Hepatic endoplasmic reticulum-derived nanodiscs for broad-spectrum drug detoxification.
Lei Sun, Kailin Feng, Dean Bai, Yiyan Yu, Wei-Ting Shen, Jiayuan Alex Zhang, Ronnie H Fang, Weiwei Gao, Liangfang Zhang
Author Information
Lei Sun: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, 92093, USA.
Kailin Feng: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, 92093, USA.
Dean Bai: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, 92093, USA.
Yiyan Yu: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, 92093, USA.
Wei-Ting Shen: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, 92093, USA.
Jiayuan Alex Zhang: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, 92093, USA.
Ronnie H Fang: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, 92093, USA.
Weiwei Gao: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: w5gao@ucsd.edu.
Liangfang Zhang: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: zhang@ucsd.edu.
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.
