NO-loaded supramolecular polypeptide nano-drug as well as preparation method and application thereof

A nano-drug and supramolecular technology, applied in the field of biomedicine, can solve the problems of single nano-drug structure and inability to solve multidrug resistance of tumors, and achieve the effects of reversing multidrug resistance, improving uptake and simple operation.

Pending Publication Date: 2022-07-08
NANTONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The purpose of the present invention is to provide a supramolecular polypeptide nano-medicine loaded with NO and its preparation method and its application in the preparation of anti-tumor drugs, so as to solve the singl

Method used

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  • NO-loaded supramolecular polypeptide nano-drug as well as preparation method and application thereof
  • NO-loaded supramolecular polypeptide nano-drug as well as preparation method and application thereof
  • NO-loaded supramolecular polypeptide nano-drug as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 1. Preparation of pyridine-poly(L-cysteine)-S-nitroso

[0040]

[0041] Step 1: Obtain 1-(4-aminobutyl)pyridine hexafluorophosphate and S-o-nitrobenzyl-L-cysteine ​​with reference to existing literature. In the glove box, take 7.5 mg of 1-(4-aminobutyl)pyridine hexafluorophosphate, dissolve it in 1 mL of anhydrous N,N-dimethylformamide, and then add S-o-nitrobenzyl-L -200 mg of cysteine, after 48 hours of reaction at room temperature, the reaction solution was settled in 8 mL of anhydrous ether, centrifuged again, repeated 3 times, and vacuum dried for 24 hours to obtain 178.5 mg of white solid. Yield 83.5-87.2%.

[0042]Step 2: Dissolve 50 mg of the white solid obtained in step 1 in a mixed solvent of 100 mL of anhydrous N,N-dimethylformamide / anhydrous acetonitrile (volume ratio is 4:1) to prepare a concentration of 0.5 mg / mL The solution was placed under a UV LED lamp (wavelength 365nm, power 150W) for 12h, so that the ortho-nitrobenzyl (NB) in the polymer was ph...

Embodiment 2

[0048] Effects of NO-loaded supramolecular polypeptide nanomedicines on multidrug-resistant human breast cancer cells

[0049] The NO-loaded supramolecular polypeptide nanomedicine (WPC / DOX-ICG) prepared in Example 1, the NO-loaded supramolecular polypeptide nanomedicine (WPC / DOX) without indocyanine green, and the The NO-loaded supramolecular polypeptide nanomedicine (WPC / ICG) and doxorubicin (DOX) were prepared in cell culture medium to prepare doxorubicin concentrations of 0.2, 0.5, 1, 2, 5, and 10 μg / mL, respectively. , the corresponding concentrations of indocyanine green were 0.14, 0.34, 0.68, 1.36, 3.38, and 6.72 μg / mL, respectively, and then cultured with MCF-7 / ADR cells (multidrug-resistant human breast cancer cells) for 48 hours. In addition, for the supramolecular polypeptide nanomedicines loaded with NO and the supramolecular polypeptide nanomedicines loaded with NO without doxorubicin (WPC / ICG), another group needs to be set up. It is illuminated for 5min (808nm,...

Embodiment 3

[0052] Effect of NO-loaded supramolecular polypeptide nanomedicine on HeLa tumor growth

[0053] The mice inoculated with HeLa tumor were divided into 5 groups: saline, doxorubicin (5 mg / kg), NO-loaded supramolecular polypeptide nanomedicine (2 mg / mL) without indocyanine green, uncoated indocyanine green. NO-loaded supramolecular polypeptide nanomedicine (2mg / mL) + NIR, NO-loaded supramolecular polypeptide nanomedicine (2mg / mL), NO-loaded supramolecular polypeptide nanomedicine (2mg / mL) encapsulated with doxorubicin )+NIR. The injection was once on the 0th day, and 12 hours after the injection, the NO-loaded supramolecular polypeptide nanomedicine+NIR and the NO-loaded supramolecular polypeptide nanomedicine+NIR were illuminated for 5 min (808 nm, 1W / cm) after the injection. 2 ), while the tumor volume was measured every other day, the results are as follows Figure 4 shown.

[0054] Figure 4 Among them, the abscissa represents the days of mice receiving the experiment, a...

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Abstract

The invention discloses an NO-loaded supramolecular polypeptide nano-drug as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The NO-loaded supramolecular polypeptide nano-drug is prepared from pyridine-poly (L-cysteine)-S-nitroso group, column [5] arene, adriamycin and indocyanine green. The NO-loaded supramolecular polypeptide nano-drug is prepared through the host-guest interaction of water-soluble column [5] arene and pyridinium salt, and is used for simultaneously conveying a chemotherapeutic drug adriamycin and a photothermal conversion agent indocyanine green. Under irradiation of near-infrared light, indocyanine green absorbs light energy and converts the light energy into heat energy, and meanwhile, the heat energy enables the nano-drug to release NO, so that multidrug resistance of tumors is reversed, the chemotherapy effect of adriamycin is synergistically promoted, and triple synergistic treatment of photo-thermal treatment-NO gas treatment-chemotherapy is formed.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a NO-loaded supramolecular polypeptide nanomedicine, a preparation method thereof, and an application in the preparation of antitumor medicines. Background technique [0002] Cancer seriously threatens human survival and social development, and is a recognized public health problem all over the world. How to effectively treat cancer has become a global problem. At present, clinical chemotherapy is still one of the main methods for the treatment of cancer. However, chemotherapy often has the risk of killing normal cells, destroying the immune system and increasing the incidence of secondary cancers, and the emergence of multidrug resistance also seriously affects the efficacy of chemotherapy. As a human endogenous gas, nitric oxide (NO) can not only inhibit tumor growth at high concentrations, but also induce tumor cell apoptosis, and even directly kill tumor cel...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K33/00A61K31/704A61K47/69A61P35/00
CPCA61K41/0052A61K33/00A61K31/704A61K47/6949A61P35/00A61K2300/00Y02A50/30
Inventor 丁月马宇轩王陈威朱吕明
Owner NANTONG UNIVERSITY
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