title: Interactions of poly(amidoamine) dendrimers with human serum albumin: binding constants and mechanisms.
abstract: The interactions of nanomaterials with plasma proteins have a significant impact on their in vivo transport and fate in biological fluids. This article discusses the binding of human serum albumin (HSA) to poly(amidoamine) [PAMAM] dendrimers. We use protein-coated silica particles to measure the HSA binding constants (K(b)) of a homologous series of 19 PAMAM dendrimers in aqueous solutions at physiological pH (7.4) as a function of dendrimer generation, terminal group, and core chemistry. To gain insight into the mechanisms of HSA binding to PAMAM dendrimers, we combined (1)H NMR, saturation transfer difference (STD) NMR, and NMR diffusion ordered spectroscopy (DOSY) of dendrimer-HSA complexes with atomistic molecular dynamics (MD) simulations of dendrimer conformation in aqueous solutions. The binding measurements show that the HSA binding constants (K(b)) of PAMAM dendrimers depend on dendrimer size and terminal group chemistry. The NMR (1)H and DOSY experiments indicate that the interactions between HSA and PAMAM dendrimers are relatively weak. The (1)H NMR STD experiments and MD simulations suggest that the inner shell protons of the dendrimers groups interact more strongly with HSA proteins. These interactions, which are consistently observed for different dendrimer generations (G0-NH(2)vs G4-NH(2)) and terminal groups (G4-NH(2)vs G4-OH with amidoethanol groups), suggest that PAMAM dendrimers adopt backfolded configurations as they form weak complexes with HSA proteins in aqueous solutions at physiological pH (7.4).
authors: Materials and Process Simulation Center, Division of Chemistry and Chemical Engineering, California Institute of Technology, USA.
authors: Jyotsnendu
authors: J
authors: Giri
authors: Mamadou S
authors: MS
authors: Diallo
authors: André J
authors: AJ
authors: Simpson
authors: Yi
authors: Y
authors: Liu
authors: William A
authors: WA
authors: Goddard
authors: Rajeev
authors: R
authors: Kumar
authors: Gwen C
authors: GC
authors: Woods
mesh_terms: D001665:Binding Sites; D050091:Dendrimers / Q000737:chemistry*; D008422:Materials Testing; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D012709:Serum Albumin