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Preparation method of angelica polysaccharide derivative for sensitizing ferroptosis through hypoxia response

A polysaccharide derivative and ferroptosis technology, which is applied in the field of biomedicine, can solve the problems of poor prognosis and insignificant effect of tumor therapy, and achieve the effects of drug release, promotion of ferroptosis, and increase of ROS concentration.

Active Publication Date: 2022-01-21
济南天聚牧业科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the liver-targeting property of angelica polysaccharides, the existing ones have a certain effect on the treatment of liver cancer, but the effect is not significant
[0003] Immunosuppressive cells, tumor stem cells, and circulating tumor cells in the tumor hypoxic microenvironment can mediate immunosuppression and immune tolerance, promote tumor development, and lead to poor prognosis and therapeutic resistance of tumor therapy

Method used

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  • Preparation method of angelica polysaccharide derivative for sensitizing ferroptosis through hypoxia response
  • Preparation method of angelica polysaccharide derivative for sensitizing ferroptosis through hypoxia response
  • Preparation method of angelica polysaccharide derivative for sensitizing ferroptosis through hypoxia response

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Embodiment

[0036] This embodiment relates to a preparation method of angelica polysaccharide derivatives that respond to hypoxia and sensitize ferroptosis, comprising the following steps:

[0037] Step 1, synthesis of carrier material: firstly carry out the synthesis of angelica polysaccharide-azophthalic acid, then the synthesis of angelica polysaccharide-azophthalic acid-ferrocenemethanol, and finally form arachidonic acid-angelica polysaccharide-azo Phthalic acid-ferrocenemethanol;

[0038] In step 2, the carrier material is subjected to dialysis and freeze-drying treatment.

[0039] Preferably, in step 1, the synthetic method of described angelica polysaccharide-azophthalic acid is: see figure 1 Shown: Angelica polysaccharide with liver-targeting properties is used as the hydrophilic block, and the azophthalic acid hypoxia-sensitive bond is connected by esterification reaction, and the mass ratio of azophthalic acid is 1:1, and the hydrophilic block is prepared. Component ASP-AZO; ...

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Abstract

The invention provides a preparation method of an angelica polysaccharide derivative for sensitizing ferroptosis through hypoxia response. The preparation method comprises the following steps: S1, carrying out synthesis of a carrier material: firstly, synthesizing angelica polysaccharide-azobenzoic acid, then synthesizing angelica polysaccharide-azobenzoic acid-ferrocene methanol, and finally, forming arachidonic acid-angelica polysaccharide-azobenzoic acid-ferrocene methanol; and S2, carrying out dialysis and freeze-drying treatment on the carrier material. According to the preparation method disclosed by the invention, by introduction of exogenous iron ferrocene, introduction of a ferroptosis precursor arachidonic acid and consumption of NADPH, which is caused by azobenzene bond degradation, ferroptosis is selectively sensitized, and cancer cell death is synergistically promoted. Reduction of azobenzene bonds involved in the preparation method disclosed by the invention causes a failure of the tumor NADPH, so that the concentration of intracellular GSH and Trx is reduced, the concentration of intracellular ROS is increased, and tumor cell ferroptosis is indirectly promoted. Based on liver targeting and passive targeting of angelica polysaccharide, the preparation method fulfills the aim of accurate tumor targeting drug delivery of the derivative.

Description

technical field [0001] The invention belongs to the technical field of biomedicine; in particular, it relates to a method for preparing an angelica polysaccharide derivative that responds to hypoxia and increases sensitivity to ferroptosis. Background technique [0002] In recent years, polysaccharides are one of the most active directions in the field of research in the new century, especially the research on the structure and pharmacological activity of natural macromolecular plant polysaccharides. Angelica is a Umbelliferae plant, enters the liver and spleen, has the functions of nourishing blood, promoting blood circulation, protecting the liver and protecting the spleen, etc. It is one of the most frequently used traditional Chinese medicines in clinical practice, and is known as "ten directions and nine returns". active ingredient. Due to the liver-targeting property of angelica polysaccharides, the existing methods have a certain effect on treating liver cancer, but ...

Claims

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Application Information

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IPC IPC(8): A61K47/61A61K47/54A61K31/202A61P35/00C08B37/00
CPCA61K47/61A61K47/542A61K47/541A61K31/202A61P35/00
Inventor 陈大全刘雪郭春静李毅于采薇陈强苏彦国郭慧敏孔明
Owner 济南天聚牧业科技有限公司
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