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顺铂及其阳离子类似物对模型脂质双层相行为和通透性的影响。

Effect of Cisplatin and Its Cationic Analogues in the Phase Behavior and Permeability of Model Lipid Bilayers.

机构信息

Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003Lisboa, Portugal.

iBB─Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1649-003Lisboa, Portugal.

出版信息

Mol Pharm. 2023 Feb 6;20(2):918-928. doi: 10.1021/acs.molpharmaceut.2c00321. Epub 2023 Jan 26.


DOI:10.1021/acs.molpharmaceut.2c00321
PMID:36700695
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9906771/
Abstract

Increasing evidence suggests a critical role of lipids in both the mechanisms of toxicity and resistance of cells to platinum(II) complexes. In particular, cisplatin and other analogues were reported to interact with lipids and transiently promote lipid phase changes both in the bulk membranes and in specific membrane domains. However, these processes are complex and not fully understood. In this work, cisplatin and its cationic species formed at pH 7.4 in low chloride concentrations were tested for their ability to induce phase changes in model membranes with different lipid compositions. Fluorescent probes that partition to different lipid phases were used to report on the fluidity of the membrane, and a leakage assay was performed to evaluate the effect of cisplatin in the permeability of these vesicles. The results showed that platinum(II) complex effects on membrane fluidity depend on membrane lipid composition and properties, promoting a stronger decrease in the fluidity of membranes containing gel phase. Moreover, at high concentration, these complexes were prone to alter the permeability of lipid membranes without inducing their collapse or aggregation.

摘要

越来越多的证据表明,脂质在细胞对铂(II)配合物的毒性和耐药机制中起着关键作用。特别是,顺铂和其他类似物被报道与脂质相互作用,并在大块膜和特定膜区域中短暂地促进脂质相变化。然而,这些过程很复杂,尚未完全理解。在这项工作中,研究了在低氯离子浓度下 pH 值为 7.4 时形成的顺铂及其阳离子物种,以测试它们在不同脂质组成的模型膜中诱导相变化的能力。用于报告膜流动性的荧光探针被用于报告膜的流动性,并且进行了渗漏测定以评估顺铂对这些囊泡通透性的影响。结果表明,铂(II)配合物对膜流动性的影响取决于膜脂质组成和性质,促进了含有凝胶相的膜流动性的更强降低。此外,在高浓度下,这些配合物易于改变脂质膜的通透性,而不会诱导其崩溃或聚集。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/8765417c9e2e/mp2c00321_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/ae020630e680/mp2c00321_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/4fb17546f621/mp2c00321_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/2e9d7650eae5/mp2c00321_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/bab672c46f1e/mp2c00321_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/61423d3dda8c/mp2c00321_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/8765417c9e2e/mp2c00321_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/ae020630e680/mp2c00321_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/4fb17546f621/mp2c00321_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/2e9d7650eae5/mp2c00321_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/bab672c46f1e/mp2c00321_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/61423d3dda8c/mp2c00321_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dc/9906771/8765417c9e2e/mp2c00321_0007.jpg

相似文献

[1]
Effect of Cisplatin and Its Cationic Analogues in the Phase Behavior and Permeability of Model Lipid Bilayers.

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[2]
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[3]
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[4]
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引用本文的文献

[1]
Synthesis, Physicochemical Characterization, Biological Evaluation, In Silico and Molecular Docking Studies of Pd(II) Complexes with P, S-Donor Ligands.

Pharmaceuticals (Basel). 2023-5-29

本文引用的文献

[1]
Liquid-Ordered Phase Formation by Mammalian and Yeast Sterols: A Common Feature With Organizational Differences.

Front Cell Dev Biol. 2020-6-12

[2]
Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine.

Sci Rep. 2019-11-20

[3]
Differential effects of simvastatin on membrane organization and dynamics in varying phases.

Chem Phys Lipids. 2019-9-27

[4]
The asymmetry of plasma membranes and their cholesterol content influence the uptake of cisplatin.

Sci Rep. 2019-4-4

[5]
Mass Spectrometry Imaging Suggests That Cisplatin Affects Exocytotic Release by Alteration of Cell Membrane Lipids.

Anal Chem. 2018-7-6

[6]
A Novel Therapeutic Strategy for Cancer Using Phosphatidylserine Targeting Stearylamine-Bearing Cationic Liposomes.

Mol Ther Nucleic Acids. 2018-3-2

[7]
Phosphatidylserine: A cancer cell targeting biomarker.

Semin Cancer Biol. 2017-9-1

[8]
Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties.

Sci Rep. 2017-6-21

[9]
Ceramide-Induced Lamellar Gel Phases in Fluid Cell Lipid Extracts.

Langmuir. 2016-8-23

[10]
Chemotherapeutic response to cisplatin-like drugs in human breast cancer cells probed by vibrational microspectroscopy.

Faraday Discuss. 2016-6-23

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