Acute lung injury (ARDS) is acute and diffuse inflammatory lung injury triggered by multiple factors such as pathogen infection, with a clinical mortality rate of up to 35–46%. Excessive inflammatory response is its most prominent pathological feature, so precise inhibition of inflammatory cascade is regarded as a key strategy for ARDS treatment. Currently, there is a lack of specific drugs for the cause of ARDS in clinical practice. Anti-inflammatory therapies such as glucocorticoids and IL-6 receptor antagonists are limited in efficacy and are accompanied by the risk of immunosuppression. In addition, the existing intervention methods face problems such as low drug bioavailability and outstanding off-target toxicity. Therefore, developing a new intervention platform that combines targeted delivery and multi-mechanism collaboration is an urgent need to break through the dilemma of ARDS drug treatment.

DNA nanocarriers have shown significant application potential in ARDS treatment with their advantages such as programmable targeting, gene-drug co-loading, and ROS clearance. The synthesis of DNA nanocarriers in traditional magnesium-containing ion systems faces challenges such as enzyme stability and functionalization in biological systems. The use of endogenous biological macromolecules to mediate the "non-traditional" assembly of DNA nanostructures and form composite functionalized nanocarriers provides new ideas for the precise treatment of ARDS. This strategy not only has significant advantages in targeted delivery, responsive release and multi-mechanism collaborative treatment, but also a potential path to promote the clinical transformation of DNA nanocarriers.