title: Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo.
abstract: Broad applications of single-walled carbon nanotubes (SWCNT) dictate the necessity to better understand their health effects. Poor recognition of non-functionalized SWCNT by phagocytes is prohibitive towards controlling their biological action. We report that SWCNT coating with a phospholipid "eat-me" signal, phosphatidylserine (PS), makes them recognizable in vitro by different phagocytic cells - murine RAW264.7 macrophages, primary monocyte-derived human macrophages, dendritic cells, and rat brain microglia. Macrophage uptake of PS-coated nanotubes was suppressed by the PS-binding protein, Annexin V, and endocytosis inhibitors, and changed the pattern of pro- and anti-inflammatory cytokine secretion. Loading of PS-coated SWCNT with pro-apoptotic cargo (cytochrome c) allowed for the targeted killing of RAW264.7 macrophages. In vivo aspiration of PS-coated SWCNT stimulated their uptake by lung alveolar macrophages in mice. Thus, PS-coating can be utilized for targeted delivery of SWCNT with specified cargoes into professional phagocytes, hence for therapeutic regulation of specific populations of immune-competent cells.
authors.affiliation: Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Nagarjun V
authors.initials: NV
authors.lastname: Konduru
authors.forename: Yulia Y
authors.initials: YY
authors.lastname: Tyurina
authors.forename: Weihong
authors.initials: W
authors.lastname: Feng
authors.forename: Liana V
authors.initials: LV
authors.lastname: Basova
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Belikova
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayir
authors.forename: Katherine
authors.initials: K
authors.lastname: Clark
authors.forename: Marc
authors.initials: M
authors.lastname: Rubin
authors.forename: Donna
authors.initials: D
authors.lastname: Stolz
authors.forename: Helen
authors.initials: H
authors.lastname: Vallhov
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Erika
authors.initials: E
authors.lastname: Witasp
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
authors.forename: Padmakar D
authors.initials: PD
authors.lastname: Kichambare
authors.forename: Alexander
authors.initials: A
authors.lastname: Star
authors.forename: Elena R
authors.initials: ER
authors.lastname: Kisin
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Murray
authors.forename: Anna A
authors.initials: AA
authors.lastname: Shvedova
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000633:toxicity; D010586:Phagocytes / Q000378:metabolism*; D010718:Phosphatidylserines / Q000737:chemistry* / Q000378:metabolism; D051381:Rats
chemical_list: D037742:Nanotubes, Carbon; D010718:Phosphatidylserines