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首页> 外文期刊>Anti-Cancer Drug Design >Cancerostatic octadecylpiperidinoylphosphate liposomes: effect of composition on uptake by and toxicity to J774 mouse macrophage cells and MT1 breast cancer cells in vitro.
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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.

机译：抗癌的十八烷基哌啶子基磷酸酯脂质体：该组合物对体外J774小鼠巨噬细胞和MT1乳腺癌细胞摄取和毒性的影响。

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摘要

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 microM. 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 approximately 1.
机译：研究了由抗癌的十八烷基-（N，N-二甲基哌啶子基-4-基）-磷酸酯（OPP）制备的脂质体，以表征组合物对细胞毒性的影响并最大程度地降低对免疫系统的副作用。在电荷，胆固醇含量和空间稳定性方面使用了不同组成的脂质体。分别采用荧光测量和MTT测定研究摄取和细胞毒性对体外J774小鼠巨噬细胞和MT1人乳腺癌细胞的影响。由于它们的内吞能力，与肿瘤细胞相比，巨噬细胞的摄取通常更高。带负电荷，胆固醇少且空间稳定的OPP脂质体显示两种细胞系的总摄取量和内部摄取量最低。另一方面，对于所研究的两种细胞系，这些脂质体也是最具细胞毒性的脂质体，其抑制浓度在50至80 microM之间。细胞毒性与细胞摄取无关，很可能是由其他机制引起的。结果表明，抗癌脂质体对巨噬细胞具有依赖成分的毒性作用，必须认真考虑。为了进行体内实验，脂质体应带负电荷并在空间上稳定，并由OPP和胆固醇组成，摩尔比约为1。

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