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Acoustic radiation force enhanced inflammatory cell induced atherosclerosis biomimetic microbubble complex enriching and targeting system

A technology for atherosclerosis and inflammatory cells, applied in the field of medical imaging, can solve the problems of poor contrast imaging and targeted therapy, failure to achieve diagnosis and treatment, etc.

Active Publication Date: 2018-01-26
SHANDONG UNIV QILU HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, only the loads on the surface of MBs close to the tube wall can bind to the tube wall or the targets on the tube wall. Therefore, the current contrast imaging is achieved only by the movement of MBs in the flow field and the active target binding force of the loads on the MB surface. The effect of targeted therapy is poor, and the expected diagnostic and therapeutic purposes cannot be achieved

Method used

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  • Acoustic radiation force enhanced inflammatory cell induced atherosclerosis biomimetic microbubble complex enriching and targeting system
  • Acoustic radiation force enhanced inflammatory cell induced atherosclerosis biomimetic microbubble complex enriching and targeting system
  • Acoustic radiation force enhanced inflammatory cell induced atherosclerosis biomimetic microbubble complex enriching and targeting system

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preparation example Construction

[0047] In yet another specific embodiment of the present invention, a method for preparing a biomimetic microbubble complex induced by inflammatory cells to atherosclerosis comprises the following steps:

[0048] S1. Using distearoylphosphatidylcholine (DSPC), distearoylphosphatidylethanolamine (DSPE)-polyethylene glycol 2000 and biotinylated DSPE-polyethylene glycol 2000 as membrane materials, through the film- Hydration method to prepare ultrasonic microbubble contrast agent;

[0049] S2. Inject biologically inert gas into the ultrasonic microbubble contrast agent, and vibrate to prepare ultrasonic lipid microbubbles;

[0050] S3. Linking ultrasonic lipid microbubbles and CD11b ligands through biotin-streptomycin reaction to prepare CD11b targeting microbubbles;

[0051] S4. CD11b-targeted microvesicles and inflammatory cells construct inflammatory cell-CD11b-microvesicle complexes through antigen-antibody reactions, that is, inflammatory cell-induced atherosclerosis biomim...

Embodiment 1

[0064] Such as figure 2 As shown, it is an acoustic radiation force generation system, including: free-wave converter, radio frequency power amplifier, and focused ultrasound probe and connecting wires. The experimental steps are as follows:

[0065] Step 101, connect arbitrary waveform generator, RF power amplifier and probe (focus probe, 2.25MHz)

[0066] Step 102, according to the experiment, we put a 2.25MHz focused ultrasound probe (focal length 4.25cm) into the customized test water tank, the focal length is 4.25cm, and the focal area is 1.00mm 2 , Adjust the value, 2.25MHz, 100mvpp, RF50-80%, the peak negative pressure is 0.11MPa-1.36Mpa.

[0067] Step 103, preparing ultrasonic lipid microbubbles according to the above method. The microbubbles are measured by Malvern Particle Size and have an average diameter of 1-2 microns.

[0068] Step 104, static fluid system, injecting microbubbles into fluid tubes or parallel plates, and static after filling.

[0069] Step 1...

Embodiment 2

[0084] The neutrophils in the peripheral blood of ApoE- / - mice were separated by percoll density gradient. According to the method described above, perfluorinated polyfluorides were prepared by thin film hydration method with distearoylphosphatidylcholine (DSPC), distearoylphosphatidylethanolamine (DSPE)-polyethylene glycol and biotinylated DSPE-polyethylene glycol. Propane lipid microbubbles, microbubble particle size 1-2 microns. Using the biotin-streptomycin reaction to link the CD11b ligand to the microvesicles, and then construct the neutrophil-CD11b-microvesicle complex through the antigen-antibody reaction, such as figure 1 shown.

[0085] The complex was injected into ApoE- / - mice fed with high fat for 12 weeks via the tail vein as a bolus, and the 16MHz small animal ultrasonic probe was placed on the body surface to scan the aortic arch. A 2.25MHz focused ultrasound probe is used to generate acoustic radiation force and is placed next to the imaging probe. After the ...

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Abstract

The invention discloses an acoustic radiation force enhanced inflammatory cell induced atherosclerosis biomimetic microbubble complex enriching and targeting system. An inflammatory cell induced atherosclerosis biomimetic microbubble complex comprises a CD11b targeting microbubble and an inflammatory cell which are interconnected. The microbubble-CD11b-inflammatory cell complex is successfully constructed by using the connection of a modified microbubble surface group and an activated CD11b molecule on the surface of the inflammatory cell, so the combination of the microbubble with an inflammatory cell in blood through the special CD11b molecule on the inflammatory cell is ensured, and the activation site of the inflammatory cell and blood vessel endothelial adherence and migration is reserved; and the acoustic radiation force is used to enhance the local concentration and the targeting adherence effect of the complex to realize the in-vivo display of the endothelial inflammatory activity in the atherosclerotic part in order to simulate the pathophysiological process of the inflammatory cell induced atherosclerosis, so the system has a great bionic meaning.

Description

technical field [0001] The invention belongs to the field of medical imaging, and in particular relates to a system and a method for enhancing the enrichment and targeting of atherosclerotic bionic microbubble complexes induced by inflammatory cells by acoustic radiation. Background technique [0002] Cardiovascular and cerebrovascular diseases have become the number one killer that endangers the health of Chinese residents. In recent years, studies have confirmed that the rupture of atherosclerotic plaques and secondary thrombosis are important causes of acute cardiovascular and cerebrovascular events. Early identification and intervention of atherosclerosis has become a key factor in the 21st century. It is an important content to improve people's health level in our country. [0003] Atherosclerosis is a systemic inflammatory disease involving the whole body. Existing studies have shown that inflammatory cells including monocytes, neutrophils, and macrophages are involved...

Claims

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Application Information

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IPC IPC(8): A61K49/22A61K47/68A61K47/54G01N29/06
Inventor 张鹏飞严飞李飞毛洋
Owner SHANDONG UNIV QILU HOSPITAL
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