Comparison of adriamycin and derivatives uptake into large unilamellar lipid vesicles in response to a membrane potential.
Comparison of adriamycin and derivatives uptake into large unilamellar lipid vesicles in response to a membrane potential.
复制标题
比较阿霉素及其衍生物对膜电位的响应而进入大单层脂质囊泡的情况。
DOI：
10.1016/0005-2736(93)90148-s
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
J. Ruysschaert
中科院分区：
文献类型：
--
作者：
M. Praet;F. Defrise;J. Ruysschaert
The uptake of adriamycin (ADM) and several derivatives into large unilamellar vesicles (LUV) displaying a transmembrane potential and having a lipid composition close to that of the inner mitochondrial membrane has been measured. Drug association to neutral liposomes, made of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) (70:30, w/w) was shown to be potential-dependent: in the absence of potential, accumulation of drug was almost undetectable, whereas between 11 and 50 nmol of drug/αmol phospholipid, depending on the anthracycline used, was associated to LUV exhibiting a membrane potential after 1 h incubation. Association of drugs to LUV with a lipid composition closer to that of the inner mitochondrial (cardiolipin, CL, 20%; PC 50%; PE 30%, w/w) and displaying a membrane potential is higher than with neutral vesicles (between 40 and 76 nmol of anthracycline/αmol phospholipid after 1 h incubation). Since it is known that ADM and derivatives have a high affinity for CL, a fraction of the associated drug may bind to CL on the outer side of the vesicles. This was confirmed by the fact that, in the absence of potential, between 40 and 56 nmol of anthracycline/αmol phospholipid was still associated to LUV containing CL. In order to discriminate between drug absorbed at the surface of the LUV and drug accumulated inside the LUV, an anthracycline fluorescence quencher (I−) was used. It was shown on neutral LUV displaying a membrane potential, that betwen 55 and 81% of the associated drug is actually entrapped inside the vesicles, inaccessible to the quencher. These percentages decreased to between 41 and 68%, respectively, in the presence of LUV containing CL and exhibiting a membrane potential, whereas for LUV of the same composition but displaying no membrane potential almost all the associated drug is absorbed on the outer face of the LUV, accessible to the quencher, and likely bound to CL. This study brings evidence that antitoumour anthracycline despite important structural homologies do not accumulate to the same extent into vesicles mimicking the lipid composition and the membrane potential of mitoplasts. This ability to reach the matrix compartment of mitochondria could partly explain the differences of cardiotoxicities associated to anthracyclines with a closely related molecural structure.
登录
查看更多内容
单层磷脂酰胆碱囊泡的蒽环类药物选择性的结构基础：平衡结合研究。
影响因子：
2.9
作者：
Burke,TG;Tritton,TR
通讯作者：
Tritton,TR
蒽环类药物与单层磷脂酰胆碱囊泡结合的位置和动力学。
影响因子：
2.9
作者：
Burke,TG;Tritton,TR
通讯作者：
Tritton,TR
DOI：
10.1089/cdd.1986.3.251
发表时间：
1986
期刊：
Cancer drug delivery
影响因子：
--
作者：
Theodore J. Lampidis;Awtar Krishan;L. Planas;Haim Tapiero
通讯作者：
Theodore J. Lampidis;Awtar Krishan;L. Planas;Haim Tapiero
DOI：
--
发表时间：
1986-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
K. Davies;J. Doroshow
通讯作者：
K. Davies;J. Doroshow
N-乙酰半胱氨酸抑制阿霉素引发的膜损伤：可能由硫醇依赖性脂质过氧化胞质抑制剂介导。
影响因子：
3.8
作者：
Powell,SR;McCay,PB
通讯作者：
McCay,PB