Department of Chemistry, University of California, Irvine, Irvine, California 92697, USA.
J Am Chem Soc. 2012 Feb 8;134(5):2681-90. doi: 10.1021/ja209959t. Epub 2012 Jan 26.
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 the main component of a polymer nanoparticle 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.
合成聚合物纳米粒子（NPs）与生物大分子（如蛋白质、脂质和多糖）之间的相互作用可以深刻影响 NPs 的命运和功能。多糖（如肝素/硫酸肝素）是细胞表面和细胞外基质的重要组成部分，在许多生物过程中发挥着关键作用。我们通过 ITC、SPR 和抗凝剂测定系统地研究了合成聚合物纳米粒子与多糖之间的相互作用，为生物医学应用的纳米粒子工程提供了指导。丙烯酰胺纳米粒子（~30nm）与肝素之间的相互作用主要由焓驱动，亲和力为亚微摩尔级。氢键、离子相互作用和极性基团的去水合被确定为亲和力的关键贡献。已经发现，NP 的高电荷密度和交联可以有助于高亲和力。肝素的亲和力和结合容量可以通过增加盐浓度显著降低，而仅略微随温度升高而降低。当聚合物纳米粒子的主要成分从丙烯酰胺（焓驱动）变为 N-异丙基丙烯酰胺（熵驱动）时，观察到结合热力学的显著差异。这种热力学的变化导致这两种类型的聚合物 NPs 对盐浓度和温度的反应不同。还表明，某些合成聚合物纳米粒子可以抑制蛋白质-肝素相互作用，从而为治疗应用提供了潜力。
