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Integrin-targeted manganese-gadolinium hybrid bimetallic paramagnetic nanocolloids and their application in magnetic resonance imaging of neovascularization

A paramagnetic nano-integrin technology, applied in the field of medicine, can solve problems such as inability to effectively predict acute vascular events

Active Publication Date: 2017-01-18
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The results of the PROSPECT prospective clinical trial published in 2011 confirmed that traditional morphological indicators (such as thin fibrous cap, plaque load, and minimum lumen cross-sectional area) for predicting plaque rupture through intravascular ultrasound imaging cannot be effectively predicted. The occurrence of acute vascular events! The method successfully predicts only 18% of the actual incidence of acute vascular events due to plaque rupture over the next 2 years
However, further experiments showed that MnOL NC does not target integrin α, which is specifically expressed during neovascularization in atherosclerotic plaques. v beta 3 in vivo molecular imaging

Method used

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  • Integrin-targeted manganese-gadolinium hybrid bimetallic paramagnetic nanocolloids and their application in magnetic resonance imaging of neovascularization
  • Integrin-targeted manganese-gadolinium hybrid bimetallic paramagnetic nanocolloids and their application in magnetic resonance imaging of neovascularization
  • Integrin-targeted manganese-gadolinium hybrid bimetallic paramagnetic nanocolloids and their application in magnetic resonance imaging of neovascularization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Integrin α v beta 3 Preparation of targeted manganese-gadolinium hybrid bimetallic paramagnetic nanoparticles colloid

[0044] (1) Add 360ml of ethanol-water-n-hexane mixture into a 500ml round bottom flask, add 10g of manganese chloride tetrahydrate (MnCl 2 .4H 2 O) and 40g sodium oleate (TCI chemical), reacted at 80°C for 14 hours, then reacted at 25°C for 4 hours, washed with water, salt, Na 2 SO 4 After drying and rotary evaporating to dryness to remove the solvent, divalent manganese oleate is prepared, wherein, in the ethanol-water-n-hexane mixture, the volume ratio of ethanol, water and n-hexane is 4:5:9;

[0045] (2) Under a nitrogen atmosphere, suspend 10 g of divalent manganese oleate MnOL in 20 mL of sorbitan sesquioleate as a concentrate, and add phospholipids at 141 MPa and 4 °C Surfactant, so that its final concentration is 0.02g / ml, fully mixed, described phospholipid surfactant comprises 0.1 mol% menadione dimethazine sulfite-polyethylene ...

Embodiment 2

[0047] Example 2 Integrin α v beta 3 Preparation of targeted manganese-gadolinium hybrid bimetallic paramagnetic nanoparticles colloid

[0048] (1) Add 360ml of ethanol-water-n-hexane mixture into a 500ml round bottom flask, add 10g of manganese chloride tetrahydrate (MnCl 2 .4H 2 O) and 40g sodium oleate (TCI chemical), reacted at 80°C for 14 hours, then reacted at 25°C for 4 hours, washed with water, salt, Na 2 SO 4 After drying and rotary evaporating to dryness to remove the solvent, divalent manganese oleate was prepared, wherein, in the ethanol-water-n-hexane mixture, the volume ratio of ethanol, water and n-hexane was 4:5:9.

[0049] (2) Under a nitrogen atmosphere, suspend 10 g of divalent manganese oleate MnOL in 20 mL of polysorbate 80 as a concentrate, and add a phospholipid surfactant at 141 MPa and 4 °C to make the final concentration 0.02g / ml, fully mixed, described phospholipid surfactant comprises the phosphatidylethanolamine of the integrated polyethylene ...

Embodiment 3

[0051] Example 3 Application of manganese-gadolinium hybrid bimetallic paramagnetic nanoparticles in magnetic resonance imaging

[0052] 1. Optimization of MRI parameters:

[0053] In order to optimize the parameters of magnetic resonance imaging, the present invention has previously prepared a v beta 3 The manganese-gadolinium hybrid bimetallic paramagnetic nanoparticles (MnOL-Gd) of the specific biomolecules are used for the following research, the preparation method of MnOL-Gd is the same as that of Examples 1 and 2, but the phospholipid surfactant used does not contain horse Integral polyethylene glycol 2000 phosphatidylethanolamine modified by aryl, amino, sulfhydryl or carboxyl groups and targeting α v beta 3 specific biomolecules.

[0054] All MRIs were performed on a Philips clinical 3.0T magnetic resonance scanner, and standard birdcage coils were used in in vitro experiments. According to the method of the present invention, MnOL-Gd NCs with different concentrat...

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Abstract

The invention discloses an integrin targeted MnOL-Gd hybrid bimetallic paramagnetic nanocolloid (alpha v beta 3-MnOL-Gd NC) and application in magnetic resonance imaging (MRI) of angiogenesis. The alpha v beta 3-MnOL-Gd NC provided by the invention is obtained by coupling alpha v beta 3 targeted specific biomolecules of polyethylene glycol 2000 integrated phosphatidyl ethanolamine to the surfaces of MnOL-Gd hybrid bimetallic paramagnetic nanoparticles. Research shows that, the alpha v beta 3-MnOL-Gd NC is effective in imaging of angiogenesis, and can generate specific angiogenesis imaging high signal contrast 2 hours after injection. Therefore, the alpha v beta 3-MnOL-Gd NC disclosed by the invention can be used for T1 weighted MR molecular imaging of angiogenesis, and is free of obvious allergic reaction side effect, thus providing a new technological means for magnetic resonance imaging of angiogenesis.

Description

technical field [0001] The present invention relates to an integrin-targeted nanocolloid and its application, in particular to an integrin-targeted nanocolloid coupled with α v beta 3 (α v beta 3 -integrin) integrin-targeted hybrid manganese-gadolinium nanocolloid and its application in magnetic resonance imaging of neovascularization, the invention belongs to the technical field of medicine. Background technique [0002] Neovascularization is a key microanatomical feature in the development of atherosclerotic plaques and plays a key role in the expansion of vulnerable plaques and the rupture of plaques. The results of the PROSPECT prospective clinical trial published in 2011 confirmed that traditional morphological indicators (such as thin fibrous cap, plaque load, and minimum lumen cross-sectional area) for predicting plaque rupture through intravascular ultrasound imaging cannot be effectively predicted. The occurrence of acute vascular events! The successful predict...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/12A61K49/18
Inventor 申宝忠王可铮吴丽娜
Owner HARBIN MEDICAL UNIVERSITY
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