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
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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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