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Metal organic framework drug-loaded nano system based on small molecule drug

A metal-organic framework and drug-loaded nanotechnology, applied in the field of medicine, can solve the problems of GSDME expression silencing, and achieve strong cytotoxicity, enhanced immune effects, and good anti-tumor effects

Active Publication Date: 2021-06-04
SHANDONG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] In order to solve the problem that the DNA methylation of the promoter region in the prior art leads to the expression silencing of GSDME, the present invention proposes a metal-organic framework drug-loaded nanosystem based on small molecule drugs and its preparation method and application

Method used

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  • Metal organic framework drug-loaded nano system based on small molecule drug
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  • Metal organic framework drug-loaded nano system based on small molecule drug

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preparation example Construction

[0054] In one or more embodiments of the present invention, taking MIT, HYD, and ZIF-8 metal-organic frameworks as examples, the preparation method includes: dissolving MIT, HYD in water, and adding them dropwise to zinc nitrate hexahydrate (ZnNO 3 ·6H 2 O) In the aqueous solution, the above mixed solution was added dropwise to the 2-MIM aqueous solution under stirring conditions; the suspension formed above was centrifuged, washed with water, and dried to obtain a blue solid, namely (M+H)@ZIF-8;

[0055] (M+H)@ZIF-8 was evenly dispersed in the aqueous solution of HA, stirred at room temperature, the formed suspension was centrifuged, washed with water, and dried to obtain a blue solid, which is a tumor-targeting active tumor based on MIT and HYD. Metal-organic framework drug delivery system (M+H)@ZIF / HA.

[0056] The third aspect of the present invention provides an immune-enhancing drug or an anti-tumor drug, including a metal-organic framework drug-loaded nanosystem based ...

Embodiment 1

[0062] Example 1: A metal organic framework drug delivery system with active tumor targeting function based on mitoxantrone (MIT) and hydralazine (HYD) was prepared as an intravenous preparation.

[0063] Precisely weigh 30mg of MIT and 10mg of HYD with an analytical balance, dissolve them in 2mL of water, and drop in 200mg / mL of ZnNO 3 ·6H 2 O aqueous solution, and then drop the above suspension into 2g / mL 2-MIM aqueous solution under the condition of stirring, the drug-loaded ZIF nanoparticles spontaneously formed, the suspension was centrifuged, washed with water, the supernatant was discarded, and vacuum-dried to obtain blue Color solid (M+H)@ZIF-8.

[0064] (M+H)@ZIF-8 with a concentration of 2mg / mL was uniformly dispersed in a 10mg / mL hyaluronic acid aqueous solution and stirred at room temperature for 36h; the resulting suspension was centrifuged, washed with water, and dried to obtain a blue solid. It is dispersed uniformly in water by ultrasonic to obtain an intrave...

Embodiment 2

[0065] Example 2: Morphological observation of (M+H)@ZIF / HA nanoaggregates.

[0066] Take 20 μL (M+H)@ZIF / HA nano-aggregate suspension, drop it on the carbon-coated copper mesh, absorb the excess liquid with filter paper, dry it at room temperature, and observe it under a transmission electron microscope (M+H)@ZIF / HA Nanoaggregate Morphology. Electron microscope photos such as figure 1 , the results show that (M+H)@ZIF / HA can be dispersed in water into a relatively round nanoparticle structure with a diameter of about 100-200nm, with uniform shape and good dispersion. The nanoparticle size is suitable for intravenous injection and meets the requirements of Enhanced penetration and retention (EPR) effect on particle size requirements. The preparation process of nanoparticles does not require the addition of organic solvents, surfactants, and heating, and the reaction is simpler and faster.

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Abstract

The invention provides a preparation method and application of a metal organic framework drug-loaded nano system based on a small molecule drug, MIT and HYD are jointly loaded in pores of a metal organic framework ZIF-8 through a simple and rapid method to prepare nano particles, and active targeting HA modification of tumor cells is realized. The problems of poor stability of MIT and HYD and co-delivery of MIT and HYD are solved, and the immune efficacy of chemotherapeutic drugs is enhanced. The (M+H) (at) ZIF / HA intravenous injection preparation is low in toxicity, good in safety, high in tumor cell toxicity and obvious in solid tumor inhibition effect.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a metal-organic framework drug-carrying nano system based on small-molecule drugs and its preparation method and application. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] In recent years, more than 10 million new cancer cases have been diagnosed each year, and in 2018, approximately 9.6 million patients died from the disease. Over the next two decades, this number is expected to grow by approximately 70%. Tumor immunotherapy is a new treatment method developed on the basis of tumor immunology, which is characterized by regulating the body's immune defense mechanism to exe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/36A61K47/22A61K31/136A61K31/502A61P35/00
CPCA61K47/36A61K47/22A61K31/136A61K31/502A61P35/00A61K2300/00
Inventor 栾玉霞周诗瑶
Owner SHANDONG UNIV
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