Prolonged Retention of Albumin Nanoparticles Alleviates Renal Ischemia-Reperfusion Injury through Targeted Pyroptosis.

Abstract

Acute kidney injury (AKI) represents a prevalent and complex clinical event, characterized by irreversible damage to renal tubular epithelial cells and high intensive care unit (ICU) admission rates and mortality. The kidneys are highly susceptible to oxidative stress, inflammation, pyroptosis, and programmed cell death. Pyroptosis poses a significant risk, exacerbating the damage and inflammation of renal tubular cells. Disulfiram (DSF), an FDA-approved medication for alcohol cessation, inhibits the pyroptotic pore-forming protein Gasdermin-D (GSDMD), positioning it as a potential solution for emergency relief against an inflammatory response. However, current obstacles include poor water solubility, rapid metabolism, and off-target effects. Inspired by this discovery, bovine serum albumin (BSA), which has already entered clinical application, has been utilized to produce safe and long-lasting nanoparticles (BSA@DSF NPs), addressing the challenges posed by DSF's physicochemical properties. By targeting the GSDMD protein, the potent pro-inflammatory effects of pyroptosis were mitigated, leading to the alleviation of AKI induced by ischemia-reperfusion injury. This research offers a straightforward and efficient concept for treating AKI, potentially enhancing the transition to clinical practice.