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Novel nano-molecular MRI targeted thrombus contrast agent and preparation method thereof

A technology of nano-molecules and contrast agents, applied in nano-magnetism, nano-technology, nano-technology, etc., can solve the problems of ineffective detection of thrombus shedding site, unknown source of thrombus embolism, specificity of thrombus detection, etc.

Pending Publication Date: 2021-01-22
广州市番禺区中心医院
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Problems solved by technology

[0003] There are many defects in the existing technology: First, even with the best imaging technology at present, the source of thromboembolism in 30%-40% of myocardial infarction is still unknown, and the current imaging method cannot effectively detect the shedding site of the thrombus
Second is the specificity of thrombus detection
Current imaging methods to detect thrombus are mainly indirect methods and cannot directly detect blood clots

Method used

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  • Novel nano-molecular MRI targeted thrombus contrast agent and preparation method thereof

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preparation example Construction

[0020] A novel nano-molecular MRI targeted thrombosis contrast agent and a preparation method thereof, which includes a contrast agent, and the preparation method of the contrast agent comprises the following steps:

[0021] Step 1: Expression and purification of human ferritin modified by KGDS polypeptide

[0022] Through the method of genetic engineering, the N-terminal of the human ferritin H subunit is connected with the KGDS polypeptide segment to obtain KGDS-Fn, which has the ability to target and activate the platelet membrane protein GPIIb / IIIa, and transform competent Escherichia coli E. A strain expressing KGDS-Fn was obtained from coli, and after protein expression was induced by isopropylthiogalactoside (IPTG), high-expression and highly purified KGDS-Fn was obtained, using sodium dodecyl sulfate-polyacrylamide gel Electrophoresis (SDS-PAGE) to verify the product protein;

[0023] Step 2: Loading of Gd-DOTA by KGDS-modified ferritin nanocarrier (KGDS-FRT)

[0024...

specific Embodiment approach

[0032] Specific implementation methods: (see figure 1 )

[0033] (1) Introducing KGDS targeting the highly expressed GPIIb / IIIa receptors of activated platelets into the shell surface structure of the apoferritin nanocarrier to obtain specific enrichment and active targeted delivery of activated platelets.

[0034] (2) Utilizing the acid-base properties of Apoferritin, Gd-DOTA is embedded in the carrier to endow the nano-carrier with visualization characteristics, and the distribution and location of activated platelets are monitored by MRI molecular imaging method.

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Abstract

The invention relates to a novel nano-molecular MRI targeted thrombus contrast agent and a preparation method thereof. The novel nano-molecular MRI targeted thrombus contrast agent comprises the contrast agent. The preparation method for the novel nano-molecular MRI targeted thrombus contrast agent comprises the following steps of: carrying out expression and purification of human ferritin modified by KGDS polypeptides, connecting a KGDS polypeptide segment to the N terminal of the H subunit of the human ferritin to obtain KGDS-Fn, and converting competence E. coli to obtain a bacterial straincapable of expressing KGDS-Fn; S2: loading Gd-GOTA by a ferritin nano-carrier (KGDS-FRT) modified by the KGDS; S3: testing the fundamental representation of the multifunctional ferritin nano-carrier;and S4: detecting the relevant properties of the multifunctional ferritin nano-carrier. Compared with the prior art, the invention has the advantages that the novel (Apoferritin) nono-carrier with efficient targeting and biocompatibility is prepared, the MRI contrast agent is transmitted, and targeted MRI monitoring of activated platelets is realized.

Description

technical field [0001] The invention relates to the field of biological materials, in particular to a novel nano-molecule MRI targeting thrombosis contrast agent and a preparation method thereof. Background technique [0002] Thrombosis of atherosclerotic plaque is an increasingly serious threat to human health. It is very harmful. In normal blood circulation, platelets are in a resting state. It is in the activated state, which is the central link in the occurrence and development of thrombus. Therefore, imaging of activated platelets is an effective way to diagnose early thrombus formation. At present, thrombus imaging mainly uses ultrasound, CT, MRI, etc. in clinical practice. Although these methods are initially successful in clinical practice, there are still many defects. The development of suitable MRI molecular targeting imaging contrast agents is a very important topic. [0003] There are many defects in the existing technology: first, even with the best imaging te...

Claims

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Application Information

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IPC IPC(8): A61K49/10A61K49/14B82Y25/00
CPCA61K49/108B82Y25/00A61K49/14
Inventor 郭惠庄钟陶
Owner 广州市番禺区中心医院
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