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dc.contributor.authorWibroe, Peter Popp
dc.contributor.authorAnselmo, Aaron C
dc.contributor.authorNilsson, Per
dc.contributor.authorSarode, Apoorva
dc.contributor.authorGupta, Vivek
dc.contributor.authorUrbanics, Rudolf
dc.contributor.authorSzebeni, Janos
dc.contributor.authorHunter, Alan Christy
dc.contributor.authorMitragotri, Samir
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorMoghimi, Seyed Moein
dc.date.accessioned2018-04-04T08:12:00Z
dc.date.available2018-04-04T08:12:00Z
dc.date.created2017-08-02T14:40:58Z
dc.date.issued2017
dc.identifier.citationNature Nanotechnology. 2017, 12 (6), 589-594.nb_NO
dc.identifier.issn1748-3387
dc.identifier.urihttp://hdl.handle.net/11250/2492500
dc.description.abstractIntravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust pulmonary intravascular macrophage clearance of nanoparticles in mediating adverse cardiopulmonary distress in pigs irrespective of complement activation. Specifically, we show that delaying particle recognition by macrophages within the first few minutes of injection overcomes adverse reactions in pigs using two independent approaches. First, we changed the particle geometry from a spherical shape (which triggers cardiopulmonary distress) to either rod- or disk-shape morphology. Second, we physically adhered spheres to the surface of erythrocytes. These strategies, which are distinct from commonly leveraged stealth engineering approaches such as nanoparticle surface functionalization with poly(ethylene glycol) and/or immunological modulators, prevent robust macrophage recognition, resulting in the reduction or mitigation of adverse cardiopulmonary distress associated with nanopharmaceutical administration.nb_NO
dc.language.isoengnb_NO
dc.publisherNature Publishing Groupnb_NO
dc.titleBypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytesnb_NO
dc.typeJournal articlenb_NO
dc.description.versionsubmittedVersionnb_NO
dc.source.pagenumber589-594nb_NO
dc.source.volume12nb_NO
dc.source.journalNature Nanotechnologynb_NO
dc.source.issue6nb_NO
dc.identifier.doi10.1038/nnano.2017.47
dc.identifier.cristin1483873
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.description.localcodeThis is a submitted manuscript of an article published by Nature Publishing Group in Nature Nanotechnology, 0 April 2017nb_NO
cristin.unitcode194,65,15,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.ispublishedtrue
cristin.fulltextpreprint
cristin.qualitycode2


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