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Hypoxia response polymer nanoparticle and application thereof

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 therapeutic effects and avoiding destructive effects

Active Publication Date: 2018-10-16
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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  • Hypoxia response polymer nanoparticle and application thereof
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  • Hypoxia response polymer nanoparticle and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Synthesis of polymer nanomedicine: Weigh 4.2mg 4,4-Azodianiline (4,4'-Azodianiline, 0.02mmol) and 2.7mg terephthalaldehyde (terephthalaldehyde, 0.02mmol) and dissolve in 4mL N,N- Add 0.2 mL of glacial acetic acid (98%) to the dimethylformamide (DMF) solution to initiate polymerization for 5 minutes. Add 400 μL of 2 mg / mL CPT (camptothecin, CPT, as the chemotherapeutic drug in this example) into the polymer solution, mix well, and continue to react for 5 minutes. Under the condition of stirring, add the above mixed solution dropwise to 20mL of 1mg / mL polyvinylpyrrolidone (PVP, molecular weight 40K) aqueous solution, after the dropwise addition, after ultrasonic reaction for 5 minutes, continue to stir for 10 minutes, then add dropwise 400μL of 2mg / mL The DMF solution of chlorin e6 (Ce6, as the photosensitizer in this embodiment) was continued to react for 30 minutes. Centrifuge the reacted solution at 6000rpm for 5 minutes, remove the precipitate, centrifuge the upper l...

Embodiment 2

[0037]The relevant physicochemical properties of the polymer nanomedicine synthesized in Example 1 were characterized to prove the successful synthesis of the polymer nanomedicine. It is characterized by transmission electron microscope (TEM), particle size tester (DLS), ultraviolet-visible spectrophotometer (UV-Vis), and fluorescence spectrometer. In addition, to verify the ability of polymer nanomedicine to generate active oxygen under 670nm laser irradiation, 9,10-anthracenyl-bis(methylene) dimalonic acid (ABDA) was used as active oxygen indicator, polymer nano After the drug was mixed with ABDA, the laser was irradiated for different times, and the absorption value change at 380nm was tested, normalized, and compared with the non-light-irradiated sample to prove the active oxygen generation ability of the polymer nano-medicine. To investigate the ability of nanopolymer drugs to respond to reductases, sodium dithionite (Na 2 S 2 o 4 ) is a reductase simulant, by testing ...

Embodiment 3

[0043] Using cervical cancer cells (HeLa cells) as a model, using confocal fluorescence microscopy to test the ability of polymer nanomedicines to carry drugs and photosensitizers at the cell level; combined with reactive oxygen species fluorescent indicator 2',7'-dichlorofluorescein diacetate (DCFH-DA) to investigate the ability of polymer nanomedicine to generate reactive oxygen species in cells; combined with live-dead double-stained fluorescent indicator (calcein-propidium iodide Calcein-AM-PI) to investigate the ability of polymer nanomedicine under light and without Therapeutic effect under light conditions. Using the Cell Viability Quantitative Detection Kit (CCK-8 kit), quantitatively test the therapeutic effect of the polymer nanomedicine under light and no light conditions.

[0044] The specific test results are as follows:

[0045] (1) After co-incubating the polymer nanomedicine with HeLa cells for 4 hours, the fluorescence of Ce6 and CPT were detected by confocal...

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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

(1) Technical field [0001] The invention belongs to the fields of nanomaterial preparation and biomedicine, and in particular relates to a hypoxia-responsive polymer nanoparticle and its application in the preparation of antitumor drugs. (2) Background technology [0002] Cancer is one of the main causes of morbidity and death in the world, and 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 tumor cell growth, is an indispensable choice for most cancer treatments because of 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 low bioavailability, fast blood or kidney clearance rate, non-specific selectivity, and low tumor accumulation rate , severe drug resistance, side effects on normal tissues, etc. [0003] ...

Claims

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Application Information

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Patent Type & Authority Applications(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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