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Tumor sub-acidity sensitive copper-drug commonly-coordinated self-assembled nanoparticles and application

A nanoparticle, slightly acidic technology, applied in the direction of antineoplastic drugs, drug combinations, pharmaceutical formulations, etc., to achieve good clinical application prospects, reduce phagocytosis, and improve the effect of drug systemic circulation time

Active Publication Date: 2017-08-04
FUZHOU HOSPITAL FOR INFECTIOUS DISEASE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, under hypoxic or hypoxic conditions, DOX is easily effluxed by tumor cells and induces tumor tolerance

Method used

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  • Tumor sub-acidity sensitive copper-drug commonly-coordinated self-assembled nanoparticles and application
  • Tumor sub-acidity sensitive copper-drug commonly-coordinated self-assembled nanoparticles and application
  • Tumor sub-acidity sensitive copper-drug commonly-coordinated self-assembled nanoparticles and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033]Use an electronic balance to weigh 1 mg of doxorubicin hydrochloride Doxorubicin-HCl ((2R,4S)-4-(3-Amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyloxy)-2-hydroxyacetyl -1,2,3,4-tetrahydro-2,5,12-trihydroxy-7-methoxynaphthacene-6,11-dione, Sigma company) red powder and 1mg of Banoxantrone (1,4-Bis[2-(dimethylamino -N-oxide)ethylamino]-5,8-dihydroxyanthracene-9,10-dione, Abcam) blue powder was dissolved in 2ml of deionized water, after stirring for 1h, 0.1mL of 1mg / mL CuCl was added 2 - pH 7.4 (adjust the pH with NaOH), and stir for 4 h, then add 0.45 mL of triethylamine solution to desalt the mixture. After stirring for 24 hrs under dark conditions, the mixture was added dropwise to 10 mL of deionized water, and stirred at 1000 rpm / min. Then it was placed in a 14400Da dialysis bag for dialysis, and 1L of deionized water was replaced every 4 hours. After 2 days of dialysis, the solution was centrifuged at a low speed of 1000rpm / min to remove aggregates, and then the nanoparti...

Embodiment 2

[0035] The Nanodrug nanoparticles prepared in Example 1 have a diameter of about 80-100 nm, and have pH-sensitive near-infrared fluorescence imaging, controlled drug release, and synergistic anti-tumor effects of aerobic and hypoxic properties.

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Abstract

The invention relates to Nanodrug nanoparticles for realizing pH (Potential of Hydrogen) imaging of a tumor microenvironment, drug controlled release and cooperated chemotherapy effect on tumors. The Nanodrug nanoparticles are prepared through commonly coordinating a clinical commonly used chemotherapy drug Doxorubicin and a biological reduction drug (Banoxantrone) with bivalent copper ions through a self-assembling synthesis method. The Nanodrug nanoparticles provided by the invention can be used for intelligently adjusting a nano-scale according to different pH gradients of the tumor microenvironment and can effectively permeate tumor epithelial cells and express drug controlled release and cooperated anti-tumor activity under an aerobic / anoxic condition; the tumor anoxic tolerance of the drugs is solved and the potential toxic and side effects caused by the anthracycine chemotherapy drugs on patients is reduced.

Description

[0001] (1) Technical field [0002] The invention relates to a copper ion-medicine co-coordinating self-assembled nanoparticle used for slightly acidic tumors and its application. [0003] (2) Background technology [0004] Tumor is a common and frequently-occurring disease, among which malignant tumor is the most serious disease that endangers human health. In some European and American countries, the mortality rate of malignant tumors ranks second only to cardiovascular diseases. The most common and serious tumors in my country are lung cancer, nasopharyngeal cancer, esophageal cancer, gastric cancer, colorectal cancer, liver cancer, breast cancer, cervical cancer, leukemia and lymphoma. At present, the treatment of malignant tumors is mostly based on surgical resection, but many patients lose the opportunity for surgical treatment due to the influence of tumor location and physical tolerance status when they are diagnosed. Adjuvant treatments such as local radiotherapy and...

Claims

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Application Information

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IPC IPC(8): A61K9/52A61K47/52A61K31/704A61K31/14A61P35/00
CPCA61K9/0002A61K9/5115A61K31/14A61K31/704A61K2300/00
Inventor 张达刘小龙吴名刘景丰
Owner FUZHOU HOSPITAL FOR INFECTIOUS DISEASE
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