Inhaled Pro‐Efferocytic Nanozymes Promote Resolution of Acute Lung Injury

Abstract

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.

Engineered Biomimetic Nanovesicles Based on Neutrophils for Hierarchical Targeting Therapy of Acute Respiratory Distress Syndrome

“…In order to study the effect of DHA@ANeu-DDAB on improving the efferocytosis of inflammatory macrophages, CLSM and FCM were used to detect the uptake behavior of apoptotic neutrophils by inflammatory RAW 264.7 macrophages, according to the above experimental scheme (Figure A). Jurkat T cells were selected as the apoptosis model cells, which were commonly used in efferocytosis experiments . First, the apoptosis efficiency of Jurkat T cells induced by UV irradiation for different time periods was investigated.…”

Development of nanozymes for promising alleviation of COVID-19-associated arthritis

“…114 Ji et al created acute lung injury (ALI) mice with serious cytokine storms and lung edema. 115 They observed significant increases of TNF-α, IL-6, and IL-1β in both serum and bronchoalveolar lavage fluid (BALF) (Fig. 3A).…”

Nanozyme-Based Remodeling of Disease Microenvironments for Disease Prevention and Treatment: A Review

“…123,124 Previous studies have shown the presence of certain molecules on the surface of apoptosis cell membranes (ACM) that can attract macrophages and promote their phagocytosis. 125 Ji et al 123 designed an ACM-coated antioxidant nanozyme (AOzyme). The prepared AOzyme could promote the phagocytosis of macrophages, induce macrophage polarization, and exert antiinflammatory effects.…”

“…The bilayer phospholipid membrane structure of cell membranes (CM) can wrap and camouflage the nanozymes and enhance their biocompatibility, whereas the different cell membranes on which they are based can provide them with specific targeting. , Previous studies have shown the presence of certain molecules on the surface of apoptosis cell membranes (ACM) that can attract macrophages and promote their phagocytosis . Ji et al designed an ACM-coated antioxidant nanozyme (AOzyme). The prepared AOzyme could promote the phagocytosis of macrophages, induce macrophage polarization, and exert anti-inflammatory effects.…”