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

  • Biomaterials. 2025 Feb 12:318:123188. doi: 10.1016/j.biomaterials.2025.123188.
Lei Sun  1 ,  Kailin Feng  1 ,  Dean Bai  1 ,  Yiyan Yu  1 ,  Wei-Ting Shen  1 ,  Jiayuan Alex Zhang  1 ,  Ronnie H Fang  1 ,  Weiwei Gao  2 ,  Liangfang Zhang  3
Affiliations
  • 1. 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.
  • 2. 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: [email protected].
  • 3. 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: [email protected].
PMID: 39954312 DOI: 10.1016/j.biomaterials.2025.123188
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.

Keywords
Cellular nanodisc; Cytochrome enzyme; Detoxification; Drug overdose; Nanomedicine.
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