Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Characterization of Folic Acid and Poly(amidoamine) Dendrimer Interactions with Folate Binding Protein: A Force-Pulling Study

Journal Article · · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry
 [1];  [2];  [3];  [4];  [4];  [3];  [5];  [1]
  1. Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Chemistry
  2. Xavier Univ., New Orleans, LA (United States). Dept. of Chemistry
  3. Calvin College, Grand Rapids, MI (United States). Dept. of Chemistry & Biochemistry
  4. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical and Life Sciences Division
  5. Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Physics
In this paper, atomic force microscopy force-pulling experiments have been used to measure the binding forces between folic acid (FA) conjugated poly(amidoamine) (PAMAM) dendrimers and folate binding protein (FBP). The generation 5 (G5) PAMAM conjugates contained an average of 2.7, 4.7, and 7.2 FA per dendrimer. The most probable rupture force was measured to be 83, 201, and 189 pN for G5-FA2.7, G5-FA4.7, and G5-FA7.2, respectively. Folic acid blocking experiments for G5-FA7.2 reduced the frequency of successful binding events and increased the magnitude of the average rupture force to 274 pN. Finally, the force data are interpreted as arising from a network of van der Waals and electrostatic interactions that form between FBP and G5 PAMAM dendrimer, resulting in a binding strength far greater than that expected for an interaction between FA and FBP alone.
Research Organization:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Organization:
USDOE; National Inst. of Health (NIH) (United States)
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1458700
Report Number(s):
LLNL-JRNL--742632; 896737
Journal Information:
Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry, Journal Name: Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry Journal Issue: 35 Vol. 119; ISSN 1520-6106
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English

References (40)

Design of Folic Acid‐Conjugated Nanoparticles for Drug Targeting journal November 2000
Targeted and pH-Responsive Delivery of Doxorubicin to Cancer Cells Using Multifunctional Dendrimer-Modified Multi-Walled Carbon Nanotubes journal February 2013
Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis journal August 2011
Targeted Tumor Computed Tomography Imaging Using Low-Generation Dendrimer-Stabilized Gold Nanoparticles journal March 2013
Single and multiple bonds in (strept)avidin-biotin interactions journal April 2011
Why I believe nanoparticles are crucial as a carrier for targeted drug delivery journal April 2013
Stopped-Flow Kinetic Studies of the Interaction of Bovine Folate Binding Protein (FBP) and Folate journal October 2006
Dynamic strength of molecular adhesion bonds journal April 1997
Slow-binding inhibition: the general case journal November 1996
Encapsulation of 2-methoxyestradiol within multifunctional poly(amidoamine) dendrimers for targeted cancer therapy journal April 2011
Targeted CT/MR dual mode imaging of tumors using multifunctional dendrimer-entrapped gold nanoparticles journal July 2013
Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for in vivo tumor MR imaging journal November 2013
Folate-targeted therapeutic and imaging agents for cancer journal June 2009
Folate binding protein—Outlook for drug delivery applications journal April 2015
The Binding Avidity of a Nanoparticle-Based Multivalent Targeted Drug Delivery Platform journal January 2007
Structural and dynamic investigation of bovine folate receptor alpha (FOLR1), and role of ultra-high temperature processing on conformational and thermodynamic characteristics of FOLR1–folate complex journal September 2014
Prolonged blood circulation and enhanced tumor accumulation of folate-targeted dendrimer-polymer hybrid nanoparticles journal October 2014
Force Spectroscopy of Multivalent Binding of Riboflavin-Conjugated Dendrimers to Riboflavin Binding Protein journal April 2015
Discovery and Development of Folic-Acid-Based Receptor Targeting for Imaging and Therapy of Cancer and Inflammatory Diseases journal January 2008
Specific Antitumor Targetable β-Cyclodextrin−Poly(ethylene Glycol)−Folic Acid Drug Delivery Bioconjugate journal August 2004
Interaction of Poly(amidoamine) Dendrimers with Supported Lipid Bilayers and Cells:  Hole Formation and the Relation to Transport journal July 2004
Development of Tumor-Targeted Near Infrared Probes for Fluorescence Guided Surgery journal May 2013
Targeting Folate Receptor with Folate Linked to Extremities of Poly(ethylene glycol)-Grafted Liposomes:  In Vitro Studies journal March 1999
PAMAM Dendrimer-Based Multifunctional Conjugate for Cancer Therapy:  Synthesis, Characterization, and Functionality journal February 2006
Avidity Modulation of Folate-Targeted Multivalent Dendrimers for Evaluating Biophysical Models of Cancer Targeting Nanoparticles journal June 2013
Affinity and Rate Constants for Interactions of Bovine Folate-Binding Protein and Folate Derivatives Determined by Optical Biosensor Technology. Effect of Stereoselectivity journal June 2005
The AFM Measured Force Required to Rupture the Dithiolate Linkage of Thioctic Acid to Gold Is Less than the Rupture Force of a Simple Gold−Alkyl Thiolate Bond journal December 2005
Polyvalent Dendrimer-Methotrexate as a Folate Receptor-Targeted Cancer Therapeutic journal August 2012
Avidity Mechanism of Dendrimer–Folic Acid Conjugates journal April 2014
Poly(amidoamine) Dendrimer–Methotrexate Conjugates: The Mechanism of Interaction with Folate Binding Protein journal April 2014
Design and Function of a Dendrimer-Based Therapeutic Nanodevice Targeted to Tumor Cells Through the Folate Receptor journal January 2002
Structural basis for molecular recognition of folic acid by folate receptors journal July 2013
Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results journal September 2011
Targeted tumor CT imaging using folic acid-modified PEGylated dendrimer-entrapped gold nanoparticles journal January 2013
α Isoforms of soluble and membrane-linked folate-binding protein in human blood journal June 2008
Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition journal August 2013
Kinetic Limitations of Cooperativity-Based Drug Delivery Systems journal April 2008
Optical imaging of metastatic tumors using a folate-targeted fluorescent probe journal January 2003
Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer journal June 2005
A Chemometric Analysis of Ligand-Induced Changes in Intrinsic Fluorescence of Folate Binding Protein Indicates a Link between Altered Conformational Structure and Physico-Chemical Characteristics journal December 2009

Cited By (4)

Understanding Effects of PAMAM Dendrimer Size and Surface Chemistry on Serum Protein Binding with Discrete Molecular Dynamics Simulations journal July 2018
Self-assembling asymmetric peptide-dendrimer micelles – a platform for effective and versatile in vitro nucleic acid delivery journal March 2018
Dendrimer-based nanocarriers: a versatile platform for drug delivery: Dendrimer-based nanocarriers journal April 2016
Synthesis and preliminary evaluation of a 99m Tc-labeled folate-PAMAM dendrimer for FR imaging journal December 2016

Similar Records

Folate-binding protein and the absorption of folic acid in the small intestine of the suckling rat
Journal Article · Thu Sep 01 00:00:00 EDT 1988 · Am. J. Clin. Nutr.; (United States) · OSTI ID:7095404

Mechanistic studies of in vitro cytotoxicity of poly(amidoamine) dendrimers in mammalian cells
Journal Article · Mon Nov 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology · OSTI ID:21460231

Poly(amidoamine) dendrimers: A new class of high capacity chelating agents for Cu(II) ions
Journal Article · Sun Feb 28 23:00:00 EST 1999 · Environmental Science and Technology · OSTI ID:335332