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

Konduru, NV and Tyurina, YY and Feng, W and Basova, LV and Belikova, NA and Bayir, H and Clark, K and Rubin, M and Stolz, D and Vallhov, H and Scheynius, A and Witasp, E and Fadeel, B and Kichambare, PD and Star, A and Kisin, ER and Murray, AR and Shvedova, AA and Kagan, VE (2009) Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo. PLoS ONE, 4 (2).

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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.

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Creators	Email	Pitt Username	ORCID
Konduru, NV
Tyurina, YY	yyt1@pitt.edu	YYT1
Feng, W
Basova, LV
Belikova, NA
Bayir, H	hub22@pitt.edu	HUB22	0000-0003-2361-4120
Clark, K	kac220@pitt.edu	KAC220
Rubin, M
Stolz, D	donna.stolz@pitt.edu	DSTOLZ
Vallhov, H
Scheynius, A
Witasp, E
Fadeel, B
Kichambare, PD
Star, A	astar@pitt.edu	ASTAR
Kisin, ER
Murray, AR
Shvedova, AA
Kagan, VE	kagan@pitt.edu	KAGAN