A nanosystem targeting tissue inhibitor of metalloproteinase-1 for continuous spatiotemporal idiopathic pulmonary fibrosis therapy

  • Nat Commun. 2026 Jan 19;17(1):1694. doi: 10.1038/s41467-026-68398-0.
Chuyu Li  #  1 ,  Guihong Lu  #  2 ,  Hanlin Chen  1 ,  Chenguang Wang  1 ,  Zhongjie Wang  1 ,  Ruiqi Ming  1 ,  Shujun Liu  1 ,  Lili Huang  3  4
Affiliations
  • 1. School of Medical Technology, Beijing Institute of Technology, Beijing, PR China.
  • 2. Center for Child Care and Mental Health (CCCMH), Shenzhen Children's Hospital, Shenzhen, PR China.
  • 3. School of Medical Technology, Beijing Institute of Technology, Beijing, PR China. [email protected].
  • 4. Tangshan Research Institute, Beijing Institute of Technology, Tangshan, PR China. [email protected].
  • # Contributed equally.
PMID: 41554719 DOI: 10.1038/s41467-026-68398-0
Abstract

Idiopathic pulmonary fibrosis (IPF), a progressive, life-threatening disease marked by excessive Collagen deposition, severe tissue injury, and dysregulated oxidative stress, poses a major threat to human health. Despite clinical advances, current therapies have limited anti-fibrotic efficacy. Here we show a reactive oxygen species (ROS)-responsive nanosystem targeting tissue inhibitor of metalloproteinase-1 (TIMP-1) for spatiotemporally precise IPF treatment. Anti-TIMP-1 antibodies (aT) are conjugated to mesenchymal stem cell-derived Exosomes (Mexo) via ROS-cleavable phenylboronic acid ester linkers (cl), yielding Mexo-cl-aT. Following intratracheal administration, cl linkers are selectively cleaved by elevated ROS in the IPF microenvironment, enabling ROS scavenging while releasing Mexo and aT to mediate tissue repair and Collagen degradation, respectively. We demonstrate that a single dose of Mexo-cl-aT exerts robust therapeutic efficacy against IPF in a bleomycin-induced mouse model of advanced-stage fibrosis, thereby validating this nanosystem as a safe and efficient candidate for next-generation IPF therapies.

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