Targeted delivery of phosphatidylserinecoated single walled carbon nanotubes to macrophages.
Kagan VE; Tyurina YY; Konduru N; Basova LV; Stolz D; Kisin ER; Murray AR; Fadeel B; Shvedova AA
Toxicologist 2007 Mar; 96(1):233
Non-functionalized single walled carbon nanotubes (SWCNT) are not effectively taken-up by phagocytes. In contrast, apoptotic cells with externalized phosphatidylserine (PS) and non-apoptotic cells enriched with PS on their surface are well recognized by macrophages resulting in the suppression of their ROS and RNS production. We hypothesized that coating of SWCNT with PS could interface them with macrophages and stimulate their recognition and engulfment. SEM imaging revealed engulfment of PS-SWCNT by RAW264.7 macrophages and protrusions of SWCNT fibers through the surface into the interior of macrophages. Noncoated and PC-SWCNT were less attractive targets for the macrophages. TEM evaluations of the uptake of SWCNT showed that RAW264.7 macrophages expeditiously phagocytosed PS-SWCNT while less pronounced engulfment of PCSWCNT and non-coated SWCNT was detected. In addition, macrophages co-incubated with PS-SWCNT had more endocytotic vesicles with entrapped SWCNT compared to macrophages exposed to PC-SWCNT or non-coated SWCNT. PSSWCNT pretreated with Annexin V were phagocytosed at a much lower frequency. PS-SWCNT (but no PC-SWCNT) effectively suppressed LPS-induced production of TNF-á by macrophages. Interestingly, in vivo, PS-SWCNTS caused a more robust inflammatory response as compared with PC-SWCNT or non-coated SWCNT. This was documented by a greater total number of cells and PMNs as well as by increased production of TNF-á. PS-SWCNT were preferably phagocytosed by macrophages obtained from BAL as compared to PC-SWCNT or noncoated SWCNT.
Cell-alteration; Cell-damage; Cellular-reactions; Cell-biology; Cell-function; Cell-metabolism; Cell-morphology; Cell-transformation; Chemical-analysis; Chemical-composition; Fibrous-bodies; In-vivo-studies; Nanotechnology
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina
University of Pittsburgh at Pittsburgh