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.

Folate and iron difunctionalized multiwall carbon nanotubes as dual-targeted drug nanocarrier to cancer cells

“…Much research has been carried out, such as the 0008-6223/$ -see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.carbon.2011.01.003 targeted delivery of cisplatin into Ntera-2 cells by FA-modified SWCNTs [20], cytochrome C into phagocytic cells by phosphatidylserine-modified SWCNTs [21], gemcitabine into lymph nodes by NPs-modified multiwall carbon nanotube (MWCNT) [22], doxorubicin (Dox) into WiDr cells by antibody-modified SWCNTs [23] and other related researches [24][25][26][27].…”

Biomolecular coronas provide the biological identity of nanosized materials

“…For example, the lipid component, especially relevant for inhalation scenarios, also plays a crucial role for biorecognition 56 ; thus carbon nanotubes covered by a phospholipid uptake signal, phosphatidylserine, are recognised and cleared by macrophages both in vitro and following inhalation in vivo 57 .…”

Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes

“…6 Other recent work described the enzymatic degradation of functionalized SWCNT in vitro and in vivo, offering the potential for metabolic decomposition of CNT drug constructs. [40][41][42][43] Further, toxicity studies have confirmed the safe in vivo use of functionalized SWCNT. [44][45][46][47] Taken together, these data on renal elimination, enzymatic degradation, and lack of toxicity support continued investigation of SWCNT as a platform in drug development.…”