Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo

• Published in: PloS one 2009-02, Vol.4 (2), p.e4398
• Main Authors: Konduru, Nagarjun V, Tyurina, Yulia Y, Feng, Weihong, Basova, Liana V, Belikova, Natalia A, Bayir, Hülya, Clark, Katherine, Rubin, Marc, Stolz, Donna, Vallhov, Helen, Scheynius, Annika, Witasp, Erika, Fadeel, Bengt, Kichambare, Padmakar D, Star, Alexander, Kisin, Elena R, Murray, Ashley R, Shvedova, Anna A, Kagan, Valerian E
• Format: Article
• Language: English
• Subjects: Alveoli; Animals; Annexin V; Antioxidants; Apoptosis; Biology; Biotechnology; Biotechnology/Chemical Biology of the Cell; Brain; Carbon; Cell Line, Tumor; Coating; Cytochrome; Cytochrome c; Cytokines; Dendritic cells; Endocytosis; Environmental health; Female; Flow Cytometry; Free radicals; Gangrene; Health aspects; HeLa Cells; Humans; Immunology/Antigen Processing and Recognition; Immunology/Immune Response; In Vitro Techniques; Inflammation; Laboratories; Listeria; Listeria monocytogenes; Lungs; Macrophages; Macrophages - metabolism; Medicin och hälsovetenskap; Medicine; Mice; Mice, Inbred C57BL; Microglia; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Monocytes; Nanoparticles; Nanotechnology; Nanotubes; Nanotubes, Carbon - chemistry; Nanotubes, Carbon - toxicity; Occupational health; Occupational safety; Pathology; Phagocytes; Phagocytes - metabolism; Phosphatidylserine; Phosphatidylserines - chemistry; Phosphatidylserines - metabolism; Phospholipids; Physiology; Protein binding; Public health; Rats; Rheumatoid arthritis; Rodents; Scholarships & fellowships; Single wall carbon nanotubes; Toxicology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004398

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.