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Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of ALI\/ARDS and represent a promising therapeutic target. However, the clinical application of deoxyribonuclease I (DNase I), the only drug currently available to clear NETs, is limited due to the lack of precise and efficient delivery strategies. Therefore, targeted delivery of DNase I to the inflamed lung remains a critical issue to be addressed. Herein, a novel biomimetic DNase I delivery system is developed (DCNV) that employs genetically and bioorthogonally engineered cellular nanovesicles for pulmonary NETs clearance. The CXC motif chemokine receptor 2 overexpressed cellular nanovesicles can mimic the inflammatory chemotaxis of neutrophils in ALI\/ARDS, leading to enhanced lung accumulation. Furthermore, DNase I immobilized through bioorthogonal chemistry exhibits remarkable enzymatic activity in NETs degradation, thus restraining inflammation and safeguarding lung tissue in the lipopolysaccharide\u2010induced ALI murine model. Collectively, the findings present a groundbreaking proof\u2010of\u2010concept in the utilization of biomimetic cellular nanovesicles to deliver DNase I for treating ALI\/ARDS. This innovative strategy may usher in a new era in the development of pharmacological interventions for various inflammation\u2010related diseases.<\/jats:p>","DOI":"10.1002\/advs.202303053","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:31:34Z","timestamp":1695861094000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Genetically Engineered Cellular Nanovesicle as Targeted DNase I Delivery System for the Clearance of Neutrophil Extracellular Traps in Acute Lung Injury"],"prefix":"10.1002","volume":"10","author":[{"given":"Yang","family":"Du","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang 310009 China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province  Hangzhou 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