Application of nano-drug targeting ferroptosis in treatment of acute kidney injury

A kind of acute kidney injury, nanotechnology, applied in the directions of non-active ingredients medical preparations, medical preparations containing active ingredients, drug combinations, etc., can solve problems such as incomplete prevention or treatment, reduce mitochondrial dysfunction, The effect of reducing accumulation and strong stability

Pending Publication Date: 2022-07-05
THE FOURTH AFFILIATED HOSPITAL OF ZHEJIANG UNIV SCHOOL OF MEDICINE
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  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, clinical studies using necrosis- or apoptosis-specific inhibitors have failed to completely prevent or treat AKI

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  • Application of nano-drug targeting ferroptosis in treatment of acute kidney injury
  • Application of nano-drug targeting ferroptosis in treatment of acute kidney injury
  • Application of nano-drug targeting ferroptosis in treatment of acute kidney injury

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Embodiment Construction

[0031] The technical solutions of the present invention will be described in further detail below with reference to the accompanying drawings. It should be noted that the specific embodiments are only detailed descriptions of the present invention and should not be regarded as limitations of the present invention.

[0032] All instruments, solvents, etc. in the following examples can be obtained through commercial channels, where 1M=1 mol / L.

[0033] 1.1 Synthesis of GGP NPs

[0034] The preparation of GGP NPs (ie gallium gallate polyvinylpyrrolidone nanoparticles) includes the following steps:

[0035] 340 mg of polyvinylpyrrolidone (PVP) molecules (Sigma-Aldrich, Cat#9003-39-8) were added to 45 mL of ultrapure water and stirred for 30 min;

[0036] Subsequently, Ga(NO 3 ) 3 (Sigma-Aldrich, Cat#289892) ultrapure aqueous solution (10 mL, 15 mg / mL);

[0037] After stirring for 6h, 5mL of gallic acid (Alfa Aesar, Cat#149-91-7) aqueous solution (10mg / mL) was added dropwise to...

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Abstract

The invention discloses an application of a ferroptosis-targeting nano-drug in treatment of acute kidney injury. Gallium gallate polyvinylpyrrolidone nanoparticles (GGP NPs) are synthesized in the invention, and the nanoparticles have strong stability, excellent biocompatibility and effective iron substitution ability. The GGP NPs has the advantages that accumulation of free iron in cells and mitochondrial dysfunction are reduced, ferroptosis-mediated phenotypes including lipid peroxidation, NADPH (nicotinamide adenine dinucleotide phosphate) and glutathione levels and glutathione peroxidase 4 activity are inhibited, and accordingly the HK-2 cell ferroptosis induced by cis-platinum can be obviously inhibited. The GGP NPs treatment can significantly improve renal tubule injury and mitochondrial injury caused by cisplatin treatment or ischemia reperfusion injury. The GGP NPs synthesized by the invention may be an effective and promising candidate drug for AKI treatment.

Description

technical field [0001] The invention specifically relates to the application of nanomedicine targeting ferroptosis in the treatment of acute kidney injury. Background technique [0002] Acute kidney injury (AKI) is a group of clinical syndromes that refers to sudden (within 1-7 days) and sustained (>24h) sudden decline in renal function, manifested by azotemia, water-electrolyte and acid-base balance, and systemic Various system symptoms may be accompanied by oliguria (<400ml / 24h or 17ml / h) or anuria (<100ml / 24h). [0003] AKI can be caused by a variety of factors, such as nephrotoxic drugs, ischemia, and urinary tract obstruction. Although AKI has been studied by many experts and scholars in the past few decades, the complex pathophysiology of AKI has not been fully understood, and the exact therapy to prevent or treat AKI has not been identified. Multiple cell death pathways, including necrosis and apoptosis, have been previously reported to be involved in AKI. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K47/32A61K31/192A61K33/24A61P13/12
CPCA61K9/146A61K31/192A61K33/24A61P13/12A61K2300/00
Inventor 林伟强李杨杨张云敬谢锡绍苏心婉
Owner THE FOURTH AFFILIATED HOSPITAL OF ZHEJIANG UNIV SCHOOL OF MEDICINE
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