Comparison of the effects of dendrimer, micelle and silver nanoparticles on phospholipase A2 structure.

The interaction of nanoparticles (NP) with proteins (the so-called 'protein corona') is a huge challenge in attempting to apply them in personalized nanomedicine. We have analyzed the interaction between A) two 'soft' NPs (a cationic phosphorus dendrimer of generation 3; a cationic phosphorus amphiphilic dendron of generation 2), and B) one 'hard' nanoparticle (silver NP covered with cationic carbosilane dendritic moieties); and membrane-bound protein phospholipase A2 from bovine pancreas. The hard and soft NPs have differences in the nature of their interactions with phospholipase A2. This enzyme surrounds hard AgNP, whereas dendrimer and amphiphilic dendron form aggregates/micelles with phospholipase A2. There is a difference in action of phospholipase A2 bound to the core of dendrimer, and of micelles formed from non-covalent interactions between the amphiphilic dendron. These data are important in understanding the nature of interaction between different kinds of nanoparticles and proteins.

Acidosis, magnesium and acetylsalicylic acid: effects on thrombin.

Thrombin, an enzyme from the hydrolase family, is the main component of the blood coagulation system. In ischemic stroke it acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin forming blood clots in the brain. It has been found to phosphoresce at room temperature in the millisecond and microsecond ranges. The phosphorescence of thrombin was studied under physiological conditions, in acidosis (decrease of pH from 8.0 to 5.0) and on the addition of salts (magnesium sulfate and sodium chloride) and of acetylsalicylic acid, and its connection with thrombin function is discussed. Acidosis significantly increased the internal dynamics of thrombin. We propose that lactate-acidosis plays a protective role in stroke, preventing the formation of clots. The addition of NaCl and MgSO(4) in different concentrations increased the internal dynamics of thrombin. Also, the addition of MgSO(4) decreased thrombin-induced platelet aggregation. However, magnesium sulfate and acetylsalicylic acid in the therapeutic concentrations used for treatment of ischemic stroke had no effect on thrombin internal dynamics. The data obtained will help to elucidate the conformational stability of thrombin under conditions modulating lactate-acidosis and in the presence of magnesium sulfate.