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Gene and chemical small molecule co-delivery system and application in tumor treatment

A technology for co-delivery and treatment of drugs, applied in gene therapy, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc., to achieve the effect of enhancing homing ability, restoring curative effect, and preventing leakage

Active Publication Date: 2020-07-24
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Colon cancer, a typical "cold" cancer in bioinformatics, was found to overexpress CD47 but did not respond satisfactorily to its corresponding immune checkpoint blockade (ICB) clinically

Method used

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  • Gene and chemical small molecule co-delivery system and application in tumor treatment
  • Gene and chemical small molecule co-delivery system and application in tumor treatment
  • Gene and chemical small molecule co-delivery system and application in tumor treatment

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Experimental program
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preparation example Construction

[0045] In addition, the present invention also provides a preparation method of the co-delivery system of the above-mentioned antineoplastic drugs, the preparation method comprising the following steps: preparing the encapsulating ZIF-8-based GEM and siIDO co-loaded nanocages (GSZ ), adding KMnO to the GSZ solution 4 Stir evenly to obtain a GSZM solution, add aCD-47 into the GSZM solution and stir evenly to obtain GSZMA nanoparticles.

[0046] In a typical implementation of the present invention, a specific preparation method is provided, and the steps of the preparation method are as follows:

[0047] (1) Zinc nitrate was dissolved in ultrapure water, and then added to the GEM and siIDO solution under stirring. Subsequently, the mixed solution was added dropwise to the 2-methylimidazole solution by stirring; stirred for 10 min at room temperature in the dark, then GSZ was separated by centrifugation and washed three times with ultrapure water; the final product was finally c...

Embodiment 1

[0063] (1) Dissolve 47.4mg of zinc nitrate in 5mL of ultrapure water, then add GEM (2mL, 40mg mL) under stirring -1 ) and siIDO (10 μL, 50 μM) solution. Subsequently, the mixed solution was added dropwise to 2-methylimidazole solution (5 mL, 65.7 mg mL -1 )middle. After stirring for 10 min at room temperature in the dark, GSZ was prepared and then isolated by centrifugation, washed three times with ultrapure water, and the final product was collected by vacuum drying.

[0064] (2) KMnO 4 Solution (5mL, 0.2mgml -1 ) was added dropwise to GSZ (3mL, 1mgml -1 ) solution and stirred for 10 min, then collected nanoparticles with a centrifuge and washed three times with ultrapure water. aCD-47 (50μL, 5mg mL -1 ) slowly drop into GSZM solution (1mL, 2mg mL -1 ), stirred for 5 min to obtain GSZMA nanoparticles, which were redispersed in PBS buffer after centrifugation.

[0065] The morphology of the GSZMA nanosheets prepared in this example is characterized, and the TEM spectru...

Embodiment 2

[0066] Example 2 Cytotoxicity test evaluation

[0067] The in vitro cytotoxicity of drug-loaded preparations was determined by MTT method, and CT26 tumor cells were divided into 5×10 3 Cells / well density were seeded in 96-well plates and cultured until reaching 80% confluency. Replace the cell culture medium with a series of medium with different concentrations and different formulations for 48 hours, remove the medium, and use 100 μL MTT reagent (0.5 mg mL -1 ) incubate for 4 hours, remove the MTT solution, add 150 μL DMSO to dissolve the metabolically active cells, let stand on a shake flask at 37° C. for 10 minutes, and measure the absorbance with a microplate reader at a wavelength of 490 nm. The result is as image 3 As shown, from the measurement results, GEM, GZ, GSZ, GSZM and GSZMP all have good killing effect on CT26 cells, but the killing effect of GSZMA nanocomposite on CT26 cells is stronger than that of free GEM, indicating that the composite material has a bett...

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Abstract

The invention specifically relates to a gene and chemical small molecule co-delivery system and an application in tumor treatment. In the drug co-delivery system, small interference RNA targeting indoleamine 2,3-dioxygenase-1, and gemcitabine are loaded in a 2-methylimidazole zinc metal-organic framework nano-cage in a combined manner for the first time to relieve immunosuppression related to regulatory T cells and myeloid-derived suppressor cells; then a mineralization substance which can produce oxygen is mineralized on the nano-carrier surface to reduce immunosuppression of M2 macrophage; and after a therapeutic ICB antibody is modified on the mineralized shell surface, a multifunctional nano-regulator is constructed. The multifunctional nano-regulator integrates multiple efficacies, stimulates a "hot" tumor microenvironment, and greatly enhances ICB treatment of "cold" malignant tumors.

Description

technical field [0001] The invention belongs to the technical field of anti-tumor drug delivery, and in particular relates to a metal-organic nanocomposite for co-delivery of genes and small chemical molecules and its application in the preparation of anti-tumor drugs. 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] Currently, chemotherapy remains the basis of modern cancer treatment. Specialized chemotherapy, such as oxaliplatin (OXA), can induce true immunogenic cell death (ICD) in cancer cells. ICD-induced immunogenicity can promote intertumoral infiltration of cytotoxic T lymphocytes (CTLs) and accelerate tumor regression. However, in colon cancer and glioma, there ...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/52A61K31/7068A61K31/7088A61K48/00A61P35/00A61P35/04B82Y5/00B82Y30/00B82Y40/00A61K45/06
CPCA61K9/0019A61K31/7068A61K31/7088A61K45/06A61K48/0033A61K47/52A61K47/6949A61P35/00A61P35/04B82Y5/00B82Y30/00B82Y40/00A61K2300/00
Inventor 姜新义陈晨唐春伟张晶
Owner SHANDONG UNIV
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