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dc.contributor.authorLanger, Robert
dc.contributor.authorKamaly, Nazila
dc.contributor.authorFredman, Gabrielle
dc.contributor.authorSubramanian, Manikandan
dc.contributor.authorGadde, Suresh
dc.contributor.authorPesic, Alexsandar
dc.contributor.authorCheung, Louis
dc.contributor.authorFayad, Zahi A.
dc.contributor.authorTabas, Ira
dc.contributor.authorCameron Farokhzad, Omid
dc.date.accessioned2013-10-04T12:23:08Z
dc.date.available2013-10-04T12:23:08Z
dc.date.issued2013-03
dc.date.submitted2012-12
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/81300
dc.description.abstractExcessive inflammation and failed resolution of the inflammatory response are underlying components of numerous conditions such as arthritis, cardiovascular disease, and cancer. Hence, therapeutics that dampen inflammation and enhance resolution are of considerable interest. In this study, we demonstrate the proresolving activity of sub–100-nm nanoparticles (NPs) containing the anti-inflammatory peptide Ac2-26, an annexin A1/lipocortin 1-mimetic peptide. These NPs were engineered using biodegradable diblock poly(lactic-co-glycolic acid)-b-polyethyleneglycol and poly(lactic-co-glycolic acid)-b-polyethyleneglycol collagen IV–targeted polymers. Using a self-limited zymosan-induced peritonitis model, we show that the Ac2-26 NPs (100 ng per mouse) were significantly more potent than Ac2-26 native peptide at limiting recruitment of polymononuclear neutrophils (56% vs. 30%) and at decreasing the resolution interval up to 4 h. Moreover, systemic administration of collagen IV targeted Ac2-26 NPs (in as low as 1 µg peptide per mouse) was shown to significantly block tissue damage in hind-limb ischemia-reperfusion injury by up to 30% in comparison with controls. Together, these findings demonstrate that Ac2-26 NPs are proresolving in vivo and raise the prospect of their use in chronic inflammatory diseases such as atherosclerosis.en_US
dc.description.sponsorshipNational Heart, Lung, and Blood Institute (Program of Excellence in Nanotechnology Award Contract HHSN268201000045C)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant CA151884)en_US
dc.description.sponsorshipProstate Cancer Foundation (Award in Nanotherapeutics)en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1303377110en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleDevelopment and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticlesen_US
dc.typeArticleen_US
dc.identifier.citationKamaly, N., G. Fredman, M. Subramanian, S. Gadde, A. Pesic, L. Cheung, Z. A. Fayad, R. Langer, I. Tabas, and O. Cameron Farokhzad. “Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles.” Proceedings of the National Academy of Sciences 110, no. 16 (April 16, 2013): 6506-6511.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.mitauthorLanger, Roberten_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsKamaly, N.; Fredman, G.; Subramanian, M.; Gadde, S.; Pesic, A.; Cheung, L.; Fayad, Z. A.; Langer, R.; Tabas, I.; Cameron Farokhzad, O.en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-4255-0492
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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