IL-13 modified gadolinium chelate containing liposome targeted magnetic resonance imaging contrast agent and preparation method and application thereof

A technology of magnetic resonance imaging and contrast agent, applied in the field of medical imaging

Active Publication Date: 2016-10-05
麦克斯韦磁谷科学技术(清远)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

but extruded through the membrane up to 20 times during liposome preparation

Method used

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  • IL-13 modified gadolinium chelate containing liposome targeted magnetic resonance imaging contrast agent and preparation method and application thereof
  • IL-13 modified gadolinium chelate containing liposome targeted magnetic resonance imaging contrast agent and preparation method and application thereof
  • IL-13 modified gadolinium chelate containing liposome targeted magnetic resonance imaging contrast agent and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0038] Example 1 Preparation of IL-13-liposomes-Gd-DTPA.

[0039] Dipalmitoylphosphatidylcholine 80mg, distearoylphosphatidylethanolamine-polyethylene glycol 13mg, cholesterol 20mg and distearoylphosphatidylethanolamine-polyethylene glycol-maleimide cross-linked product 10mg ( The molar ratio is 10:5:5:0.5) dissolved in 40mL of methanol chloroform (the volume ratio of the two is 1:1) mixed solvent, the solvent is volatilized under the condition of rotating vacuum at 40°C to form a film, and the film is dried in nitrogen 10-20min, and then sealed in a desiccator at 4°C for 14-16h. Gadopentetate dimeglumine was added to the container containing the liposome film, and with the assistance of ultrasound, the liposome film encapsulated the MRI contrast agent to form multilamellar liposomes containing the MRI contrast agent. The liposome was frozen and thawed four times at -80° C., then squeezed through a polycarbonate membrane with a pore size of 200 nm by nitrogen gas four times, ...

Embodiment 2

[0043] Example 2 IL-13-liposomes-Gd-DTPA can cross the blood-brain barrier

[0044] To demonstrate that IL-13-modified gadolinium-containing liposome-containing liposome-targeted magnetic resonance imaging contrast agent IL-13-liposomes-Gd-DTPA can cross the blood-brain barrier, we selected normal nude mice without brain cancer Experiment with the model. The results showed that after injection of Magnevist Gd-DTPA in nude mice without brain cancer for 30 minutes, the signal-to-noise ratio (SNR) of the pituitary gland in nude mice increased by 25%, on the contrary, the SNR of the brain parenchyma remained constant. It indicated that the contrast agent of Magnevist could not pass through the blood-brain barrier of live nude mice to reach the brain parenchyma. In contrast, after injecting IL-13-liposomes-Gd-DTPA to nude mice without brain cancer for 30 minutes, not only the signal-to-noise ratio of the pituitary gland in the nude mice increased by 20%, but also the signal-to-no...

Embodiment 3

[0045] Example 3 Targeting of IL-13-liposomes-Gd-DTPA

[0046] IL-13-modified liposome MRI contrast agent (FITC-IL-13-liposomes-Gd-DTPA) and IL-13-free liposome contrast agent (FITC-liposomes -Gd-DTPA), in order to observe the effect of contrast agent uptake by cells in the cytoplasm of glioma U251 and GSC T3691 cells, we did a cell uptake experiment. The histological results of biological cells showed that more IL-13-modified FITC-IL-13-liposomes-Gd-DTPA was observed in the cytoplasm of glioma stem cells GSC T3691. It suggested that IL-13 has a high affinity with the IL-13Rα2 receptor in GSC T3691 cells, which can promote the uptake of IL-13-liposomes-Gd-DTPA by specific tumor cells to the greatest extent.

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Abstract

The invention discloses an IL-13 modified gadolinium chelate containing liposome targeted magnetic resonance imaging contrast agent and a preparation method and application thereof. The contrast agent is gadolinium chelate encapsulated liposome, and the surface of the liposome is modified by IL-13. The preparation method of the IL-13 modified gadolinium chelate containing liposome targeted magnetic resonance imaging contrast agent comprises the steps that a liposome film is firstly prepared; then gadolinium chelate is added into a container containing the liposome film; the gadolinium chelate is wrapped by the liposome film with the assistance of ultrasonic waves to form gadolinium chelate containing multilamelar liposome; the surface of the gadolinium chelate encapsulated multilamelar liposome is modified by thiolated IL-13. The contrast agent can penetrate through a blood brain barrier to be transferred to a tumor diseased region and be specifically bound with the tumor diseased region. Therefore, the contrast agent has targeting ability, can detect a tumor focus smaller than 2 mm and can be used for early detection of tumors.

Description

technical field [0001] The invention belongs to the technical field of medical imaging, and in particular relates to an IL-13-modified gadolinium-containing chelate liposome targeting magnetic resonance imaging contrast agent and a preparation method and application thereof. Background technique [0002] Currently, the technologies used for tumor diagnosis mainly include computed tomography (CT), positron emission computed tomography (PET), optical imaging, and ultrasound imaging. Because magnetic resonance imaging (MRI) has no ionizing radiation, and can perform more accurate positioning and quantitative analysis of deep tissues with the help of contrast agents, it has become one of the commonly used clinical detection and diagnosis methods. [0003] Bowel cancer, also known as colorectal cancer, which occurs in the colon or rectum, is the third most common cancer diagnosed in the United States and the third leading cause of cancer deaths. The danger is that once liver met...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18A61K49/14
Inventor 杨庆宪
Owner 麦克斯韦磁谷科学技术(清远)有限公司
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