazole...

experiment example 1

[0075] Experimental Example 1: Uptake of Nanomedicine by 4T1 Cells

[0076] 4T1 cells cultured to log phase (density 80-90%) were digested with 0.25% trypsin, 5 × 10 per well 3 The density of the cells was seeded in a four-cell confocal dish, and cultured in the incubator for 24 h until the cells adhered (37 °C, 5% CO). 2 ). The medium was aspirated, and PBS was added to wash the 24-well culture plate 3 times, and then cultured overnight. 4T1 cells were incubated with 4T1 cells containing 31.2 mg / mL Dox&GGF@ZIF-8 (Comparative Example 4) and Dox&GGF@ZIF-8@HA (Example 1). After culturing for 8 hours, cells were fixed with paraformaldehyde, nuclei were stained with Hoechst 33342, and membranes were stained with WGA633, and then the dye solution was removed, and anti-fluorescence quencher was added for preservation. The samples were observed under a confocal microscope. The result is as Figure 4 shown, through Figure 4 It can be seen that the tumor cells that can be specific...

experiment example 2

[0077] Experimental Example 2: The effect of nanomedicine on the proliferation of 4T1 cells

[0078] Cultivate 4T1 cells to grow to log phase, digest, collect and add to 96-well cell culture plate (3 × 10 4 cells / mL), and cultured for 24 h until the cells adhered. Different concentrations of ZIF-8 (Comparative Example 3), Dox@ZIF-8 (Comparative Example 2), GGF@ZIF-8 (Comparative Example 1), Dox&GGF@ZIF-8 (Comparative Example 4) and Dox&GGF@ZIF were added respectively -8@HA (Example 1), PBS was used as a blank control, and cultured in the incubator for 24 h. Take out the 96-well plate, add 20 μL of MTT solution (5 mg / mL) to each well under sterile conditions, and continue to incubate for 4 h. After discarding the supernatant, add 150 μL of DMSO to each well to dissolve the formazan particles. After complete dissolution, use a microplate reader to detect the absorbance value (OD570) at 570 nm. Cell viability assay results such as Figure 5 As shown, the results show that t...

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Abstract

The invention relates to a preparation method of a long-circulation multifunctional metal organic framework nano-preparation, which comprises the following steps: preparing a GA / Fe nano-composite with moderate particle size by taking PVP (Polyvinyl Pyrrolidone) as a mineralizer, and then obtaining white nano-particles; white nano-particles are dissolved and soaked in a hyaluronic acid solution for incubation, and the multifunctional metal organic framework nano-preparation is prepared; the preparation has excellent biocompatibility, tumor targeting ability, bimodal imaging function and combined CDT / hunger therapy / chemotherapy ability, in-situ imaging and treatment of tumors can be realized at the same time, stealth can be realized in vivo due to doping of polyethylene glycol, long circulation is realized, the preparation has good targeting ability, and the preparation has good application prospects. A PVA / Fe nano-composite based on polyvinylpyrrolidone is packaged, so that the preparation simultaneously realizes a T2 imaging effect based on Fe < 3 + >, the spatial position of a tumor can be accurately obtained, and gallic acid can reduce Fe < 3 + > generated by a Fenton reaction and accelerate the Fenton reaction to generate. OH to effectively kill tumor cells; good application prospects are realized in tumor treatment.

Description

technical field [0001] The invention relates to a preparation method of a long-circulating multifunctional metal-organic framework nano-formulation, belonging to the technical field of biomedicine. Background technique [0002] With the deterioration of the environment and changes in lifestyle, the incidence of cancer is increasing year by year, and the number of newly diagnosed cancer cases is expected to rise by about 70% in the next 20 years. Therefore, malignant tumors are still a difficult problem faced by all human beings, and safe and effective treatment methods still need to be developed and applied. [0003] In recent years, chemodynamic therapy (CDT) has received extensive attention as an emerging cancer treatment strategy. endogenous hydrogen peroxide (H 2 O 2 ) through the Fenton reaction mediated by metal ions (mainly Fe(III) and Fe(II)) can be converted into cytotoxic hydroxyl radicals ( OH), promoting the accumulation of intracellular lipid peroxides, and f...

Claims

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Application Information

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IPC IPC(8): A61K9/52A61K38/44A61K47/69A61K47/60A61K49/18A61P35/00C08G83/00B82Y5/00B82Y30/00B82Y40/00A61K31/192A61K31/704A61K33/26
CPCA61K38/443A61K31/704A61K31/192A61K33/26A61K9/5161A61K47/6949A61K47/60C12Y101/03004A61P35/00A61K49/1863A61K49/189C08G83/008B82Y5/00B82Y30/00B82Y40/00A61K2300/00
Inventor 付潇吴海威张东升侯亚丽
Owner SHANDONG FIRST MEDICAL UNIV & SHANDONG ACADEMY OF MEDICAL SCI
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