Molecular Mechanisms of the Adsorption of a Model Protein (Human Serum Albumin) on Poly(Methylidene Malonate 2.1.2) Nanoparticles |
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Authors: | Bousquet Yoléne Swart Pieter J Schmitt-Colin Nathalie Velge-Roussel Florence Kuipers Mirjam E Meijer Dirk K F Bru Nicole Hoebeke Johan Breton Pascal |
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Institution: | (1) Halisol S.A., Paris, France;(2) Department of Pharmacokinetics and Drug Delivery, Groningen Utrecht Institute for Drug Exploration (GUIDE), Groningen, The Netherlands;(3) CJF93/09 INSERM "Immunologie des Maladies Parasitaires UFR Sciences Pharmaceutiques, Université François Rabelais, Tours, France |
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Abstract: | Purpose. To understand the molecular mechanisms involved in protein–methylidene malonate 2.1.2 polymer interactions.
Methods. To assess the importance of electrostatic forces in polymer-protein interactions use was made of HAS and its derivatives, which were anionized by succinylation and aconitylation. Surface plasmon resonance measurements, using the three HSA molecules as immobilized ligands and polymer nanoparticles as analytes in the liquid phase, allowed the determination of initial kinetic constants and affinity constants at equilibrium at two different temperatures.
Results. Saturation of binding for the three proteins occurred at approximately 900 protein molecules/nanoparticle. The apparent affinity decreased with increasing electronegativity of the proteins. Surface plasmon resonance measurement of proteins, covalently linked to the chip matrix, showed a high affinity for the nanoparticles (KA 1010 M-1) and confirmed the moderate decrease of affinity with increasing electronegativity of the modified albumins. Measurements at 25 and 37°C showed no significant increase in the albumin-nanoparticle interactions. Dissociation of the proteins from the nanoparticles could only be realized with chaotropic salt solutions.
Conclusions. These results suggest the molecular forces initiating the protein-nanoparticle interactions are mainly of electrostatic nature followed by stabilization by hydrophobic forces. The high affinity confirms the nanoparticles as excellent carriers for protein delivery. |
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Keywords: | nanoparticle methylidene malonate 2 1 2 protein-polymer interaction surface plasmon resonance (SPR) albumins |
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