RRC ID 41927
著者 Takano S, Aramaki Y, Tsuchiya S.
タイトル Physicochemical properties of liposomes affecting apoptosis induced by cationic liposomes in macrophages.
ジャーナル Pharm Res
Abstract PURPOSE:Cationic liposomes are expected to be useful as nonviral vectors for gene delivery. Cationic liposomes showed cytotoxicity, and we proposed that the cytotoxicity is through apoptosis. In this study, we examined the effects of liposomal properties, such as liposomal charge, size, membrane fluidity, and PEG coating, on the induction of apoptosis in the macrophage-like cell line RAW264.7.
METHODS:RAW264.7 cells were treated with liposomes, and the induction of apoptosis was evaluated by monitoring the changes in DNA content by flow cytometry. The association of liposomes with cells and the generation of reactive oxygen species (ROS) were also measured by flow cytometry.
RESULTS:The induction of apoptosis of RAW264.7 cells was dependent on the concentrations of stearylamine or cholesterol, a component of cationic liposomes. A significant correlation was observed between the degree of apoptosis and association of cationic liposomes with the cells. Coating the liposomal surface with polyethylene glycol (PEG) decreased the association of cationic liposomes with RAW264.7 cells and reduced the induction of apoptosis. Liposomal size also affected the induction of apoptosis, and larger liposomes showed a higher degree of apoptosis induction. Furthermore, ROS, which were required for the induction of apoptosis by cationic liposomes, were generated in a cholesterol content-dependent manner, and ROS generation was also decreased by PEG coating as the association and the induction of apoptosis were reduced.
CONCLUSIONS:The degree of apoptosis is related to the extent of association of cationic liposomes with cells and is related to the generation of ROS.
巻・号 20(7)
ページ 962-8
公開日 2003-7-1
DOI 10.1023/a:1024441702398
PMID 12880280
MeSH Animals Apoptosis / drug effects* Apoptosis / physiology Cations Chemical Phenomena Chemistry, Physical Liposomes / chemistry* Liposomes / pharmacology* Macrophages / drug effects* Macrophages / physiology Mice Reactive Oxygen Species / metabolism
IF 3.242
引用数 47
WOS 分野 CHEMISTRY, MULTIDISCIPLINARY PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)