Investigation of miltefosine-model membranes interactions at the molecular level for two different PS levels modeling cancer cells.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-08-01 Epub Date: 2024-06-04 DOI:10.1007/s10863-024-10025-y
Züleyha Özçelik Çetinel, Duygu Bilge
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Abstract

Miltefosine (MLT) is a broad-spectrum drug included in the alkylphospholipids (APL) used against leishmania and various types of cancer. The most crucial feature of APLs is that they are thought to only kill cancerous cells without harming normal cells. However, the molecular mechanism of action of APLs is not completely understood. The increase in the phosphatidylserine (PS) ratio is a marker showing the stage of cancer and even metastasis. The goal of this research was to investigate the molecular effects of miltefosine at the molecular level in different PS ratios. The effects of MLT on membrane phase transition, membrane orders, and dynamics were studied using DPPC/DPPS (3:1) and DPPC/DPPS (1:1) multilayer (MLV) vesicles mimicking DPPS ratio variation, Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared spectroscopy (FTIR). Our findings indicate that miltefosine is evidence at the molecular level that it is directed towards the tumor cell and that the drug's effect increases with the increase of anionic lipids in the membrane depending on the stage of cancer.

Abstract Image

针对两种不同 PS 水平的癌细胞模型,研究米替福新与模型膜在分子水平上的相互作用。
米替福新(MLT)是烷基磷脂(APL)中的一种广谱药物,用于防治利什曼病和各种癌症。APL 的最大特点是被认为只能杀死癌细胞,而不会伤害正常细胞。然而,APLs 的分子作用机制尚未完全明了。磷脂酰丝氨酸(PS)比率的增加是显示癌症阶段甚至转移的标志。本研究旨在从分子水平研究不同磷脂酰丝氨酸比率下米替福新的分子效应。我们使用 DPPC/DPPS (3:1) 和 DPPC/DPPS (1:1) 多层 (MLV) 囊泡模拟 DPPS 比率变化、差示扫描量热法 (DSC) 和傅立叶变换红外光谱法 (FTIR) 研究了 MLT 对膜相变、膜秩和动力学的影响。我们的研究结果表明,米替福新在分子水平上证明了它是针对肿瘤细胞的,而且根据癌症的不同阶段,药物的作用会随着膜中阴离子脂质的增加而增强。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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