State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P. R. China.
J Mater Chem B. 2020 Aug 12;8(31):6845-6856. doi: 10.1039/d0tb00499e.
Polyethylene glycol functionalization is believed to have the capacity of endowing nanomaterials with stealth characteristics, which can diminish the arrest by macrophages and adverse immunological response. However, our previous study provided evidences that polyethylene glycol-functionalized graphene oxide (GOP) stimulated a strong immunological response to macrophages despite non-internalization in vitro, raising safety concerns and potential immunostimulation use of GOP. In light of this finding, we herein systematically study the in vivo immunological response upon the exposure to GOP via intraperitoneal injection. Taking cytokines production, cell types in the peritoneal fluid, biochemical index, hematology and histopathology as in vivo indicators, we demonstrate that GOP still remains the stealth-but-activating capacity on macrophages in a time and dose-dependent manner. Specifically, the immune response can be significantly elevated after a single high-dose injection, indicating that GOP can be a new candidate adjuvant for immunotherapy. For multiple low dose injections, the immune response is gentle, temporary, and tolerable, which manifests the biocompatibility of GOP in general drug delivery. The above results can thus provide guidance for safe and rational use of GOP for various biomedical applications.
聚乙二醇（PEG）功能化被认为具有赋予纳米材料隐身特性的能力，可减少巨噬细胞的捕获和不良免疫反应。然而，我们之前的研究提供了证据，表明尽管 PEG 功能化的氧化石墨烯（GO）在体外没有被内吞，但仍能刺激巨噬细胞产生强烈的免疫反应，这引发了对 GOP 的安全性和潜在免疫刺激用途的关注。有鉴于此，我们在此通过腹腔注射系统地研究了体内暴露于 GOP 时的免疫反应。我们以细胞因子产生、腹腔液中的细胞类型、生化指标、血液学和组织病理学作为体内指标，证明 GOP 仍然以时间和剂量依赖的方式对巨噬细胞保持隐身但激活的能力。具体而言，单次高剂量注射后免疫反应可显著升高，表明 GOP 可能成为免疫治疗的新佐剂候选物。对于多次低剂量注射，免疫反应温和、暂时且耐受，这表明 GOP 在一般药物输送中具有生物相容性。因此，上述结果可为 GOP 用于各种生物医学应用的安全和合理使用提供指导。
