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Nanometer drug administration system based on metal organic framework, and preparation method and application of nanometer drug administration system

A metal-organic framework and drug delivery system technology, applied in the field of medicine, can solve the problems of tryptophan depletion, immune escape, reduced anti-tumor immune efficacy, etc., and achieve the effects of efficient aggregation, easy storage and transportation, and good anti-tumor effect.

Active Publication Date: 2019-12-03
SHANDONG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In the process of tumor immunity, the highly expressed indoleamine 2,3-dioxygenase (IDO) in antigen-presenting cells can catalyze the degradation of tryptophan into immunosuppressive kynurenine, and the high expression of IDO will lead to Depletion of amino acid, thereby inhibiting the proliferation and function of effector T cells and inducing the generation of immunosuppressive regulatory T cells, resulting in immune escape and reducing the efficacy of anti-tumor immunity

Method used

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  • Nanometer drug administration system based on metal organic framework, and preparation method and application of nanometer drug administration system
  • Nanometer drug administration system based on metal organic framework, and preparation method and application of nanometer drug administration system
  • Nanometer drug administration system based on metal organic framework, and preparation method and application of nanometer drug administration system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Example 1: A novel indocyanine green (IR820) based metal organic framework drug delivery system with active tumor targeting function was prepared as an intravenous formulation.

[0067] Accurately weigh about 32mg of IR820, dissolve it in 4mL of water, add 1mL of Zn(NO 3 ) 2 ·6H 2 O aqueous solution (125mg / mL), and then drop the above suspension into 10mL of 2-methylimidazole aqueous solution (125mg / mL) under stirring conditions, the drug-loaded MOF nanoparticles formed spontaneously, and the suspension was centrifuged and washed with water. , the supernatant was discarded, and vacuum-dried to obtain a green solid IR820@ZIF-8.

[0068] Uniformly disperse IR820@ZIF-8 in 30mL 3mg / mL hyaluronic acid (HA) aqueous solution and stir at room temperature for 48h; centrifuge the formed suspension, wash with water, and dry to obtain a green solid, which is evenly dispersed in water by ultrasonic to obtain vein Injection formulation, denoted as HA / IR820@ZIF-8 nanoaggregate. Th...

Embodiment 2

[0071] Example 2: A metal organic framework drug delivery system based on imiquimod (R837) and 1-methyltryptophan (1MT) with the active targeting function of antigen-presenting cells was prepared as an intravenous preparation.

[0072] Accurately weigh about 5 mg of R837, dissolve it in 2 mL of DMSO, and add 1 mL of Zn(NO 3 ) 2 ·6H 2 O aqueous solution (62.5mg / mL), accurately weigh about 40mg of 1MT, dissolve in 2mL NaOH aqueous solution, drop into 10mL 2-methylimidazole aqueous solution (62.5mg / mL) under stirring condition, and then add R837 and Zn(NO 3 ) 2 ·6H 2 The O suspension was dropped into the mixed solution of 1MT and 2-methylimidazole under stirring conditions, and the drug-loaded MOF nanoparticles formed spontaneously. The suspension was centrifuged, washed with DMSO, washed with water, the supernatant was discarded, and vacuum-dried to obtain a white solid. (R837+1MT)@ZIF-8.

[0073](R837+1MT)@ZIF-8 was uniformly dispersed in 2 mL of 50 mg / mL mannan (MAN) aqu...

Embodiment 3

[0076] Example 3: In vivo pharmacodynamics test of HA / IR820@ZIF-8 and MAN / (R837+1MT)@ZIF-8 in the treatment of solid tumors by intravenous injection.

[0077] 1. Construction of melanoma mouse model:

[0078] Take 20 healthy female C57BL6 mice aged 6-8 weeks, place them in a suitable environment, and raise them for 1 week. After the mice adapted to the environment, inoculate 0.1mL density of 1×10 7 / mL mouse melanoma (B16F10) cell suspension, continue to feed after inoculating the cells. Mice were checked daily for tumor growth in the axilla of the right forelimb. When the tumor volume (V=1 / 2×length×width 2 ) to about 100mm 3 After that, the tumor suppression experiment was started.

[0079] 2. In vivo tumor inhibition experiment:

[0080] Using female C57BL6 mice bearing B16F10 mouse melanoma cells as an animal model, the in vivo anti-tumor effects of HA / IR820@ZIF-8 and MAN / (R837+1MT)@ZIF-8 were explored. The mice were randomly divided into 4 groups, 5 in each group. ...

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Abstract

The invention provides a hybrid nanometer drug administration system based on a metal organic framework, and a preparation method and an application of the nanometer drug administration system. The hybrid nanometer drug administration system based on the metal organic framework comprises a targeted functional material, a metal organic framework material and an active drug material, wherein the active drug material is loaded to holes of the metal organic framework, and the surface of the metal organic framework material loads the targeted functional material; the active drug material is one ormore of a photothermal conversion agent, an adjuvant and an immunomodulator; and the targeted functional material is a hyaluronic acid and / or mannan. Through the hybrid nanometer drug administrationsystem based on the metal organic framework, an accurate, safe and effective anti-tumor treatment is realized.

Description

technical field [0001] The disclosure belongs to the technical field of medicine, and relates to a metal-organic framework-based nano drug delivery system and its preparation method and application. Background technique [0002] The statements herein merely provide background information related to the present disclosure and may not necessarily constitute prior art. [0003] With the increasing morbidity and mortality of malignant tumors, malignant tumors have become the primary factor threatening public health, and the treatment of malignant tumors is urgent. Current tumor treatment methods mainly include surgical resection, chemotherapy, radiotherapy, photothermal therapy, photodynamic therapy, and immunotherapy. However, traditional surgical resection, chemotherapy, and radiotherapy are difficult to achieve effective treatment after malignant metastasis of the tumor occurs. Certain limitations. [0004] Immunotherapy mainly achieves tumor treatment by activating the bod...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K31/405A61K39/39A61K47/61A61K47/69A61P35/00A61P37/04
CPCA61K31/405A61K39/39A61K41/0052A61K47/61A61K47/6949A61K2039/55511A61P35/00A61P37/04A61K2300/00
Inventor 栾玉霞张会苑
Owner SHANDONG UNIV
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