Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo.
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.
Konduru
Nagarjun V
NV
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.
Tyurina
Yulia Y
YY
Feng
Weihong
W
Basova
Liana V
LV
Belikova
Natalia A
NA
Bayir
Hülya
H
Clark
Katherine
K
Rubin
Marc
M
Stolz
Donna
D
Vallhov
Helen
H
Scheynius
Annika
A
Witasp
Erika
E
Fadeel
Bengt
B
Kichambare
Padmakar D
PD
Star
Alexander
A
Kisin
Elena R
ER
Murray
Ashley R
AR
Shvedova
Anna A
AA
Kagan
Valerian E
VE
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
D037742:Nanotubes, Carbon; D010718:Phosphatidylserines