State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
University of Chinese Academy of Sciences, Beijing 100049, PR China.
Nat Commun. 2017 Feb 24;8:14537. doi: 10.1038/ncomms14537.
Engineered nanomaterials promise to transform medicine at the bio-nano interface. However, it is important to elucidate how synthetic nanomaterials interact with critical biological systems before such products can be safely utilized in humans. Past evidence suggests that polyethylene glycol-functionalized (PEGylated) nanomaterials are largely biocompatible and elicit less dramatic immune responses than their pristine counterparts. We here report results that contradict these findings. We find that PEGylated graphene oxide nanosheets (nGO-PEGs) stimulate potent cytokine responses in peritoneal macrophages, despite not being internalized. Atomistic molecular dynamics simulations support a mechanism by which nGO-PEGs preferentially adsorb onto and/or partially insert into cell membranes, thereby amplifying interactions with stimulatory surface receptors. Further experiments demonstrate that nGO-PEG indeed provokes cytokine secretion by enhancing integrin β-related signalling pathways. The present results inform that surface passivation does not always prevent immunological reactions to 2D nanomaterials but also suggest applications for PEGylated nanomaterials wherein immune stimulation is desired.
工程纳米材料有望在生物-纳米界面上改变医学。然而，在将这些产品安全地应用于人类之前，重要的是阐明合成纳米材料如何与关键的生物系统相互作用。过去的证据表明，聚乙二醇功能化（PEGylated）纳米材料在很大程度上是生物相容的，并且比其原始对应物引起的免疫反应不那么剧烈。我们在这里报告的结果与这些发现相矛盾。我们发现，尽管聚乙二醇化氧化石墨烯纳米片（nGO-PEGs）没有被内化，但仍能刺激腹腔巨噬细胞产生强烈的细胞因子反应。原子分子动力学模拟支持一种机制，即 nGO-PEG 优先吸附在细胞膜上和/或部分插入细胞膜，从而增强与刺激性表面受体的相互作用。进一步的实验表明，nGO-PEG 通过增强整合素 β 相关信号通路确实引发细胞因子的分泌。目前的结果表明，表面钝化并不总是能防止对 2D 纳米材料的免疫反应，也为需要免疫刺激的 PEG 化纳米材料的应用提供了信息。
