Cucurbitacin B and oxidation-responsive antitumor prodrug co-loaded bionic nanoparticle

A technology of biomimetic nano and anti-tumor drugs, applied in the field of medicine, can solve the problem that immune clearance cannot target circulating tumor cells

Inactive Publication Date: 2020-04-14
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Specifically, the first purpose of the present invention is to overcome the shortcomings of traditional nano-medicines that are easy to be immune cleared and unable to target circulating tumor cells, and

Method used

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  • Cucurbitacin B and oxidation-responsive antitumor prodrug co-loaded bionic nanoparticle
  • Cucurbitacin B and oxidation-responsive antitumor prodrug co-loaded bionic nanoparticle
  • Cucurbitacin B and oxidation-responsive antitumor prodrug co-loaded bionic nanoparticle

Examples

Experimental program
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Effect test

Embodiment 1

[0082] Embodiment 1: Synthesis of paclitaxel-linoleic acid small molecule prodrug (PTX-S-LA) bridged by monosulfide bridge

[0083] Add an appropriate amount of ethylene glycol into a 50mL three-neck flask, add a small amount of p-toluenesulfonic acid, heat to 110°C, slowly drip the oleic acid dissolved in toluene into the reaction flask, react for 2 hours, and monitor the reaction process by thin-layer chromatography , and then 20 mL of toluene was added to the system three times, and vacuum distillation was carried out to dryness. Dissolve the obtained product in 30mL of dichloromethane, add appropriate amount of thiodiacetic anhydride and a small amount of triethylamine, HOBT, EDCI, stir at room temperature for 24 hours, monitor the reaction process by thin layer chromatography, and purify by silica gel column chromatography An intermediate product is obtained. Finally, the intermediate product, EDCI, HOBt and DMAP were dissolved in 50 mL of anhydrous dichloromethane, ice-...

Embodiment 2

[0086] Example 2: Optimization of the preparation method of cucurbitacin B and paclitaxel prodrug co-loaded nano-cores (PCNPs)

[0087] In this example, three different methods and two different polymer materials, PEG-PCL and PEG-PLA, were used to prepare cucurbitacin B and paclitaxel prodrug co-loaded nano-cores, and the optimal preparation method was obtained through comparison.

[0088] Emulsion solvent evaporation method: Accurately weigh 6 mg of paclitaxel prodrug PTX-S-LA, 1 mg of cucurbitacin B, 60 mg of PEG-PCL or PEG-PLA, dissolve in 1 ml of acetone, pour the oil phase into a 4 mL rotor-stirred deionized In the water, the acetone was removed by rotary evaporation, and the uncoated free drug was removed by filtering the membrane to obtain the co-loaded nanoparticles of cucurbitacin B and paclitaxel prodrug.

[0089]Thin film dispersion method: Precisely weigh 6 mg of paclitaxel prodrug PTX-S-LA, 1 mg of cucurbitacin B, 60 mg of PEG-PCL or PEG-PLA, dissolve in 6 ml of a...

Embodiment 3

[0099] Example 3: Preparation and characterization of exosome membrane-coated cucurbitacin B and paclitaxel oxidized prodrug co-loaded biomimetic nanoparticles (EMPCs)

[0100] 60 mg PEG-PCL, 1 mg cucurbitacin B, and 6 mg paclitaxel oxidized prodrug were dissolved in 1 mL acetone, and then dropped into 4 ml deionized water stirred by a rotor. Organic solvents were removed by rotary evaporation, and unencapsulated free drugs were removed by membrane filtration. Collect the serum-free cell culture medium of MDA-MB-231 cells for 48 hours, centrifuge at 300g for 10 minutes to remove tumor cells, take the supernatant and centrifuge at 2000g for 10 minutes to remove dead cells, take the supernatant at 10,000g for 30 minutes to remove cell debris, and take the supernatant at 100,000 Centrifuge at g for 70 minutes, remove the supernatant, resuspend in PBS containing protease inhibitors, centrifuge at 100,000g for 70 minutes, remove the supernatant to obtain exosomes at the bottom. Af...

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Abstract

The invention belongs to the technical field of medicines, and relates to an exosome membrane-coated cucurbitacin B and oxidation-responsive antitumor prodrug co-loaded bionic nanoparticle, and an application thereof in the preparation of drugs for treating tumor metastasis diseases. The nanoparticle can ablate primary tumors and target circulating tumor cells so as to inhibit tumor metastasis. The exosome membrane-coated co-loaded bionic nanoparticle comprises 1-2 wt% of cucurbitacin B, 6-8 wt% of an oxidation-responsive antitumor prodrug, 60-70 wt% of a nano-carrier material, and the balanceof an exosome membrane, and the weight ratio of the cucurbitacin B to the oxidation-responsive antitumor prodrug is 1:4 to 1:8. The exosome membrane-coated cucurbitacin B and oxidation-responsive antitumor prodrug co-loaded bionic nanoparticle has an obvious effect of treating tumor metastasis, especially lung or liver metastasis of breast cancer, and can be used for preparing antitumor drugs.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a co-loaded biomimetic nanoparticle of exosome membrane-coated cucurbitacin B and an oxidation-responsive anti-tumor prodrug and its use in the preparation of drugs for treating tumor metastases. The nanoparticle can Ablation of primary tumors and targeting of circulating tumor cells to inhibit tumor metastasis. Background technique [0002] Metastatic breast cancer, also known as breast cancer metastases, is a stage of breast cancer, and distant metastasis is the cause of breast cancer death in 90% of breast cancer patients. Although the current clinical technology has made great progress, the therapeutic effect is still limited, and the five-year survival period of distant metastasis can only be improved by a few months at most. An important reason for this is that traditional chemotherapy drugs cannot target and eliminate circulating tumor cells in the blood. [0003] Nano-dr...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/575A61K31/337A61K9/50A61K47/34A61K47/46A61P35/00A61P35/04
CPCA61K9/5063A61K31/337A61K31/575A61K45/06A61K47/34A61P35/00A61P35/04A61K2300/00
Inventor 孙进何仲贵王开元叶皓
Owner SHENYANG PHARMA UNIVERSITY
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