Stealth Nanoparticles Grafted with Dense Polymer Brushes Display Adsorption of Serum Protein Investigated by Isothermal Titration Calorimetry.

Stealth Nanoparticles Grafted with Dense Polymer Brushes Display Adsorption of Serum Protein Investigated by Isothermal Titration Calorimetry.
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用密集的聚合物刷接枝的隐形纳米颗粒显示通过等温滴定量热法调查的血清蛋白的吸附。

DOI:
10.1021/acs.jpcb.8b02338
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发表时间:
2018-06-07
期刊:
The journal of physical chemistry. B
影响因子:
--
通讯作者:
Reimhult E
Reimhult E
中科院分区:
其他
文献类型:
--
作者:
Gal N;Schroffenegger M;Reimhult E

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核壳纳米粒子因其在生命科学中的现有和潜在应用而备受关注。通常,接枝一层致密的水合聚合物外壳,即聚合物刷,以提高功能性纳米颗粒的胶体稳定性,防止蛋白质吸附、聚集、细胞识别和摄取。直到最近,人们普遍认为,聚合物刷壳确实可以防止蛋白质的强烈结合,这导致了它们在体外和体内优越的“隐身”特性。我们使用t依赖等温滴定量热法对表征良好的单分散超顺磁性氧化铁纳米颗粒进行了表征,这些纳米颗粒具有可控的致密隐身聚合物刷壳,“隐身”核壳纳米颗粒显示出显著的吸引的放热和焓与血清蛋白的相互作用,尽管具有出色的胶体稳定性和可忽略不计的非特异性细胞摄取。在室温下,这一观察结果仅弱依赖于氧化铁芯直径和接枝隐形聚合物类型的变化:聚(乙二醇)、聚(乙基恶唑啉)、聚(异丙基恶唑啉)和聚(n -异丙基丙烯酰胺)。聚合物刷壳的临界溶液温度接近体温,与蛋白质的相互作用表现出强烈的温度依赖性,随着温度的升高,蛋白质的结合能显著增加。聚乙二醇化纳米粒子的相互作用化学计量学估计接近1:1,而较大的热响应纳米粒子的相互作用化学计量学估计高达10:1,而相互作用的平均自由能是焓驱动的,与弱氢键相当。
Core–shell nanoparticles receive much attention for their current and potential applications in life sciences. Commonly, a dense shell of hydrated polymer, a polymer brush, is grafted to improve colloidal stability of functional nanoparticles and to prevent protein adsorption, aggregation, cell recognition, and uptake. Until recently, it was widely assumed that a polymer brush shell indeed prevents strong association of proteins and that this leads to their superior “stealth” properties in vitro and in vivo. We show using T-dependent isothermal titration calorimetry on well-characterized monodisperse superparamagnetic iron oxide nanoparticles with controlled dense stealth polymer brush shells that “stealth” core–shell nanoparticles display significant attractive exothermic and enthalpic interactions with serum proteins, despite having excellent colloidal stability and negligible nonspecific cell uptake. This observation is at room temperature shown to depend only weakly on variation of iron oxide core diameter and type of grafted stealth polymer: poly(ethylene glycol), poly(ethyl oxazoline), poly(isopropyl oxazoline), and poly(N-isopropyl acrylamide). Polymer brush shells with a critical solution temperature close to body temperature showed a strong temperature dependence in their interactions with proteins with a significant increase in protein binding energy with increased temperature. The stoichiometry of interaction is estimated to be near 1:1 for PEGylated nanoparticles and up to 10:1 for larger thermoresponsive nanoparticles, whereas the average free energy of interaction is enthalpically driven and comparable to a weak hydrogen bond.
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