Interaction of liposomes with cultured cells: possible involvement of lipid peroxidation in cell growth inhibition.
Systematic analyses of the interaction between liposomes and cells were examined. Liposomes were found to affect the growth of mouse NIH 3T3 cells depending upon their size, net charge, and cholesterol content. Among the charged compounds, stearylamine was the most inhibitory and showed complete inhibition of cell growth at 100 microM. The cholesterol-rich and small unilamellar vesicles were more suppressive compared to the cholesterol-poor and multilamellar ones, respectively. The binding assay of liposomes to the cells showed a positive correlation between liposome binding and the extent of growth inhibition. Suppression of liposome uptake by inhibitors of the cytoskeletal system and energy metabolism were suggestive of an endocytotic mechanism for the cellular uptake of liposomes. The growth inhibitory effect seemed secondary to the intracellular uptake of liposomes, and peroxidation of incorporated lipids would lead to cellular damage. Therefore, it is highly recommended that potential growth inhibitory effects associated with the particular composition and other properties of liposomes should be carefully assessed in any human studies, especially for long-term use.
Yoshioka
S
S
Department of Hospital Pharmacy, Gifu University Hospital, Japan.
Okano
Y
Y
Mizukami
Y
Y
Nozawa
Y
Y
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000378:metabolism / Q000494:pharmacology; D006131:Growth Inhibitors; D015227:Lipid Peroxidation / Q000502:physiology*; D008081:Liposomes / Q000378:metabolism / Q000494:pharmacology*
D004337:Drug Carriers; D006131:Growth Inhibitors; D008081:Liposomes