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Cancerostatic octadecylpiperidinoylphosphate liposomes: effect of composition on uptake by and toxicity to J774 mouse macrophage cells and MT1 breast cancer cells in vitro

Item Type:Article
Title:Cancerostatic octadecylpiperidinoylphosphate liposomes: effect of composition on uptake by and toxicity to J774 mouse macrophage cells and MT1 breast cancer cells in vitro
Creators Name:Zeisig, R., Stahn, R., Teppke, A.D. and Arndt, D.
Abstract:Liposomes prepared from the cancerostatic octadecyl-(N,N-dimethylpiperidino-4-yl)-phosphate (OPP) were investigated in order to characterize the influence of composition on cytotoxicity and to minimize side effects on the immune system. Differently composed liposomes with respect to charge, cholesterol content and steric stabilization were used. Fluorescence measurements and the MTT assay were applied to investigate the effect of uptake and cytotoxicity, respectively, on J774 mouse macrophages and MT1 human breast cancer cells in vitro. Because of their endocytotic capability, uptake was generally higher for macrophages compared with tumour cells. OPP liposomes, which are negatively charged, cholesterol-poor and sterically stabilized, showed the lowest total and internal uptake by both cell lines. On the other hand, these liposomes were also the most cytotoxic ones for both cell lines investigated, with an inhibitory concentration of between 50 and 80 μM. Cytotoxicity does not correlate with cellular uptake and is most likely caused by other mechanisms. The results demonstrate that cancerostatic liposomes have composition-dependent toxic effects on macrophages which have to be seriously considered. For therapeutic experiments in vivo liposomes should be negatively charged and sterically stabilized and composed of OPP and cholesterol in a molar ratio of ∼1.
Keywords:Alkylphospholipid, Breast Cancer, Cytotoxicity, Liposome, Macrophage, Animals, Mice
Source:Anti-Cancer Drug Design
ISSN:0266-9536
Publisher:Oxford Univ Press
Volume:16
Number:1
Page Range:19-26
Date:1 January 2001
PubMed:View item in PubMed

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