Hayakawa Natsuki, Kitayama Yukiya, Igarashi Kazunori, Matsumoto Yu, Takano Eri, Sunayama Hirobumi, Takeuchi Toshifumi
Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
ACS Appl Mater Interfaces. 2022 Apr 13;14(14):16074-16081. doi: 10.1021/acsami.2c01953. Epub 2022 Mar 30.
Regulation of nanomaterial-cell interaction is an important requisite for a variety of biomedical applications such as drug delivery systems and theranostics. Here, we demonstrate the regulation of nanomaterial-cell interaction using the oriented adsorption of intrinsic immunoglobulin G (IgG) on molecularly imprinted polymer nanogels (MIP-NGs) capable of recognizing the fragment crystallizable (Fc) domain of IgG. The unique domain recognition property resulted in the suppression of the immune response in Fc domain receptor-possessing macrophages and natural killer cells due to the regulation of protein corona based on the oriented adsorption of IgG. This resulted in the hindrance of the Fc domain, which is the trigger of an immune response. Furthermore, the acquisition of stealth capability was successfully demonstrated in vivo using intravital confocal laser scanning microscopy. The domain imprinting proposed in this study will provide a new strategy for creating nanomaterials capable of domain recognition-based oriented adsorption of intrinsic proteins in situ, thus regulating the protein corona formed on the nanomaterials. Thus, the unique Fc domain-recognition nanomaterial developed in our study can be used for various biomedical applications to target specific cells without triggering an immune response.
纳米材料与细胞相互作用的调控是药物递送系统和诊疗一体化等多种生物医学应用的重要前提条件。在此,我们展示了利用固有免疫球蛋白G(IgG)在能够识别IgG可结晶片段(Fc)结构域的分子印迹聚合物纳米凝胶(MIP-NGs)上的定向吸附来调控纳米材料与细胞的相互作用。这种独特的结构域识别特性由于基于IgG的定向吸附对蛋白质冠层的调控,导致具有Fc结构域受体的巨噬细胞和自然杀伤细胞中的免疫反应受到抑制。这导致了作为免疫反应触发因素的Fc结构域受到阻碍。此外,使用活体共聚焦激光扫描显微镜在体内成功证明了隐形能力的获得。本研究中提出的结构域印迹将为创建能够原位基于结构域识别对固有蛋白质进行定向吸附的纳米材料提供一种新策略,从而调控在纳米材料上形成的蛋白质冠层。因此,我们研究中开发的独特的Fc结构域识别纳米材料可用于各种生物医学应用,以靶向特定细胞而不引发免疫反应。