The influence of an antitumor lipid - erucylphosphocholine - on artificial lipid raft system modeled as Langmuir monolayer.

Outer layer of cellular membrane contains ordered domains enriched in cholesterol and sphingolipids, called 'lipid rafts', which play various biological roles, i.e., are involved in the induction of cell death by apoptosis. Recent studies have shown that these domains may constitute binding sites for selected drugs. For example alkylphosphocholines (APCs), which are new-generation antitumor agents characterized by high selectivity and broad spectrum of activity, are known to have their molecular targets located at cellular membrane and their selective accumulation in tumor cells has been hypothesized to be linked with the alternation of biophysical properties of lipid rafts. To get a deeper insight into this issue, interactions between representative APC: erucylphosphocholine, and artificial lipid raft system, modeled as Langmuir monolayer (composed of cholesterol and sphingomyelin mixed in 1:2 proportion) were investigated. The Langmuir monolayer experiments, based on recording surface pressure-area isotherms, were complemented with Brewster angle microscopy results, which enabled direct visualization of the monolayers structure. In addition, the investigated monolayers were transferred onto solid supports and studied with AFM. The interactions between model raft system and erucylphosphocholine were analyzed qualitatively (with mean molecular area values) as well as quantitatively (with ΔG(exc) function). The obtained results indicate that erucylphosphocholine introduced to raft-mimicking model membrane causes fluidizing effect and weakens the interactions between cholesterol and sphingomyelin, which results in phase separation at high surface pressures. This leads to the redistribution of cholesterol molecules in model raft, which confirms the results observed in biological studies.

Affinity of alkylphosphocholines to biological membrane of prostate cancer: studies in natural and model systems.

The effectiveness of two alkylphosphocholines (APCs), hexadecylphosphocholine (miltefosine) and erucylphosphocholine to combat prostate cancer has been studied in vitro with artificial cancerous membrane, modelled with the Langmuir monolayer technique, and on cell line (Du-145). Studies performed with the Langmuir method indicate that both the investigated drugs have the affinity to the monolayer mimicking prostate cancer membrane (composed of cholesterol:POPC = 0.428) and the drug-membrane interactions are stronger for erucylphosphocholine as compared to hexadecylphosphocholine. Moreover, both studied drugs were found to fluidize the model membrane, which may lead to apoptosis. Indeed, biological studies confirmed that in Du-145 cell line both investigated alkylphosphocholines cause cell death primarily by apoptosis while necrotic cells constitute only a small percentage of APC-treated cells.

Interactions of alkylphosphocholines with model membranes-the Langmuir monolayer study.

Alkylphosphocholines (APCs) belong to a class of synthetic antitumor lipids, which are new-generation anticancer agents. In contrast to traditional antitumor drugs, they do not attack the cell nucleus but, rather, the cellular membrane; however, their mechanism of action is not fully understood. This work compared the interactions of selected APCs [namely, hexadecylphosphocholine (miltefosine), octadecylphosphocholine and erucylphosphocholine] with the most important membrane lipids [cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)] and examined their influence on a model membrane of tumor and normal cells. As a simple model of membranes, Langmuir monolayers prepared by mixing cholesterol either with a saturated phosphatidylcholine (DPPC), for a normal cell membrane, or with an unsaturated one (POPC), for a tumor cell membrane, have been applied. The APC-lipid interactions, based on experimental surface pressure (π) versus mean molecular area (A) isotherms, were analyzed qualitatively (with mean molecular area values) as well as quantitatively (with the ΔG(exc) function). Strong attractive interactions were observed for mixtures of APCs with cholesterol, contrary to the investigated phosphatidylcholines, for which the interactions were found to be weak with a tendency to separation of film components. In ternary monolayers it has been found that the investigated model systems (cholesterol/DPPC/APC vs cholesterol/POPC/APC) differ significantly as regards the interactions between film-forming molecules. The results demonstrate stronger interactions between the components of cholesterol/POPC/APC monolayers compared to cholesterol/POPC film, mimicking tumor cell membranes. In contrast, the interactions in cholesterol/DPPC/APC films were found to be weaker than those in the cholesterol/DPPC system, serving as a model of healthy cell membranes, thus proving that the incorporation of APCs is, from a thermodynamic point of view, unfavorable for binary cholesterol/DPPC monolayers. It can be concluded that the composition of healthy cell membranes is a natural barrier preventing the incorporation of APCs into normal cells.

Structural, electrical, and magnetic study of La-, Eu-, and Er- doped bismuth ferrite nanomaterials obtained by solution combustion synthesis.

In this work, the multiferroic bismuth ferrite materials Bi0.9RE0.1FeO3 doped by rare-earth (RE = La, Eu, and Er) elements were obtained by the solution combustion synthesis. Structure, electrical, and magnetic properties of prepared samples were investigated by X-ray photoelectron spectroscopy, Mössbauer spectroscopy, electrical hysteresis measurement, broadband dielectric spectroscopy, and SQUID magnetometry. All obtained nanomaterials are characterized by spontaneous electrical polarization, which confirmed their ferroelectric properties. Investigation of magnetic properties at 300.0 K and 2.0 K showed that all investigated Bi0.9RE0.1FeO3 ferrites possess significantly higher magnetization in comparison to bismuth ferrites obtained by different methods. The highest saturation magnetisation of 5.161 emu/g at 300.0 K was observed for the BLaFO sample, while at 2.0 K it was 12.07 emu/g for the BErFO sample. Several possible reasons for these phenomena were proposed and discussed.