Lysosomal membrane destabilization induced by high accumulation of single-walled carbon nanohorns in murine macrophage RAW 264.7.
Cellular responses to graphene-based, nanometer-sized materials, such as carbon nanotubes and single-walled carbon nanohorns (SWNHs), have previously been studied at low-uptake levels. Here, by exploiting the availability of large quantities of SWNHs, cytotoxicity and the immunological responses induced by the abundant uptake of these structures were studied in RAW 264.7 murine macrophages. As much as half the cell interior was pigmented black by SWNHs, which were preferentially localized to lysosomes. High-uptake was shown to destabilize lysosomal membranes and generate reactive oxygen species that resulted in apoptotic, as well as necrotic, cell death. Despite these dramatic responses, only low levels of cytokines were released. The results will be interesting for future studies of the nanocarbon toxicity mechanisms and for medical applications of nanocarbons, especially those relying on lysosomes as target organelles for drug delivery or imaging.
National Institute of Advanced Industrial Science and Technology, Nanotube Research Center, 5-2, 1-1-1 Higashi, Tsukuba 305-8565, Japan.
Yoshio
Y
Tahara
Maki
M
Nakamura
Mei
M
Yang
Minfang
M
Zhang
Sumio
S
Iijima
Masako
M
Yudasaka
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004705:Endocytosis; D018836:Inflammation Mediators / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species