There is increasing evidence that different phospholipids are involved in regulation of various cell processes and cell-cell interactions. Lysophospholipids (lysophosphatidic acid, lysophosphatidylcholine) and a number of lysosphingolipids play particular roles in these regulations. Their effects are mediated by specific G-protein-coupled receptors. G-Protein coupled signal transduction to the cell nucleus involving a chain of intracellular protein kinases induces the main effects in cells--growth, proliferation, survival, or apoptosis. This review summarizes recent data on various groups of lysophospholipid receptors and their cell signal transduction pathways.
Photodynamic therapy is an advanced method of treating cancer and various benign diseases, including infections. It uses light‐activated molecules [photosensitizers (PSs)] to generate reactive oxygen species (
ROS
) when irradiated with light of a specific wavelength. This study examined the photophysical and photosensitizing activity of the PS chlorin e6 incorporated in a delivery system based on plant phospholipids. This new nanoform of chlorin e6 comprised particles with a diameter of 18.4 ± 2.5 nm and zeta potential of −34.6 ± 3.0 mV. Incorporation of chlorin e6 in phospholipid nanoparticles was observed to cause a bathochromic shift of Q‐band absorption maximum by 14 nm without an absorption change in the range of the Soret band. Fluorescence intensity of chlorin e6 embedded in the phospholipid nanoparticles increased 1.7‐fold. Chlorin e6 in phospholipid nanoparticles, when irradiated, was able to generate
ROS
as shown by oxidation of polyunsaturated fatty acids of the phospholipid matrix of the delivery system and reduced
l
‐glutathione.
In vivo
it was demonstrated that the new nanoform of chlorin e6 provides more accumulation of PSs in tumor tissue than its free form. Moreover, its accumulation in the skin was lower and its elimination from the skin almost five times faster than when administered in free form. The observed differences of this new nanoform of chlorin e6 should lead to enhancement of antitumor efficacy and a decrease in phototoxicity.
This review considers various functional aspects of cell sphingolipids (sphingomyelin, ceramides) and lysosphingolipids (sphingosine-1-phosphate (S1P) and sphingosine phosphorylcholine). Good evidence now exists that they are actively involved in numerous cell-signaling processes. The enzymes responsible for formation and interconversion of cell sphingolipids (sphingomyelinases, ceramidase, sphingosine kinase, S1P-lyase) exhibit high sensitivity to various stimulating factors. This determines the content of individual cell sphingolipids and therefore the mode of cell response. Special attention is paid to preferential localization of sphingolipids in the rigid plasma membrane domains (rafts) coupled to many signal proteins. The suggestion is discussed that ceramide signaling may be based on the modification of fine molecular interactions in lipid rafts, resulting in its clusterization inducing the signal transduction. The review also highlights involvement of sphingolipids in cell proliferation, apoptosis, and in processes implicated to atherosclerosis.
The conditions for the preparation of a drug formulations based on the lipid derivative of sarcolysin embedded in phospholipid nanoparticles have been optimized. The drug is an ultra-thin emulsion with a light transmittance above 80% and a particle size of not more than 50 nm. It should be noted that 99% of the lipid derivative of sarcolysin are incorporated into phospholipid nanoparticles. Preservation of aggregation stability in the aquatic environment was observed for at least 2 days. In vitro experiments have shown that sarcolysin, introduced as a part of phospholipid nanoparticles, is distributed among lipoproteins and protein components of plasma. Moreover, the content of sarcolysin in all fractions involved in the transport of biologically active substances in the body, is significantly higher in case of prodrug administration (lipid derivative of sarcolysin) in the composition of phospholipid nanoparticles than, as compared with administration of a free form (pharmacological substances) to the incubation medium. The transformation of a prodrug into the drug sarcolysin occurs in the blood cells.
Quantum dots (QDs) are nanosized semiconductor crystals. They are currently applied in different science fields such as medicine, namely, cancer diagnostics and treatment. QD toxicity is caused by the toxicity of their components. In vivo application of QDs requires their toxicity assessment, so the purpose of this work has been the estimation of acute and chronic toxicity of the QDs at Danio rerio embryos and larvae, QDs being composed of CdSe/CdS/ZnS/S,S-dihydrolipoic acid/polyacrylic acid. We have found no QD acute toxicity during 48 hours of QDs action at the embryo up to the concentration of 185 µM Cd. QDs have been found to be toxic only at 5-7 days of action, it shows that QDs act accumulatively. Beside lethality, we have observed different larval development defects, that is, differently localized edemas, lag of development, tail curvature, and swimming bladder malformation. Our experimental data as well as literature data show that toxicity of the quantum dots at Danio rerio embryos and larvae is primarily caused by toxic action of Cd 2+ ion which arises from partial dissociation of CdSe and CdS molecules.
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