LAUSR

Acute lung injury (ALI) is characterized by severe inflammation and damage to the lung air-blood barrier, resulting in respiratory function damage and life-threatening outcomes. Macrophage polarization plays an essential role in the occurrence, development, and outcome of ALI. As drug carriers, self-assembled DNA nanostructures can potentially overcome the drawbacks and limitations of traditional anti-inflammatory agents owing to their nontoxicity, programmability, and excellent structural control at the nanoscale. In this study, we proposed and constructed an siRNA and drug dual therapy nanoplatform to combat ALI. The nanoplatform consisted of a spermidine-assembled DNA tetrahedron and four mTOR siRNAs. Spermidine serves as a mediator of drug delivery vehicle synthesis and a drug that alters macrophage polarization. Both spermidine and siRNA exerted anti-inflammatory effects in vitro and in vivo by regulating the macrophage phenotype. More importantly, these factors exhibited a synergistic anti-inflammatory effect by promoting macrophage autophagy. For the first time, an anti-inflammatory dual therapy strategy that uses self-assembled DNA nanostructures as nontoxic, programmable delivery vehicles has been proposed and demonstrated through this work. Future work on utilizing DNA nanostructures for the treatment of noncancerous diseases such as ALI is highly promising and desirable. This article is protected by copyright. All rights reserved.