Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, P. R. China.
Department of gastroenterology, Shanghai Sixth People's Hospital, Shanghai JiaoTong University, P. R. China.
Nanoscale. 2019 Dec 21;11(47):22849-22859. doi: 10.1039/c9nr08261a. Epub 2019 Nov 22.
Inorganic nanoparticles (NPs), particularly iron oxide (IO) and gold (Au) NPs, are widely used in a variety of biomedical applications, such as diagnosis and cancer therapy. As an important component of host defense in organisms, macrophages play a crucial role in responding to foreign substances, such as nanoparticles. Thus, it is of utmost importance to understand the nanotoxicity effects on the immune system by investigating the influences of such nanoparticles. In this study, we found that macrophages can take up large amounts of amphiphilic polymer (PMA)-modified Au and IO NPs, which will induce macrophage cell vacuolization and enhance macrophage polarization. This mechanism is an essential part of the immune response in vivo. In addition, we report that smaller-sized nanoparticles (ca. 4 nm) show more significant effects on the macrophage polarization and caused lysosomal damage compared to larger nanoparticles (ca. 14 nm). Moreover, the amount of NP uptake in macrophages decreases upon trapping the PMA with PEG, resulting in reduced vacuolization and a reduced immune response. We hypothesize that vacuoles are formed in large amounts during NP uptake by macrophages, which enhances the immune response and induces macrophages toward M1 polarization. These findings are potentially useful for disease treatment and understanding the immune response when NPs are used in vitro and in vivo.
无机纳米粒子（NPs），特别是氧化铁（IO）和金（Au）NPs，广泛应用于各种生物医学应用，如诊断和癌症治疗。作为生物体中宿主防御的重要组成部分，巨噬细胞在应对异物（如纳米粒子）方面起着至关重要的作用。因此，了解纳米粒子对免疫系统的毒性作用，研究这些纳米粒子的影响，至关重要。在本研究中，我们发现巨噬细胞可以摄取大量两亲聚合物（PMA）修饰的 Au 和 IO NPs，这将诱导巨噬细胞空泡化并增强巨噬细胞极化。该机制是体内免疫反应的重要组成部分。此外，我们报告称，与较大的纳米粒子（约 14nm）相比，较小尺寸的纳米粒子（约 4nm）对巨噬细胞极化的影响更为显著，并导致溶酶体损伤。此外，用 PEG 捕获 PMA 会导致巨噬细胞中 NP 的摄取量减少，从而减少空泡化和免疫反应。我们假设，巨噬细胞摄取 NP 时会形成大量的空泡，这增强了免疫反应，并诱导巨噬细胞向 M1 极化。这些发现对于疾病治疗以及理解 NP 在体外和体内应用时的免疫反应具有潜在的应用价值。
