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Adenosine monophosphate AMP complex and application thereof in preparation of tumor targeting nano-drug delivery system

A technology of adenosine monophosphate and drug delivery system, applied in the field of preparation of tumor-targeted nano drug delivery system, which can solve the problem of less drugs for brain tumors

Inactive Publication Date: 2019-07-26
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, because the BBB is intact in the early stage of brain tumor growth, even in the middle and late stages, there is always a BBB in the infiltration of brain tumor cells, resulting in few clinical drugs for the treatment of brain tumors. The current first-line drug is only Temozolomide

Method used

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  • Adenosine monophosphate AMP complex and application thereof in preparation of tumor targeting nano-drug delivery system
  • Adenosine monophosphate AMP complex and application thereof in preparation of tumor targeting nano-drug delivery system
  • Adenosine monophosphate AMP complex and application thereof in preparation of tumor targeting nano-drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] AMP-FAM, AMP-drug complex, AMP-PEG 3400 -Synthesis and characterization of DSPE

[0072] Synthesis of AMP-FAM:

[0073] AMP was first reacted with hexamethylenediamine to generate AMP amino derivatives: 744g of AMP and 928g of 1,6-hexamethylenediamine were dissolved in water, and the pH was adjusted to 6.5 with HCl. After that, EDC was added slowly and reacted at room temperature for 90 min. Dowex 50WX8-200 cation exchange resin was used to purify the reaction product, and freeze-dried to obtain AMP amino derivatives;

[0074] AMP amino derivatives and FAM are dissolved in DMF, EDC and DIPEA equivalent to AMP amino derivatives are added, the reaction is stirred at room temperature, monitored by HPLC, the reaction is stopped after the reaction is complete, and the preparative liquid phase is used for purification, and acetonitrile / water (containing 0.1% TFA) system elution, freeze-dried to obtain AMP-FAM pure product;

[0075] Preparation of AMP-DTPA-Gd and AMP-DTPA-...

Embodiment 2

[0082] Preparation and Characterization of Example 2 Nanodiscs

[0083] Prepare blank Nanodiscs:

[0084] Prepared by thin-film hydration method, the nano-disc (Disks) film formulation is POPC: Chol: mPEG 2000 -DSPE=35:40:25 (mol / mol); AMP-modified nano-disc (AMP-Disks) film formulation is POPC:Chol:mPEG 2000 -DSPE: AMP-PEG 3400 -DSPE=35:40:23:2 (mol / mol), the film material was dissolved in chloroform, and the organic solvent was removed by rotary evaporation at 40°C, so that the film material formed a thin film on the bottle wall, placed in a vacuum oven, evaporated Net organic solvents. After 24 hours, add PBS, oscillate on a water bath shaker at 37°C for 1 hour, sonicate the probe for 45 minutes, and filter with a 0.22 μm filter membrane to obtain Disks and AMP-Disks.

[0085] Preparation of DiO, DiI and DiD loaded nanodiscs:

[0086] Use acetonitrile to dissolve DiO, DiI and DiD, and form a film together with the above-mentioned disc membrane materials. The subsequent...

Embodiment 3

[0091] Example 3 Detection of Adenosine Receptors

[0092] U87 and bEnd.3 cells were lysed with lysate (1% Triton X-100, NaCl 150mmol / L, Tris-HCl (pH 7.4, 50mmol / L), 0.5% SDS). Place the sample to be lysed on ice, and add the lysate at a ratio of 200 μl / well (6-well plate). Lyse for about 10 minutes, and transfer the lysed mixture to a 1.5ml EP tube. Add methanol and chloroform according to the ratio of lysate:methanol:chloroform=1:1:0.25, and mix well. Centrifuge for 5 minutes, discard the supernatant, then add methanol equal to the volume of the lysate, mix well, centrifuge for 5 minutes, discard the supernatant, and obtain a protein precipitate. Dry for about 10 minutes, add the loading buffer to resuspend the protein, boil for 10 minutes to prepare the sample, and detect adenosine A by Western-Blot 1 receptor, the result is as Figure 6 shown.

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Abstract

The invention belongs to the field of pharmacy, and relates to an AMP complex and an application thereof in preparation of a tumor targeting nano-drug delivery system. The invention provides a drug and a polymer carrier material modified by adenosine monophosphate (AMP) and an application thereof in construction of a drug delivery system for tumor imaging and targeting therapy. Experimental results show that the AMP complex can cross brain capillary endothelial cells, are specifically absorbed by tumor tissues and have good intracerebral delivery and tumor targeting and imaging functions. Thenano-drug delivery system constructed by the AMP-modified polymer carrier material, such as liposomes, polymer micelles, polymer discs and nanoparticles, can cross a blood-brain barrier to enter the brain and target to tumors, and significantly enhances antitumor effects. The AMP-modified drug and the nano-drug delivery system have remarkable advantages in targeting brain tumors, and have good application prospects in targeting diagnosis and treatment of tumors.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to an AMP compound and its application in preparing a tumor-targeting nano drug delivery system. Adenosine A 1 Adenosine monophosphate (AMP)-modified drug complexes and modified nano-drug delivery systems that cross the blood-brain barrier and target tumors. The constructed nano-drug delivery systems include liposomes, polymer micelles, polymeric Object discs, nanoparticles, etc. can be used for the diagnosis and targeted therapy of brain tumors or peripheral tumors. Background technique [0002] The prior art discloses that the blood-brain barrier (BBB) ​​is a characteristic structure unique to brain capillaries, which can act as a barrier to substances passing through surrounding blood vessels, thereby maintaining a stable environment in the brain tissue and protecting the brain tissue. role. BBB can also restrict the transport of drugs from the blood to the brain, making it difficult for...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/54A61K47/34A61K47/26A61K9/107A61K9/50A61P35/00
CPCA61K47/549A61K47/34A61K47/26A61K9/1075A61K9/5031A61P35/00
Inventor 陆伟跃代同成谢操
Owner FUDAN UNIV
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