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As the burgeoning nanotherapeutic, the right\u2010side\u2010out orientation self\u2010assembly and pathological dependent \u201con\u2010demand\u201d cargo release of cell membrane camouflaged nanocarriers remarkably limit further development for practical applications. In the present study, a spontaneously right\u2010side\u2010out\u2010orientated coupling\u2010driven ROS\u2010sensitive nanotherapeutic has been constructed for target endothelial cells (ECs) repair through the synergistic effects of spontaneously right\u2010side\u2010out\u2010orientated camouflaging. This condition results from the specific affinity between the intracellular domain of key transmembrane receptors band 3 on cell membrane inner leaflet and the corresponding P4.2 peptide\u2010modified nanoparticles without the additional coextrusion. The \u201con\u2010demand\u201d cargo release results from the pathological ROS\u2010cleavable prodrug. Particularly, the red blood cell camouflaged nanotherapeutics (RBC\u2010LVTNPs) can enhance target drug delivery through low oscillatory shear stress (LSS) blood flow in the injured ECs lesion. Both in vitro and in vivo results collectively confirm that RBC\u2010LVTNPs can restore the damaged ECs and function with the recovered vascular permeability and low inflammation microenvironment. The findings provide a powerful and universal approach for developing the biomimetic cell membrane camouflaged nanotechnology.<\/jats:p>","DOI":"10.1002\/advs.202205093","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T01:00:55Z","timestamp":1674781255000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Spontaneously Right\u2010Side\u2010Out\u2010Orientated Coupling\u2010Driven ROS\u2010Sensitive Nanoparticles on Cell Membrane Inner Leaflet for Efficient Renovation in Vascular Endothelial Injury"],"prefix":"10.1002","volume":"10","author":[{"given":"Xian","family":"Qin","sequence":"first","affiliation":[{"name":"Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular Implants Bioengineering College of Chongqing University  Chongqing 400030 China"},{"name":"Chongqing Municipality Clinical 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