Interaction of spin-labeled HPMA-based nanoparticles with human blood plasma proteins - the introduction of protein-corona-free polymer nanomedicine
Interaction of spin-labeled HPMA-based nanoparticles with human blood plasma proteins - the introduction of protein-corona-free polymer nanomedicine
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DOI：
10.1039/c7nr09355a
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发表时间：
2018-04-07
期刊：
影响因子：
6.7
通讯作者：
Filippov, Sergey K.
中科院分区：
文献类型：
--
作者：
Klepac, Damir;Kostkova, Hana;Filippov, Sergey K.
在本文中，我们修订了目前对静脉注射后血浆中纳米粒子表面产生的蛋白质电晕的理解。我们专注于具有经过验证的治疗效果的纳米颗粒。这些纳米粒子基于两种类型的基于 N-(2-羟丙基) 甲基丙烯酰胺 (HPMA) 的生物相容性两亲性共聚物：一种嵌段共聚物聚(ε-己内酯) (PCL)-b-聚(HPMA)，以及一种带有胆固醇部分的统计 HPMA 共聚物，这些共聚物已在体外和体内进行了测试。我们通过电子顺磁共振（EPR）、等温滴定量热法、动态光散射和低温透射电子显微镜研究了纳米粒子与血浆和选定血浆蛋白的相互作用。这些共聚物在疏水性 PCL 末端或沿着亲水性 HPMA 链用 TEMPO 自由基标记，以监测蛋白质吸附引起的聚合物链动力学变化。通过 EPR 和其他方法，我们能够探测纳米粒子和血液蛋白之间的特异性相互作用，特别是低密度和高密度脂蛋白、免疫球蛋白 G、人血清白蛋白 (HSA) 和人血浆。研究发现，单个蛋白质和血浆对纳米粒子的结合亲和力非常低。我们观察到基于 HPMA 的纳米粒子周围没有硬电晕；除 HSA 外，其他蛋白质均未显示出与纳米颗粒的可检测结合。我们的研究证实，经典的“硬电晕-软电晕”范例并不适用于所有类型的纳米粒子，并且每个系统都有一个由纳米粒子材料的性质决定的独特的蛋白质电晕。
In this paper, we revised the current understanding of the protein corona that is created on the surface of nanoparticles in blood plasma after an intravenous injection. We have focused on nanoparticles that have a proven therapeutic outcome. These nanoparticles are based on two types of biocompatible amphiphilic copolymers based on N-(2-hydroxypropyl) methacrylamide (HPMA): a block copolymer, poly(epsilon-caprolactone) (PCL)-b-poly(HPMA), and a statistical HPMA copolymer bearing cholesterol moieties, which have been tested both in vitro and in vivo. We studied the interaction of nanoparticles with blood plasma and selected blood plasma proteins by electron paramagnetic resonance (EPR), isothermal titration calorimetry, dynamic light scattering, and cryo-transmission electron microscopy. The copolymers were labeled with TEMPO radicals at the end of hydrophobic PCL or along the hydrophilic HPMA chains to monitor changes in polymer chain dynamics caused by protein adsorption. By EPR and other methods, we were able to probe specific interactions between nanoparticles and blood proteins, specifically low-and high-density lipoproteins, immunoglobulin G, human serum albumin (HSA), and human plasma. It was found that individual proteins and plasma have very low binding affinity to nanoparticles. We observed no hard corona around HPMA-based nanoparticles; with the exception of HSA the proteins showed no detectable binding to the nanoparticles. Our study confirms that a classical "hard corona-soft corona" paradigm is not valid for all types of nanoparticles and each system has a unique protein corona that is determined by the nature of the NP material.