Open AccessInhaled Pro‐Efferocytic Nanozymes Promote Resolution of Acute Lung Injury
Author(s) -
Ji Haiying,
Zhang Chengmi,
Xu Fengying,
Mao Qianyun,
Xia Ran,
Chen Muqiao,
Wang Wei,
Lv Shunan,
Li Weiwei,
Shi Xueyin
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202201696
Subject(s) - efferocytosis , inflammation , apoptosis , reactive oxygen species , macrophage , medicine , microbiology and biotechnology , phagocytosis , sepsis , immunology , cancer research , chemistry , biology , in vitro , biochemistry
Acute lung injury (ALI) is a significant contributor to the morbidity and mortality of sepsis. Characterized by uncontrolled inflammation and excessive inflammatory cells infiltration in lung, ALI has been exacerbated by impaired efferocytosis (clearance of apoptotic cells by macrophages). Through specific receptor recognition and activation of downstream signaling, efferocytic macrophages promote resolution of inflammation by efficiently engulfing dying cells, avoiding the consequent release of cellular inflammatory contents. Here, inspired by the intrinsic recovery mechanism of efferocytosis, an apoptotic cell membrane (ACM) coated antioxidant nanozyme (AOzyme) is engineered, thus obtaining an inhalable pro‐efferocytic nanozyme (AOzyme@ACM). Notably, AOzyme@ACM can efficiently increase apoptotic cell removal by combing enhanced macrophages recognition of “eat me” signals through apoptotic body mimicking and scavenge of intracellular excessive reactive oxygen species (ROS), a significant barrier for efferocytosis. AOzyme@ACM can significantly inhibit inflammatory response, promote pro‐resolving (M2) phenotype transition of macrophage, and alleviate ALI in endotoxemia mice compared with AOzyme group. By addressing the critical factor in the pathogenesis of sepsis‐related ALI through restoring efferocytosis activity, the ACM‐based antioxidant nanozyme in this study is envisioned to provide a promising strategy to treat this complex and challenging disease.