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Lipid nanoparticles and polymersomes can direct the organ\u2010selective delivery of mRNAs or gene editing machineries, but their delivery is limited to mostly liver, spleen, and lung. A platform that enables delivery to these and other target organs is urgently needed. Here, a library of glycocalyx\u2010mimicking nanoparticles (GlyNPs) comprising five randomly combined sugar moieties is generated, and direct in vivo library screening is used to identify GlyNPs with preferential biodistribution in liver, spleen, lung, kidneys, heart, and brain. Each organ\u2010targeting GlyNP hit show cellular tropism within the organ. Liver, kidney, and spleen\u2010targeting GlyNP hits equipped with therapeutics effectively can alleviate the symptoms of acetaminophen\u2010induced liver injury, cisplatin\u2010induced kidney injury, and immune thrombocytopenia in mice, respectively. Furthermore, the differential organ targeting of GlyNP hits is influenced not by the protein corona but by the sugar moieties displayed on their surface. It is envisioned that the GlyNP\u2010based platform may enable the organ\u2010 and cell\u2010targeted delivery of therapeutic cargoes.<\/jats:p>","DOI":"10.1002\/adma.202311283","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T02:34:45Z","timestamp":1710556485000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Glycocalyx\u2010Mimicking Nanoparticles with Differential Organ Selectivity for Drug Delivery and Therapy"],"prefix":"10.1002","volume":"36","author":[{"given":"Dohyeon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biological Sciences KAIST Institute of BioCentury Korea Advanced Institute of Science and Technology (KAIST)  291 Daehak\u2010ro Daejeon 34141 Republic of Korea"},{"name":"Center for Precision Bio\u2010Nanomedicine KAIST  291 Daehak\u2010ro Daejeon 34141 Republic of 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