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Hypoxia response chiral medicament micelle for targeting triple-negative breast cancer and preparation method of hypoxia response chiral medicament micelle

A technology for triple-negative breast cancer and chiral drugs, which is applied in the directions of drug combinations, pharmaceutical formulations, and non-active ingredients medical preparations to achieve the effects of improving drug utilization, bioavailability, and anti-tumor effects

Active Publication Date: 2020-10-09
NANTONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few studies on drug carriers based on azo-hypoxic response, and we need to design effective azo-hypoxic-responsive nanocarriers to meet the challenge of hypoxic environment encountered in traditional tumor therapy.

Method used

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  • Hypoxia response chiral medicament micelle for targeting triple-negative breast cancer and preparation method of hypoxia response chiral medicament micelle
  • Hypoxia response chiral medicament micelle for targeting triple-negative breast cancer and preparation method of hypoxia response chiral medicament micelle
  • Hypoxia response chiral medicament micelle for targeting triple-negative breast cancer and preparation method of hypoxia response chiral medicament micelle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[0037] Preparation of AS1411 modified polyethylene glycol-azobenzene-dextrorotary polylactic acid block copolymer:

[0038] (1) Dissolve 50 mg (1 equivalent) of carboxypolyethylene glycol active ester (COOH-PEG-NHS, MW=1000) in 6 mL of dichloromethane, and add 6.8 mg (1.3 equivalents) of 4,4-azobis Aniline (AZO), after reacting for 24 hours at room temperature under stirring in the dark, concentrate the reaction solution obtained from the reaction, add 25mL of glacial ether for purification, let it stand overnight and then centrifuge, and dry the precipitate obtained by centrifugation to obtain carboxypolyethylene glycol azobenzene (COOH-PEG-AZO-NH 2 );

[0039] (2) Dissolve 50 mg (1.3 equivalents) of carboxy-dextrorotary polylactic acid (COOH-PDLA, MW=2000) in 5 mL of dichloromethane, and add 8 mg (2 equivalents) of dicyclohexylcarbodiimide (DCC) and 5 mg ( 2.3 equivalents) of N-hydroxysuccinimide (NHS), after stirring for 30 minutes at room temperature, add 41 mg (1 equiva...

Embodiment 1-2

[0042] Preparation of AS1411 modified polyethylene glycol-azobenzene-dextrorotary polylactic acid block copolymer:

[0043] Carboxylated polyethylene glycol active ester (COOH-PEG-NHS, MW=1000) in step (1) of Example 1-1 was replaced by carboxylated polyethylene glycol active ester (COOH-PEG-NHS, MW=2000) , and then prepare AS1411-modified polyethylene glycol-azobenzene-dextrorotatory polylactic acid block copolymer (AS1411-PEG-AZO-PDLA) according to step (2) and step (3) of Example 1-1.

Embodiment 1-3

[0045] Preparation of AS1411 modified polyethylene glycol-azobenzene-dextrorotary polylactic acid block copolymer:

[0046] Carboxylated polyethylene glycol active ester (COOH-PEG-NHS, MW=1000) in step (1) of Example 1-1 was replaced by carboxylated polyethylene glycol active ester (COOH-PEG-NHS, MW=5000) , and then prepare AS1411-modified polyethylene glycol-azobenzene-dextrorotatory polylactic acid block copolymer (AS1411-PEG-AZO-PDLA) according to step (2) and step (3) of Example 1-1.

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Abstract

The invention belongs to the technical field of nano-medicaments, and discloses a hypoxia response chiral medicament micelle for targeting triple-negative breast cancer and a preparation method of thehypoxia response chiral medicament micelle. The preparation method comprises the following steps: firstly, introducing an azobenzene group into a molecular chain of carboxyl polyethylene glycol active ester, and obtaining carboxyl polyethylene glycol azobenzene; then, preparing the carboxyl polyethylene glycol-azobenzene-dextrorotatory polylactic acid segmented copolymer through reaction with carboxyl dextrorotatory polylactic acid; then introducing an amino-modified aptamer AS1411 to prepare AS1411-modified polyethylene glycol-azobenzene-dextral polylactic acid, compounding a fat-soluble anti-cancer drug, and then dialyzing to obtain the micelle disclosed by the invention. The low-oxygen-response chiral medicament micelle provided by the invention is small in particle size and narrow indistribution, and can be effectively retained at a targeted part; low-oxygen responsiveness is achieved, and the effect of low-oxygen slow release is achieved; TNBC tumors can be targeted, anti-cancerdrugs are selectively released, and the anti-tumor effect is remarkably improved.

Description

technical field [0001] The invention belongs to the technical field of nano-pharmaceuticals, and in particular relates to a hypoxia-responsive chiral drug micelle targeting triple-negative breast cancer and a preparation method thereof. Background technique [0002] Breast cancer is the most common malignant tumor in women all over the world, and 90% of the deaths of breast cancer patients are caused by tumor metastasis. As a subtype of breast cancer, triple-negative breast cancer (TNBC) has the worst survival rate because of its highly metastatic and invasive tumor cells. At the same time, the cancer cell population of TNBC often develops drug resistance due to its high invasiveness and self-renewal ability. This makes the free drug therapy ineffective, unable to eradicate cancer cells, and unable to stop tumor metastasis process. [0003] Nano-drug carrier is a sub-particle drug carrier delivery system belonging to the category of nano-scale microcosm. Nanomedicines sma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/34A61K47/10A61K31/704A61K31/337A61K31/4745A61P35/00
CPCA61K9/1075A61K47/34A61K47/10A61K31/704A61K31/337A61K31/4745A61P35/00
Inventor 陈忠平陆敏刘雪蒙龙朦朦翁凌燕朱俐
Owner NANTONG UNIVERSITY
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