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

Giri, Jyotsnendu and Diallo, Mamadou S. and Simpson, André J. and Liu, Yi and Goddard, William A., III and Kumar, Rajeev and Woods, Gwen C. (2011) Interactions of Poly(amidoamine) Dendrimers with Human Serum Albumin: Binding Constants and Mechanisms. ACS Nano, 5 (5). pp. 3456-3468. ISSN 1936-0851 . https://resolver.caltech.edu/CaltechAUTHORS:20110607-094808686

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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 ^1H 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 ^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 groups interact more strongly with HSA proteins. These interactions, which are consistently observed for different dendrimer generations (G0-NH_2vs G4-NH_2) and terminal groups (G4-NH_2vs 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).


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/nn1021007DOIArticle
http://pubs.acs.org/doi/abs/10.1021/nn1021007PublisherArticle
ORCID:
AuthorORCID
Goddard, William A., III0000-0003-0097-5716
Additional Information:© 2011 American Chemical Society. Received for review August 20, 2010 and accepted March 25, 2011. Publication Date (Web): March 25, 2011. This work was carried out at the California Institute of Technology (Caltech) and the University of Toronto at Scarborough. Funding for the Caltech work was provided by the Environmental Protection Agency (EPA STAR Grant RD832525), the National Science Foundation (CBET NIRT Award 0506951), and the Oak Ridge National Laboratory (6400007192, LDRD 05125). Funding for the University of Toronto work (NMR experiments) was provided by Natural Sciences and Engineering Research Council of Canada (NSERC, Strategic and Discovery Programs) and the Government of Ontario in the form of an Early Researcher Award (A.J.S.). M.S. Diallo was also supported by the KAIST EEWS Initiative (NT080607C0209721). W. A. Goddard III was supported partially by the KAIST World Class University (WCU) program (NRF-31-2008-000-10055). Note Added after ASAP Publication: After this paper was published online April 1, 2011, a correction was made to the bottom panel of Figure 2, and the y-axes of Figures 2-4 were amended. The revised version was published April 12, 2011.
Funders:
Funding AgencyGrant Number
Environmental Protection Agency (EPA STAR)RD832525
NSFCBT-0506951
Oak Ridge National Laboratory6400007192
Oak Ridge National LaboratoryLDRD 05125
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
Government of Ontario UNSPECIFIED
Korea Advanced Institute of Science and Technology (KAIST)NT080607C0209721
Korea Advanced Institute of Science and Technology (KAIST)NRF-31-2008-000-10055
Subject Keywords:dendrimers; proteins; human serum albumin; nanobiotechnology; nantoxicology; NMR epitope mapping and atomistic molecular dynamics simulations
Issue or Number:5
Record Number:CaltechAUTHORS:20110607-094808686
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110607-094808686
Official Citation:Interactions of Poly(amidoamine) Dendrimers with Human Serum Albumin: Binding Constants and Mechanisms Jyotsnendu Giri, Mamadou S. Diallo, Andr J. Simpson, Yi Liu, William A. Goddard, III, Rajeev Kumar, and Gwen C. Woods pp 3456–3468 Publication Date (Web): March 25, 2011 (Article) DOI: 10.1021/nn1021007
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:23926
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:07 Jun 2011 17:28
Last Modified:03 Oct 2019 02:51

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