Brain-targeted drug delivery system with ferroptosis and immune activation cascade amplification effect

A drug delivery system and immune activation technology, applied in the field of new brain-targeted drug delivery system, can solve the problems of poor curative effect, less distribution of immune cells, and ineffective effects of glioma

Pending Publication Date: 2022-02-18
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the results of clinical studies have shown that the use of immune checkpoint inhibitors in the treatment of glioma is not very effective
Among them, the distribution of immune cells in the glioma area is less, which is the main reason for the poor efficacy of immune checkpoint inhibitors

Method used

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  • Brain-targeted drug delivery system with ferroptosis and immune activation cascade amplification effect
  • Brain-targeted drug delivery system with ferroptosis and immune activation cascade amplification effect
  • Brain-targeted drug delivery system with ferroptosis and immune activation cascade amplification effect

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Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0021] 1 Research method:

[0022] 1.1 Fe 3 o 4 -siPD-L1@M -BV2 Preparation and Characterization of Nanoparticles

[0023] 1.1.1 Fe 3 o 4 Screening with siPD-L1 feed ratio

[0024] Take six 0.6mL enzyme-free EP tubes, add 4 μL siPD-L1 (1OD siPD-L1 is dissolved in 125 μL DEPC water), 1.5 μL H 2 o 2, then add 1, 2, 3, 4 μL Fe in turn 3 o 4 For nanoparticles (5mg / mL), DEPC water was added to each tube to make up to 17 μL, pipet evenly with a pipette gun, and after standing for 1 hour, 3 μL of 5×RNA sample buffer was added sequentially for later use. Weigh 600mg of agarose powder, put it into a 100mL Erlenmeyer flask, add 40mL of prepared 0.5×TBE electrophoresis buffer, heat it in a microwave oven twice, 40s each time, take it out, and add 5μL gel red. Shake well, add it to the glass tank that has been set up while it is hot, and let it cool down for 30 minutes. Transfer the agarose gel to the electrophoresis tank, pull out the comb, add 0.5×TBE electrophoresis buffer u...

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Abstract

The invention relates to a novel brain-targeted drug delivery system, and particularly discloses a brain-targeted drug delivery system with ferroptosis and immune activation cascade amplification effects, in the presence of H2O2, siPD-L1 is connected to the surfaces of Fe3O4 nanoparticles through disulfide bonds, and a microglial cell membrane is used as a shell to construct siPD-L1-loaded bionic nanoparticles. The drug delivery system not only can silence the expression of PD-L1 in drug-resistant brain glioma cells and improve the immune microenvironment of the drug-resistant brain glioma, but also can promote the occurrence of ferroptosis, and finally forms a virtuous circle of mutual promotion between ferroptosis and immunotherapy to synergistically treat the drug-resistant brain glioma.

Description

technical field [0001] The invention relates to a novel brain-targeted drug delivery system, which can not only silence the expression of PD-L1 in drug-resistant glioma cells, improve the immune microenvironment of drug-resistant glioma, but also promote ferroptosis Finally, a virtuous cycle of mutual promotion between ferroptosis and immunotherapy is formed, and the synergistic treatment of drug-resistant glioma occurs. Background technique [0002] Glioma originates from the lesions of glial cells in the brain, and is the most common primary intracranial tumor, which is characterized by high malignancy, fast growth, and strong invasion. Common clinical manifestations are increased intracranial pressure, neurocognitive dysfunction, and seizures. The median survival time of patients is only 12-15 months, and only 3% of glioma patients survive for more than five years. The clinical standard treatment plan is combined with radiotherapy and temozolomide (TMZ) chemotherapy aft...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/52A61K9/51A61K47/46A61K31/7088A61P25/00A61P35/00
CPCA61K31/7088A61K47/52A61K9/5176A61P35/00A61P25/00
Inventor 刘道洲刘宝周四元纪奇峰成颖刘苗张邦乐
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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