Hepatic endoplasmic reticulum-derived nanodiscs for broad-spectrum drug detoxification.

Abstract

Drug overdose is a pressing global public health challenge, with current detoxification treatments often lacking the broad-spectrum efficacy needed for emergency applications. Inspired by the unique advantages of cell membrane-derived nanodiscs (CNDs), including their compact size, rapid distribution, and preservation of native cell membrane functions, we developed endoplasmic reticulum (ER)-derived nanodiscs (ER-NDs) from the ER membranes of mouse hepatic cells for broad-spectrum drug detoxification. ER-NDs retain natural cytochrome P450 (CYP) enzymes, enabling effective detoxification of three model drugs: bupropion, haloperidol, and propranolol. Cell-based assays demonstrated ER-NDs' ability to mitigate drug-induced cytotoxicity, reduce oxidative stress, and restore antioxidant defenses. In mouse models of drug intoxication, ER-ND treatment significantly improved survival rates and alleviated drug-induced oxidative damage. Importantly, ER-NDs showed no evidence of acute toxicity in vivo. These findings underscore the potential of ER-NDs as a versatile platform for broad-spectrum drug detoxification and as a promising tool for managing drug intoxication in emergency and clinical settings.