US EPA

4218492 

Journal Article 

Kinetic analysis of the interaction between poly(amidoamine) dendrimers and model lipid membranes 

Tiriveedhi, V; Kitchens, KM; Nevels, KJ; Ghandehari, H; Butko, P 

2011 

1 

Biochimica et Biophysica Acta
ISSN: 0006-3002
EISSN: 1878-2434 

ELSEVIER 

AMSTERDAM 

1808 

1 

209-218 

English 

20828535 

10.1016/j.bbamem.2010.08.017 

WOS:000285853800022 

We used fluorescence spectroscopy and surface tensiometry to study the interaction between low-generation (G1 and G4) poly(amidoamine) (PAMAM) dendrimers, potential vehicles for intracellular drug delivery, and model lipid bilayers. Membrane association of fluorescently labeled dendrimers, measured by fluorescence anisotropy, increased with increasing size of the dendrimer and with increasing negative charge density in the membrane, indicating the electrostatic nature of the interaction. When the membrane was doped with pyrene-labeled phosphatidyl glycerol (pyrene-PG), pyrene excimer fluorescence demonstrated a dendrimer-induced selective aggregation of negatively charged lipids when the membrane was in the liquid crystalline state. A nonlinear Stern-Volmer quenching of dendrimer fluorescence with cobalt bromide suggested a dendrimer-induced aggregation of lipid vesicles, which increased with the dendrimer's generation number. Surface tensiometry measurements showed that dendrimers penetrated into the lipid monolayer only at subphysiologic surface pressures (<30mN/m). We conclude that the low-generation PAMAM dendrimers associate with lipid membranes predominantly electrostatically, without significantly compromising the bilayer integrity. They bind stronger to membranes with higher fluidity and lower surface pressure, which are characteristic of rapidly dividing cells. 

Cell-penetrating molecules; Fluorescence spectroscopy; Membrane fluidity; PAMAM dendrimers; Quenching; Resonance energy transfer