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.
Highlights
One of the major biomedical applications of carbon nanotubes (CNT) is their use as nanovectors in drug delivery paradigms
We studied the time-course of uptake of NBD-PC-coated single-walled carbon nanotubes (SWCNT), NBD-PS-coated-SWCNT and NBDPS-coated and Annexin V treated SWCNT by RAW264.7 macrophages
Specific interfacing of SWCNT with phagocytic cells of the immune system – macrophages, microglia, and dendritic cells - is important for several reasons
Summary
One of the major biomedical applications of carbon nanotubes (CNT) is their use as nanovectors in drug delivery paradigms. The universal nature of the engulfment of covalently functionalized CNT by different types of cells precludes the possibility of their targeted delivery to specific cells [9]. This stimulated new lines of research on targeted interfacing of single walled carbon nanotubes (SWCNT) with living cells through specific coatings mimicking the cell surface [10]. Glycopolymers - that mimic cell surface mucin glycoproteins and facilitate carbohydrate receptor interactions - have been developed to stimulate targeted engulfment of SWCNT by specific types of cells [10,11]
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