胃肠道是口服纳米颗粒(NPs)的主要靶点，同时受到细菌成分等有害物质的影响。我们研究了当从巨噬细胞生长序列J774A.1和已分化的Caco-2肠上皮细胞与59纳米二氧化硅(SiO2) NPs在霍乱毒素亚单位B (CTxB)存在下接触时的相互作用。CTxB能够通过结合在两种细胞系表达的单碱基神经节苷脂(GM1)受体来影响细胞功能并调节内吞作用。在将巨噬细胞与CTxB刺激后，我们观察到了膜结构的显著变化，但在Caco-2细胞中没有观察到，也未检测到促炎因子肿瘤坏死因子-α (TNF-α)的分泌。然后，将细胞暴露于59纳米SiO2 NPs和CtxB依序和同时，导致J774A.1细胞中高度的NP摄取，但未检测到Caco-2细胞中的摄取。流式细胞仪分析结果显示，J774A.1细胞暴露于CTxB后，SiO2 NPs的摄取显着减少。相反，高度选择性的Caco-2细胞在CTxB暴露后对NPs的摄取不受影响。基于共定位研究，CTxB和NPs可能通过共享的内吞途径进入细胞，然后分选至不同的细胞内室。我们的研究结果对CTxB在吞噬细胞中但不在分化的肠道细胞中调节SiO2 NP摄取的功能提供了新的见解。

The gastrointestinal tract is the main target of orally ingested nanoparticles (NPs) and at the same time is exposed to noxious substances, such as bacterial components. We investigated the interaction of 59 nm silica (SiO2) NPs with differentiated Caco-2 intestinal epithelial cells in the presence of cholera toxin subunit B (CTxB) and compared the effects to J774A.1 macrophages. CTxB can affect cellular functions and modulate endocytosis via binding to the monosialoganglioside (GM1) receptor, expressed on both cell lines. After stimulating macrophages with CTxB, we observed notable changes in the membrane structure but not in Caco-2 cells, and no secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) was detected. Cells were then exposed to 59 nm SiO2 NPs and CtxB sequentially and simultaneously, resulting in a high NP uptake in J774A.1 cells, but no uptake in Caco-2 cells was detected. Flow cytometry analysis revealed that the exposure of J774A.1 cells to CTxB resulted in a significant reduction in the uptake of SiO2 NPs. In contrast, the uptake of NPs by highly selective Caco-2 cells remained unaffected following CTxB exposure. Based on colocalization studies, CTxB and NPs might enter cells via shared endocytic pathways, followed by their sorting into different intracellular compartments. Our findings provide new insights into CTxB's function of modulating SiO2 NP uptake in phagocytic but not in differentiated intestine cells.