Synthetic Polymer Nanoparticle–Polysaccharide Interactions: A Systematic Study

Abstract

The interaction between synthetic polymer nanoparticles (NPs) and biomacromolecules (e.g. proteins, lipids and polysaccharides) can profoundly influence the NPs fate and function. Polysaccharides (e.g. heparin/heparin sulfate) are a key component of cell surfaces and the extracelluar matrix and play critical roles in many biological processes. We report a systematic investigation of the interaction between synthetic polymer nanoparticles and polysaccharides by ITC, SPR and an anticoagulant assay to provide guidelines to engineer nanoparticles for biomedical applications. The interaction between acrylamide nanoparticles (~30 nm) and heparin is mainly enthalpy driven with submicromolar affinity. Hydrogen bonding, ionic interactions and dehydration of polar groups are identified to be key contributions to the affinity. It has been found that high charge density and cross linking of the NP can contribute to high affinity. The affinity and binding capacity of heparin can be significantly diminished by an increase in salt concentration while only slightly decreased with an increase of temperature. A striking difference in binding thermodynamics has been observed when polymer nanoparticle’s main component is changed from acrylamide (enthalpy driven) to N-isopropylacryalmide (entropy driven). This change in thermodynamics leads to different responses of these two types of polymer NPs to salt concentration and temperature. Select synthetic polymer nanoparticles have also been shown to inhibit protein-heparin interactions and thus offer the potential for therapeutic applications.

Biomolecular coronas provide the biological identity of nanosized materials

“…The hard corona structure can also be studied by isolating the particle-corona , surface plasmon resonance 32,86,92 , small angle X-ray scattering 67,91,93 , quartz crystal microbalance 94 , isothermal titration calorimetry 86,93,95 , UV-vis and fluorescence spectroscopies 68,96 . Adsorption on the nanoparticle surface may result in protein conformational changes, and these have been studied by circular dichroism 6, 67,68,72,80 , infrared spectroscopy 69,80 , NMR 85,97 , and enzyme activity assays 67,68,98 .…”

Preparation of protein imprinted materials by hierarchical imprinting techniques and application in selective depletion of albumin from human serum

“…Although MIPs for small molecules recognition have been successfully applied in solid-phase extraction (SPE), chiral separation, chemical sensor, enzyme-like catalysis, drug delivery and library screening, the preparation of biomacromolcule, such as proteins, imprinted polymers are rather difficult45678. The traditional molecular imprinting polymers were prepared by bulk imprinting.…”

Preparation of abiotic polymer nanoparticles for sequestration and neutralization of a target peptide toxin

“…We and other groups have synthesized a number of pNIPAm-based polymer particles that contain a range of functional comonomers, and we evaluated their binding affinity against target biomacromolecules 8,11,[26][27][28][32][33][34][35][36][37][38][39][40][41] . These polymer NPs have been applied in areas that include inhibition of amyloid fibril formation 35,36 , sample preparation for biomarker analysis 37 , toxin neutralization 8,9,11 , drug delivery 38,39 , protein purification 12,26,28 and protein stabilization 42 .…”