Nature nanotechnology · 2021
Supramolecular arrangement of protein in nanoparticle structures predicts nanoparticle tropism for neutrophils in acute lung inflammation.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод в очереди
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Myerson Jacob W, Patel Priyal N, Rubey Kathryn M, Zamora Marco E, Zaleski Michael H, Habibi Nahal, Walsh Landis R, Lee Yi-Wei, Luther David C, Ferguson Laura T, Marcos-Contreras Oscar A, Glassman Patrick M, Mazaleuskaya Liudmila L, Johnston Ian, Hood Elizabeth D, Shuvaeva Tea, Wu Jichuan, Zhang Hong-Ying, Gregory Jason V, Kiseleva Raisa Y, Nong Jia, Grosser Tilo, Greineder Colin F, Mitragotri Samir, Worthen George S, Rotello Vincent M, Lahann Joerg, Muzykantov Vladimir R, Brenner Jacob S
Аннотация
This study shows that the supramolecular arrangement of proteins in nanoparticle structures predicts nanoparticle accumulation in neutrophils in acute lung inflammation (ALI). We observed homing to inflamed lungs for a variety of nanoparticles with agglutinated protein (NAPs), defined by arrangement of protein in or on the nanoparticles via hydrophobic interactions, crosslinking and electrostatic interactions. Nanoparticles with symmetric protein arrangement (for example, viral capsids) had no selectivity for inflamed lungs. Flow cytometry and immunohistochemistry showed NAPs have tropism for pulmonary neutrophils. Protein-conjugated liposomes were engineered to recapitulate NAP tropism for pulmonary neutrophils. NAP uptake in neutrophils was shown to depend on complement opsonization. We demonstrate diagnostic imaging of ALI with NAPs; show NAP tropism for inflamed human donor lungs; and show that NAPs can remediate pulmonary oedema in ALI. This work demonstrates that structure-dependent tropism for neutrophils drives NAPs to inflamed lungs and shows NAPs can detect and treat ALI.
Предметные рубрики MeSH
Acute DiseaseAgglutinationAnimalsAntibodiesCross-Linking ReagentsDextransHumansInflammationLipopolysaccharidesLiposomesLungMaleMice, Inbred C57BLMuramidaseNanoparticlesNeutrophilsOpsonin ProteinsProteinsStatic ElectricityTissue DistributionTomography, Emission-Computed, Single-PhotonTomography, X-Ray ComputedMice