Composite nanozymes surface-coated with thioketal and di-sulfide-containing polyurethane for acute lung injury treatment

Acute lung injury (ALI) is a prevalent and life-threatening condition lacking specific and effective treatments. To mitigate the inflammatory response within the ALI microenvironment, in this study a novel polyurethane (PCLSTU) was synthesized by using di-sulfide diisocynate and thioketal (TK) chain extender as the hard segment, which was used to prepare ROS-responsive anti-inflammatory nanoparticles (PCLSTU@PDA-CeO₂ NPs) loaded with polydopamine (PDA)-ceria NPs (CeO₂ NPs). In vitro studies demonstrated that the PCLSTU@PDA-CeO₂ NPs with a size of 400 nm exhibited enhanced ROS-scavenging activity under near-infrared (NIR) irradiation. Therapeutic efficacy was validated in a lipopolysaccharide (LPS)-induced ALI mouse model via nebulization inhalation and intravenous administration in vivo, where NIR irradiation significantly reduced lung edema and inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF). Comparatively, tail vein injection showed better therapeutic efficacy than the nebulization inhalation, highlighting their promise as a novel strategy for ALI treatment.