Abstract
The aim of this study was to evaluate the nature and mechanisms of interaction between HIV peptide/dendrimer complexes (dendriplex) and artificial lipid membranes, such as large unilayered vesicles (LUV) and lipid monolayers in the air–water interface. Dendriplexes were combined as one of three HIV-derived peptides (Gp160, P24 and Nef) and one of two cationic phosphorus dendrimers (CPD-G3 and CPD-G4). LUVs were formed of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) or of a mixture of DMPC and dipalmitoyl-phosphatidylglycerol (DPPG). Interactions between dendriplexes and vesicles were characterized by dynamic light scattering (DLS), fluorescence anisotropy, differential scanning calorimetry (DSC) and Langmuir–Blodgett methods. The morphology of formed systems was examined by transmission electron microscopy (TEM). The results suggest that dendriplexes interact with both hydrophobic and hydrophilic regions of lipid bilayers. The interactions between dendriplexes and negatively charged lipids (DMPC–DPPG) were stronger than those between dendriplexes and liposomes composed of zwitterionic lipids (DMPC). The former were primarily of electrostatic nature due to the positive charge of dendriplexes and the negative charge of the membrane, whereas the latter can be attributed to disturbances in the hydrophobic domain of the membrane. Obtained results provide new information about mechanisms of interaction between lipid membranes and nanocomplexes formed with HIV-derived peptides and phosphorus dendrimers. These data could be important for the choosing the appropriate antigen delivery vehicle in the new vaccines against HIV infection.
Highlights
The aim of this study was to evaluate the nature and mechanisms of interaction between Human immunodeficiency virus (HIV) peptide/ dendrimer complexes and artificial lipid membranes, such as large unilayered vesicles (LUV) and lipid monolayers in the air–water interface
In order to model the interaction between HIV peptide/dendrimer complexes with a cell membrane, the liposomes of different lipid composition: (a) DMPC; (b) DMPC/DPPG were used
The hydrodynamic diameters of the DMPC or DMPC/DPPG liposomes were 116.5 ± 2.5 and 118.2 ± 1.8 nm, respectively, which is in good agreement with the diameter of the polycarbonate filter used for liposome preparation
Summary
The aim of this study was to evaluate the nature and mechanisms of interaction between HIV peptide/ dendrimer complexes (dendriplex) and artificial lipid membranes, such as large unilayered vesicles (LUV) and lipid monolayers in the air–water interface. Obtained results provide new information about mechanisms of interaction between lipid membranes and nanocomplexes formed with HIV-derived peptides and phosphorus dendrimers. These data could be important for the choosing the appropriate antigen delivery vehicle in the new vaccines against HIV infection. A promising approach to improving the deteriorated immune function in HIV-1-infected individuals may be the application of dendritic cells (DCs) as a vaccine adjuvant. Dynamic light scattering, Doppler laser velocimetry, Langmuir–Blodgett technique and transmission electron microscopy, we found that both types of dendriplexes interact with model membranes, resulting in increases of fluorescence anisotropy, liposome size and surface pressure. There was an increase of zeta potential from negative to positive values, especially for negatively charged vesicles composed of DMPC–DPPG (9:1 mol/mol)
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