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

## TL;DR

This paper introduces a new nanosystem that targets TIMP-1 to treat IPF by scavenging harmful ROS and promoting tissue repair with a single dose.

## Contribution

A ROS-responsive nanosystem that combines anti-TIMP-1 antibodies and exosomes for spatiotemporal IPF therapy.

## Key findings

- The nanosystem effectively scavenges ROS in the IPF microenvironment.
- A single dose of Mexo-cl-aT showed robust therapeutic efficacy in a mouse model of IPF.
- The treatment promotes collagen degradation and tissue repair in advanced-stage fibrosis.

## 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.

Here the authors developed a ROS-responsive nanosystem that scavenges ROS and spatiotemporally releases anti-TIMP-1 antibodies and mesenchymal stem cell-derived exosomes, driving collagen degradation and tissue repair, and achieving strong anti-fibrotic effects with a single dose.