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Gadolinium-containing chelate liposome-targeted magnetic resonance imaging contrast agent modified by il-13 and its preparation method and application

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

Active Publication Date: 2019-08-09
麦克斯韦磁谷科学技术(清远)有限公司
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  • 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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  • Gadolinium-containing chelate liposome-targeted magnetic resonance imaging contrast agent modified by il-13 and its preparation method and application
  • Gadolinium-containing chelate liposome-targeted magnetic resonance imaging contrast agent modified by il-13 and its preparation method and application
  • Gadolinium-containing chelate liposome-targeted magnetic resonance imaging contrast agent modified by il-13 and its preparation method and application

Examples

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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 injecting the nude mice without brain cancer with Magnevist Gd-DTPA for 30 minutes, the signal-to-noise ratio (SNR) of the pituitary gland in nude mice increased by 25%, on the contrary, the signal-to-noise ratio 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 ...

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-containing chelate liposome targeted magnetic resonance imaging contrast agent, a preparation method and application thereof. The contrast agent is a liposome encapsulating a gadolinium chelate, and the surface of the liposome is modified with IL-13. Its preparation method is to prepare the liposome film first, then add the gadolinium chelate into the container containing the liposome film, and with the assistance of ultrasonic waves, the liposome film wraps the gadolinium chelate to form a gadolinium-containing chelate multilamellar liposomes; the surface of multilamellar liposomes encapsulating gadolinium chelates was modified with thiolated IL‑13. The contrast agent of the present invention can pass through the blood-brain barrier, deliver to tumor lesion sites and specifically bind to it. Therefore, this contrast agent is targeted, can detect tumor lesions smaller than 2mm, 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 Patents(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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