A kind of hypoxia responsive polymer nanoparticle and its application

A nanoparticle and polymer technology, which is applied in the field of nanomaterial preparation and biomedicine, can solve the problems of reducing active oxygen species in local tumor tissues, limiting the clinical application of cancer treatment, and affecting the effect of photodynamic therapy, so as to enhance the joint killing ability, Achieving synergistic therapeutic effects and avoiding destructive effects

Active Publication Date: 2020-05-05
MENGCHAO HEPATOBILIARY HOSPITAL OF FUJIAN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most small-molecule photosensitizers exhibit strong hydrophobic properties, low water solubility, and low tumor-targeting properties
In addition, the process of photodynamic therapy rapidly depletes tissue oxygen and disrupts tumor blood flow, leading to tissue hypoxia and reducing the production of reactive oxygen species in local tumor tissue.
This affects the effect of photodynamic therapy and limits the clinical application in cancer therapy

Method used

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  • A kind of hypoxia responsive polymer nanoparticle and its application
  • A kind of hypoxia responsive polymer nanoparticle and its application
  • A kind of hypoxia responsive polymer nanoparticle and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Synthesis of polymer nanomedicine: Weigh 4.2mg 4,4'-Azodianiline (4,4'-Azodianiline, 0.02mmol) and 2.7mg terephthalaldehyde (0.02mmol) and dissolve in 4mL N,N- In the dimethylformamide (DMF) solution, 0.2 mL of glacial acetic acid (98%) was added to initiate the polymerization reaction for 5 minutes. 400 μL of 2 mg / mL CPT (camptothecin, CPT, as the chemotherapeutic drug in this example) was added to the polymer solution, mixed well, and the reaction was continued for 5 minutes. Under stirring conditions, the above mixed solution was added dropwise to 20mL of 1mg / mL polyvinylpyrrolidone (PVP, molecular weight 40K) aqueous solution. After the addition was completed, the ultrasonic reaction was performed for 5 minutes, and the stirring was continued for 10 minutes, and then 400μL of 2mg / mL was added dropwise. The DMF solution of chlorin e6 (Ce6, as the photosensitizer in this example) was continued to react for 30 minutes. Centrifuge the reacted solution at 6000 rpm for 5 ...

Embodiment 2

[0042] The polymer nanomedicine synthesized in Example 1 was characterized by related physical and chemical properties to prove that the polymer nanomedicine was successfully synthesized. It is characterized by transmission electron microscope (TEM), particle size tester (DLS), ultraviolet-visible spectrophotometer (UV-Vis), fluorescence spectrometer, etc. In addition, to verify the ability of polymer nanomedicine to generate active oxygen under 670nm laser irradiation, use 9,10-anthryl-bis(methylene)dimalonic acid (ABDA) as the active oxygen indicator, and polymer nano After the drug is mixed with ABDA, the laser is irradiated for different time, the absorption value change at 380nm is tested, normalized, and compared with the sample without light irradiation, it proves the active oxygen generation ability of the polymer nano drug. To investigate the ability of nano-polymer drugs to respond to reductase, select sodium dithionite (Na 2 S 2 O 4 ) Is a reductase mimic, which is t...

Embodiment 3

[0048] Taking cervical cancer cells (HeLa cells) as a model, using confocal fluorescence microscopy to test the ability of polymer nanomedicine to carry drugs and photosensitizers at the cell level; combined with the fluorescent indicator of reactive oxygen species 2',7'-dichlorofluorescein diacetate (DCFH-DA) to investigate the ability of polymer nanomedicine to generate reactive oxygen species in cells; combined with a live and dead double dye fluorescent indicator (calcein-propidium iodide Calcein-AM-PI) to investigate polymer nanomedicine in light and no light The effect of treatment under light conditions. The cell viability quantitative detection kit (CCK-8 kit) is used to quantitatively test the therapeutic effect of polymer nanomedicine under light and non-light conditions.

[0049] The specific test results are as follows:

[0050] (1) After the polymer nanomedicine was incubated with HeLa cells for 4 hours, the fluorescence of Ce6 and CPT were detected by a confocal fluo...

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Abstract

The invention relates to a hypoxia response polymer nanoparticle and application thereof. The method comprises the following steps: firstly crosslinking 4,4-diaminoazobenzene and terephthalaldehyde taken as monomers, so as to form a conjugated polymer link, loading a photosensitizer and chemotherapy drugs through noncovalent interaction, and then forming the hypoxia response polymer nanoparticle through a nanoprecipitation method. The hypoxia response polymer nanoparticle can successfully carry the photosensitizer and the chemotherapy drugs to tumor cells, and produce active oxygen during illumination, so as to realize tumor killing. Azo bonds contained in the nanoparticle can be degraded under the action of reductase in cells, and chemotherapy drug release is realized. In addition, cell hypoxia caused during a photodynamic therapy process can further improve drug release, and the hypoxia response polymer nanoparticle can properly realize excellent tumor therapy effect through combination therapy effect of photodynamic therapy and chemical therapy.

Description

[0001] (1) Technical field [0002] The invention belongs to the fields of nano material preparation and biomedicine, and specifically relates to a hypoxia-responsive polymer nanoparticle and its application in the preparation of anti-tumor drugs. [0003] (2) Background technology [0004] Cancer is currently one of the main causes of global morbidity and death. It is a major disease that seriously endangers human life and health and restricts social and economic development. Chemotherapy, which uses chemical anticancer drugs to destroy and inhibit the growth of tumor cells, is an indispensable choice for most cancer treatments due to its high efficiency and drug specificity. However, chemotherapy often has certain limitations due to the small molecular size and low water solubility of chemical drugs, such as lower bioavailability, faster blood or kidney clearance, non-specific selectivity, and low tumor enrichment rate , Severe drug resistance, side effects on normal tissues, etc....

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4745A61K41/00A61K45/06A61K47/69A61K47/59A61P35/00
CPCA61K31/4745A61K41/0071A61K45/06A61K47/6935A61P35/00A61K2300/00
Inventor 张晓龙刘景丰刘小龙曾永毅吴名
Owner MENGCHAO HEPATOBILIARY HOSPITAL OF FUJIAN MEDICAL UNIV
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