Interaction of cationic carbosilane dendrimers and their complexes with siRNA with erythrocytes and red blood cell ghosts

Abstract

We have investigated the interactions between cationic NN16 and BDBR0011 carbosilane dendrimers with red blood cells or their cell membranes. The carbosilane dendrimers used possess 16 cationic functional groups. Both the dendrimers are made of water-stable carbon-silicon bonds, but NN16 possesses some oxygen-silicon bonds that are unstable in water. The nucleic acid used in the experiments was targeted against GAG-1 gene from the human immunodeficiency virus, HIV-1. By binding to the outer leaflet of the membrane, carbosilane dendrimers decreased the fluidity of the hydrophilic part of the membrane but increased the fluidity of the hydrophobic interior. They induced hemolysis, but did not change the morphology of the cells. Increasing concentrations of dendrimers induced erythrocyte aggregation. Binding of short interfering ribonucleic acid (siRNA) to a dendrimer molecule decreased the availability of cationic groups and diminished their cytotoxicity. siRNA-dendrimer complexes changed neither the fluidity of biological membranes nor caused cell hemolysis. Addition of dendriplexes to red blood cell suspension induced echinocyte formation.

Keywords: Carbosilane; HIV-1; Hemolysis; Membrane fluidity; Red blood cell ghost; siRNA.

Graphical abstract

Fig. 1

Structure of carbosilane dendrimers; (A) NN16; (B) BDBR0011.

Fig. 2

Fluorescence anisotropy of TMA-DPH (A) and DPH (B) in cell membrane; ■—NN16 dendrimer, ●—BDBR0011 dendrimer. All data were expressed as mean ± S.E.M. n = 4; * p < 0.05 for each point vs control.

Fig. 3

Fluorescence anisotropy of TMA-DPH (A) and DPH (B) in cell membrane; ■—NN16 dendrimer/siRNA, ●—BDBR0011 dendrimer/siRNA. All data were expressed as mean ± S.E.M. n = 4; * p < 0.05 for each point vs control.

Fig. 4

Red blood cell hemolysis; (A) ■—NN16 dendrimer, ●—BDBR0011 dendrimer; (B) □—NN16 dendrimer/siRNA, ○—BDBR0011 dendrimer/siRNA. All data were expressed as mean ± S.E.M. n = 4; * p < 0.05 for each point vs control.

Fig. 5

Erythrocytes morphology changes; NN16 dendrimer, BDBR0011 dendrimer.

Fig. 6

Erythrocytes morphology changes; NN16 dendrimer/siRNA, BDBR0011 dendrimer/siRNA.