Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis

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dc.contributor.authorKamaly, Nazila
dc.contributor.authorFredman, Gabrielle
dc.contributor.authorFojas, Jhalique Jane R.
dc.contributor.authorSubramanian, Manikandan
dc.contributor.authorChoi, Won Iia
dc.contributor.authorZepeda, Katherinea
dc.contributor.authorVilos, Cristiana
dc.contributor.authorYu, Mikyunga
dc.contributor.authorGadde, Suresha
dc.contributor.authorWu, Juna
dc.contributor.authorMilton, Jaclyna
dc.contributor.authorCarvalho, Leitao
dc.contributor.authorFernandes, Livia
dc.contributor.authorHasan, Moaraja
dc.contributor.authorGao, Huayia
dc.contributor.authorNguyen, Vance
dc.contributor.authorHarris, Jordana
dc.contributor.authorTabas, Ira
dc.contributor.authorFarokhzad, Omid C.
dc.date.accessioned2022-07-26T15:04:35Z
dc.date.available2022-07-26T15:04:35Z
dc.date.issued2016-05
dc.descriptionIndexación: Scopuses
dc.description.abstractInflammation is an essential protective biological response involving a coordinated cascade of signals between cytokines and immune signaling molecules that facilitate return to tissue homeostasis after acute injury or infection. However, inflammation is not effectively resolved in chronic inflammatory diseases such as atherosclerosis and can lead to tissue damage and exacerbation of the underlying condition. Therapeutics that dampen inflammation and enhance resolution are currently of considerable interest, in particular those that temper inflammation with minimal host collateral damage. Here we present the development and efficacy investigations of controlled-release polymeric nanoparticles incorporating the anti-inflammatory cytokine interleukin 10 (IL-10) for targeted delivery to atherosclerotic plaques. Nanoparticles were nanoengineered via self-assembly of biodegradable polyester polymers by nanoprecipitation using a rapid micromixer chip capable of producing nanoparticles with retained IL-10 bioactivity post-exposure to organic solvent. A systematic combinatorial approach was taken to screen nanoparticles, resulting in an optimal bioactive formulation from in vitro and ex vivo studies. The most potent nanoparticle termed Col-IV IL-10 NP22 significantly tempered acute inflammation in a self-limited peritonitis model and was shown to be more potent than native IL-10. Furthermore, the Col-IV IL-10 nanoparticles prevented vulnerable plaque formation by increasing fibrous cap thickness and decreasing necrotic cores in advanced lesions of high fat-fed LDLr-/- mice. These results demonstrate the efficacy and pro-resolving potential of this engineered nanoparticle for controlled delivery of the potent IL-10 cytokine for the treatment of atherosclerosis. © 2016 American Chemical Society.es
dc.description.urihttps://pubs-acs-org.recursosbiblioteca.unab.cl/doi/pdf/10.1021/acsnano.6b01114
dc.identifier.citationIndexación: Scopuses
dc.identifier.doi10.1021/acsnano.6b01114
dc.identifier.issn1936-0851
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/23333
dc.language.isoenes
dc.publisherAmerican Chemical Societyes
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectatherosclerosises
dc.subjectIL-10es
dc.subjectinflammationes
dc.subjectmicrofluidicses
dc.subjectnanomedicinees
dc.subjectpolymeric nanoparticleses
dc.titleTargeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosises
dc.typeArtículoes
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ACS Nano Volume 10, Issue 5, Pages 5280 - 529224 May 2016
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