Nanoparticles can act as transporters for synthetic molecules and biomolecules into cells, also in immunology. Antigen-presenting cells like dendritic cells are important targets for immunotherapy in nanomedicine. Therefore, we have used primary murine bone marrow-derived phagocytosing cells (bmPCs), i.e. dendritic cells and macrophages, to study their interaction with spherical barium sulphate particles of different size (40 nm, 420 nm, and 1 µm) and to follow their uptake pathway. Barium sulphate is chemically and biologically inert (no dissolution, no catalytic effects), i.e. we can separate the particle uptake effect from potential biological reactions. The colloidal stabilization of the nanoparticles was achieved by a layer of carboxymethylcellulose (CMC) which is biologically inert and gives the particles a negative zeta potential (i.e. charge). The particles were made fluorescent by conjugating 6-aminofluoresceine to CMC. Their uptake was visualized by flow cytometry, confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and correlative light and electron microscopy (CLEM). Barium sulphate particles of all sizes were readily taken up by dendritic cells and even more by macrophages, with the uptake increasing with time and particle concentration. They were mainly localized inside phagosomes, heterophagosomes, and in the case of nanoparticles also in the nearby cytosol. No particles were found in the nucleus. In nanomedicine, inorganic nanoparticles from the nanometer to the micrometer size are therefore well suited as transporters of biomolecules, including antigens, into dendritic cells and macrophages. The presented model system may also serve to describe the aseptic loosening of endoprostheses caused by abrasive wear of inert particles and the subsequent cell reaction, a question which relates to the field of nanotoxicology.

Statement of significance

The interaction of particles and cells is at the heart of nanomedicine and nanotoxicology, including abrasive wear from endoprostheses. It also comprises the immunological reaction to different kinds of nanomaterials, triggered by an immune response, e.g. by antigen-presenting cells. However, it is often difficult to separate the particle effect from a chemical or biochemical reaction to particles or their cargo. We show how chemically inert barium sulphate particles with three different sizes (nano, sub-micro, and micro) interact with relevant immune cells (primary dendritic cells and macrophages). Particles of all three sizes are readily taken up into both cell types by phagocytosis, but the uptake by macrophages is significantly more prominent than that by dendritic cells. The cells take up particles until they are virtually stuffed, but without direct adverse effect. The uptake increases with time and particle concentration. Thus, we have an ideal model system to follow particles into and inside cells without the side effect of a chemical particle effect, e.g. by degradation or ion release.

纳米颗粒还可以用作免疫分子中合成分子和生物分子进入细胞的转运蛋白。诸如树突状细胞之类的抗原呈递细胞是纳米医学中免疫治疗的重要靶标。因此，我们已使用鼠源性原代骨髓吞噬细胞（bmPC），即树突状细胞和巨噬细胞，研究它们与球形球形硫酸钡颗粒（大小分别为40 nm，420 nm和1 µm）的相互作用，并对其进行追踪。摄取途径。硫酸钡是化学和生物惰性的（无溶解，无催化作用），即我们可以将颗粒的吸收效应与潜在的生物反应区分开。纳米颗粒的胶体稳定作用是通过一层羧甲基纤维素（CMC）来实现的，该层具有生物学惰性，并赋予该颗粒负的Zeta电位（即收费）。通过使6-氨基荧光素与CMC缀合使颗粒发荧光。通过流式细胞术，共聚焦激光扫描显微镜（CLSM），扫描电子显微镜（SEM），透射电子显微镜（TEM）和相关光电子显微镜（CLEM）可视化它们的摄取。树突状细胞容易吸收各种尺寸的硫酸钡颗粒，巨噬细胞甚至会吸收更多，并且吸收量会随着时间和颗粒浓度的增加而增加。它们主要定位在吞噬体，异吞噬体内，就纳米颗粒而言，也位于附近的细胞质中。在细胞核中未发现任何颗粒。因此，在纳米医学中，从纳米级到微米级的无机纳米粒子非常适合作为生物分子（包括抗原）转运到树突状细胞和巨噬细胞中。

重要声明

颗粒与细胞的相互作用是纳米医学和纳米毒理学的核心，包括内部假体的磨损。它还包括由免疫反应（例如抗原呈递细胞）触发的针对不同种类纳米材料的免疫反应。但是，通常很难将颗粒效应与化学反应或生化反应与颗粒或它们的货物区分开。我们展示了具有三种不同大小（纳米，亚微米和微米）的化学惰性硫酸钡颗粒如何与相关的免疫细胞（原代树突状细胞和巨噬细胞）相互作用。通过吞噬作用，所有这三种大小的颗粒都很容易被两种细胞吸收，但是巨噬细胞的摄取比树突状细胞的摄取显着得多。细胞吸收颗粒直到被塞满为止，但没有直接的不良影响。吸收量随时间和颗粒浓度的增加而增加。因此，我们拥有一个理想的模型系统，可以跟踪粒子进入细胞内部和内部，而不会产生化学粒子效应（例如，降解或离子释放）的副作用。