Interactions of Poly(amidoamine) Dendrimers with Human Serum Albumin: Binding Constants and Mechanisms

Cited 92 time in webofscience Cited 0 time in scopus
  • Hit : 461
  • Download : 0
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 (Kb) of PAMAM dendrimers depend on dendrimer size and terminal group chemistry. The NMR 1H and DOSY experiments indicate that the interactions between HSA and PAMAM dendrimers are relatively weak. The 1H NMR STD experiments and MD simulations suggest that the inner shell protons of the dendrimers group:; interact more strongly with HSA proteins. These interactions, which are consistently observed for different dendrimer generations (G0-NH(2) vs 64-NH(2)) and terminal groups (G4-NH(2) vs 64-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).
Publisher
AMER CHEMICAL SOC
Issue Date
2011-05
Language
English
Article Type
Article
Keywords

DIFFUSION-ORDERED SPECTROSCOPY; TRANSFER DIFFERENCE NMR; COPOLYMER NANOPARTICLES; CRYSTAL-STRUCTURE; PROTEIN-BINDING; PLASMA-PROTEINS; CHEMISTRY; SURFACES; ACID; SIZE

Citation

ACS NANO, v.5, no.5, pp.3456 - 3468

ISSN
1936-0851
DOI
10.1021/nn1021007
URI
http://hdl.handle.net/10203/94971
Appears in Collection
EEW-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 92 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0