Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes

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dc.cclicenceCC-BY-NCen
dc.contributor.authorWibroe, Peter P.en
dc.contributor.authorAnselmo, Aaron C.en
dc.contributor.authorNilsson, Per H.en
dc.contributor.authorGupta, Viveken
dc.contributor.authorUrbanics, Rudolfen
dc.contributor.authorSzebeni, Janosen
dc.contributor.authorHunter, Alan Christyen
dc.contributor.authorMitragotri, Samiren
dc.contributor.authorMollnes, Tom Eiriken
dc.contributor.authorMoghimi, S. M.en
dc.date.acceptance2017-02-27en
dc.date.accessioned2017-07-25T09:22:31Z
dc.date.available2017-07-25T09:22:31Z
dc.date.issued2017-05-03
dc.descriptionThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.en
dc.description.abstractIntravenously injected nanopharmaceuticals induce adverse cardiopulmonary reactions in sensitive human subjects and these reactions are reproducible in pigs. The underlying mechanisms are poorly understood, but a role for both the complement system and reactive macrophages has been implicated. Here we show the dominance and importance of early pulmonary intravascular macrophage clearance kinetics in adverse particle-mediated cardiopulmonary distress in pigs and irrespective of complement activation. Delaying particle recognition by macrophages within the first few minutes of injection overcome adverse reactions in pigs. This was achieved by two independent approaches: (i) changing particle geometry from a spherical shape (which trigger cardiopulmonary distress) to either rod- or disk-shape morphology and (ii) by physically adhering spheres to the surface of erythrocytes. These approaches bypasses particle surface engineering approaches to prevent robust macrophage recognition as well as the use of immunological or pharmacological modulators to reduce/overcome nanomedicine related adverse cardiopulmonary distress.en
dc.funderDanish Agency for Science, Technology and Innovation (Det Strategiske Forskningsrad (09-065746)en
dc.funderEuropean Community (602699)en
dc.funderNational Institute of Health (R01HL129179)en
dc.identifier.citationWibroe, P.P. et al. (2017) Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes. Nature nanotechnology, 12 (6), pp. 589-596en
dc.identifier.doihttps://doi.org/10.1038/nnano.2017.47
dc.identifier.issn1748-3387
dc.identifier.urihttp://hdl.handle.net/2086/14328
dc.language.isoenen
dc.peerreviewedNoen
dc.projectid09-065746en
dc.projectid602699en
dc.projectidR01HL129179en
dc.publisherNatureen
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.subjectPulmonary Intravascular Macrophagesen
dc.subjectInduced Complement Activationen
dc.subjectAcute Lung Injuryen
dc.subjectLiposomalDoxorubicinen
dc.subjectClinical Oncologyen
dc.subjectIn Vitro Phase 1 Modelen
dc.subjectPhagocytosisen
dc.subjectParticlesen
dc.titleBypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytesen
dc.typeArticleen

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