ROS-responsive microneedles loaded with integrin avβ6-blocking antibodies for the treatment of pulmonary fibrosis.

Abstract

Pulmonary fibrosis (PF) is a fibrotic interstitial pneumonia with poor prognosis and limited treatment methods. Inhibition of integrin αVβ6 expression could prevent pulmonary fibrosis, however, a phase II clinical trial of αVβ6-blocking antibody treating PF stopped prematurely due to low bioavailability and toxic side effects of systematic administration. Here, we describe a micro-invasive percutaneous transthoracic and hydrogen peroxide-responsive microneedle composed of degradable gel for smart delivery of integrin αvβ6-blocking antibody which has the advantages of rapid response, excellent biocompatibility, protection of bioactivity, high tissue permeation and specific targeting to lesions. This microneedle could partially release integrin αvβ6-blocking antibodies when exposed to hydrogen peroxide generated during PF, thus reducing activation of the pro-fibrotic factor TGF-β1 from its latent precursor and showing excellent therapeutic efficacy for PF.