IUF - Leibniz Research Institute for Environmental Medicine, Heinrich-Heine-University Duesseldorf , Duesseldorf , Germany.
Nanotoxicology. 2019 Oct;13(8):1133-1148. doi: 10.1080/17435390.2019.1643048. Epub 2019 Aug 9.
Despite of the increasing application of silica nanoparticles and identification of oral exposure as a major entry portal, we lack understanding of nanosilica effects in the gut. Thus, we investigated biointeractions of nanosilica with single intestinal cells. The invertebrate nematode was chosen as model organism with a tractable intestine and realistic target organism of nanomaterials in the environment. We found that nanosilica impairs the intestinal uptake of oligopeptides. Downstream to absorption by the apical OPT-2/PEP-2 transporter dipeptides were trapped in aberrant vesicles that grow over time and reach diameters of ≥6 μm. The peptide vesicles do not correspond to known organelles such as gut granules and form independently of related gene products GLO-1 or GLO-3. Formation of aberrant peptide vesicles also occurred independently of insulin/IGF-I receptor (DAF-2) signaling and loss of function mutants showed specific vesicle patterns including distinct localization along the apical membrane of single intestinal cells. As malnutrition of exposed manifested in reduced growth and a petite phenotype similar to OPT-2/PEP-2 transporter deficient mutants, we conclude that nanosilica-induced peptide vesicles represent a new compartment of di- and tripeptide trapping which disrupts hydrolysis of nutrient peptides and metabolism.
尽管二氧化硅纳米粒子的应用日益增多，并且已经确定口服暴露是主要的进入途径，但我们对肠道中纳米二氧化硅的影响仍缺乏了解。因此，我们研究了纳米二氧化硅与单个肠细胞的生物相互作用。选择无脊椎线虫作为模型生物，因为其肠道具有可操作性，并且是环境中纳米材料的实际目标生物。我们发现，纳米二氧化硅会损害肠道对寡肽的吸收。在被顶端 OPT-2/PEP-2 转运体吸收后，二肽被捕获在异常的囊泡中，这些囊泡随着时间的推移而增大，直径达到≥6μm。这些肽囊泡与已知的细胞器（如肠道颗粒）不同，并且独立于相关基因产物 GLO-1 或 GLO-3 形成。异常肽囊泡的形成也独立于胰岛素/IGF-I 受体 (DAF-2) 信号，并且功能丧失突变体表现出特定的囊泡模式，包括沿单个肠细胞的顶端膜的独特定位。由于暴露的 表现出营养不良，生长减少和小体型表型类似于 OPT-2/PEP-2 转运体缺陷突变体，因此我们得出结论，纳米二氧化硅诱导的肽囊泡代表了二肽和三肽捕获的新隔室，破坏了营养肽的水解和代谢。
