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However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for epidermal growth factor receptor and C\u2500C chemokine receptor type 2 is explored in lung tumors. The addition of active targeting ligands on MSNs enhances their uptake in vitro but fails to promote specific delivery to tumors in vivo, when administered systemically via the blood or locally to the lung into immunocompetent murine lung cancer models. Ineffective tumor targeting is due to efficient clearance of the MSNs by the phagocytic cells of the liver, spleen, and lung. These limitations, however, are successfully overcome using a novel organ\u2010restricted vascular delivery (ORVD) approach. ORVD in isolated and perfused mouse lungs of\n                    <jats:italic>Kras<\/jats:italic>\n                    \u2010mutant mice enables effective nanoparticle extravasation from the tumor vasculature into the core of solid lung tumors. In this study, ORVD promotes tumor cell\u2010specific uptake of nanoparticles at cellular resolution independent of their functionalization with targeting ligands. Organ\u2010restricted vascular delivery thus opens new avenues for optimized nanoparticles for lung cancer therapy and may have broad applications for other vascularized tumor types.\n                  <\/jats:p>","DOI":"10.1002\/adtp.202000017","type":"journal-article","created":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T18:58:16Z","timestamp":1589396296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Organ\u2010Restricted Vascular Delivery of Nanoparticles for Lung Cancer Therapy"],"prefix":"10.1002","volume":"3","author":[{"given":"Deniz A.","family":"B\u00f6l\u00fckbas","sequence":"first","affiliation":[{"name":"Comprehensive Pneumology Center (CPC) University Hospital Ludwig\u2010Maximilians University and Helmholtz Zentrum M\u00fcnchen, Munich, Germany. Member of the German Center for Lung Research (DZL)  Munich 81377 Germany"},{"name":"Lung Bioengineering and Regeneration Department of Experimental Medical Sciences, Stem Cell Centre Wallenberg Center for Molecular Medicine Lund University Cancer Centre (LUCC) Lund University  Lund 22362 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Datz","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for NanoScience (CeNS) University of Munich (LMU)  Munich 81377 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Meyer\u2010Schwickerath","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Center (CPC) University Hospital Ludwig\u2010Maximilians University and Helmholtz Zentrum M\u00fcnchen, Munich, Germany. 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Member of the German Center for Lung Research (DZL)  Munich 81377 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothee","family":"G\u00f6\u00dfl","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for NanoScience (CeNS) University of Munich (LMU)  Munich 81377 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malamati","family":"Vreka","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Center (CPC) University Hospital Ludwig\u2010Maximilians University and Helmholtz Zentrum M\u00fcnchen, Munich, Germany. Member of the German Center for Lung Research (DZL)  Munich 81377 Germany"},{"name":"Laboratory for Molecular Respiratory Carcinogenesis Department of Physiology Faculty of Medicine University of Patras  Patras 26504 Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Center (CPC) University Hospital Ludwig\u2010Maximilians University and Helmholtz Zentrum M\u00fcnchen, Munich, Germany. Member of the German Center for Lung Research (DZL)  Munich 81377 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Argyo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for NanoScience (CeNS) University of Munich (LMU)  Munich 81377 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine H.","family":"van Rijt","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Center (CPC) University Hospital Ludwig\u2010Maximilians University and Helmholtz Zentrum M\u00fcnchen, Munich, Germany. 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