NAC-Grafted ROS-Scavenging Polymer Nanoparticles for\nModulation of Acute Lung Injury Microenvironment In Vivo

<i>N</i>-Acetyl cysteine (NAC) is an essential molecule\nthat boosts acute lung injury (ALI) defense via its direct antioxidant\ncapability. Nevertheless, the therapeutic use of NAC is limited due\nto its poor bioavailability and short half-life. In this study, NAC\nwas grafted to the polyurethane consisting of poly(propylene fumarate),\npoly(thioketal), and 1,6-hexamethylene diisocyanate (PFTU) to reduce\nexcessive oxidative stress and inflammatory factors in ALI. The NAC-grafted\npolymer nanoparticles (NPT@NPs) were prepared as a drug delivery system,\nwhich could effectively scavenge free radicals and reduce inflammation\nin vitro. The administration of NPT@NPs exhibited notable efficacy\nin ameliorating pulmonary edema, attenuating the presence of inflammatory\ncells, suppressing myeloperoxidase expression, diminishing the levels\nof pro-inflammatory cytokines, and reversing cell apoptosis in an\nALI model induced by lipopolysaccharide (LPS). The NPT@NPs demonstrated\nsignificantly better efficacy compared to the free NAC in mitigating\nthe deleterious effects of LPS on pulmonary tissue, thereby providing\nmore effective protection against pulmonary inflammation.