Department of Environmental Science, Institute for Biological and Environmental Sciences, Radboud University Nijmegen, 6500 GL, Nijmegen, The Netherlands.
Department of Toxicology, Radboud University Nijmegen, 6500 GL, Nijmegen, The Netherlands.
Sci Rep. 2022 Oct 24;12(1):17813. doi: 10.1038/s41598-022-20761-z.
Nanotechnology brings benefits in fields such as biomedicine but nanoparticles (NPs) may also have adverse health effects. The effects of surface-modified NPs at the cellular level have major implications for both medicine and toxicology. Semi-empirical and mechanism-based models aid to understand the cellular transport of various NPs and its implications for quantitatively biological exposure while avoiding large-scale experiments. We hypothesized relationships between NPs-cellular elimination, surface functionality and elimination pathways by cells. Surface free energy components were used to characterize the transport of NPs onto membranes and with lipid vesicles, covering both influences by size and hydrophobicity of NPs. The model was built based on properties of neutral NPs and cells, defining Van de Waals forces, electrostatic forces and Lewis acid-base (polar) interactions between NPs and vesicles as well as between vesicles and cell membranes. We yielded a generic model for estimating exocytosis rate constants of various neutral NPs by cells based on the vesicle-transported exocytosis pathways. Our results indicate that most models are well fitted (R ranging from 0.61 to 0.98) and may provide good predictions of exocytosis rate constants for NPs with differing surface functionalities (prediction errors are within 2 times for macrophages). Exocytosis rates differ between cancerous cells with metastatic potential and non-cancerous cells. Our model provides a reference for cellular elimination of NPs, and intends for medical applications and risk assessment.
纳米技术在生物医药等领域带来了益处，但纳米颗粒（NPs）也可能对健康产生不良影响。表面修饰的 NPs 在细胞水平上的影响对医学和毒理学都有重大意义。半经验和基于机制的模型有助于理解各种 NPs 的细胞转运及其对定量生物学暴露的影响，同时避免大规模实验。我们假设 NPs-细胞消除、表面功能和细胞消除途径之间存在关系。表面自由能成分用于描述 NPs 在细胞膜和脂质体上的传输，涵盖了 NPs 的大小和疏水性的影响。该模型基于中性 NPs 和细胞的特性构建，定义了 NPs 和脂质体之间以及脂质体和细胞膜之间的范德华力、静电力和路易斯酸碱（极性）相互作用。我们基于通过囊泡转运的胞吐途径，为各种中性 NPs 的细胞胞吐率常数生成了一个通用模型。我们的结果表明，大多数模型拟合良好（R 范围从 0.61 到 0.98），并且可以对具有不同表面功能的 NPs 的胞吐率常数进行很好的预测（对于巨噬细胞，预测误差在 2 倍以内）。具有转移潜力的癌细胞和非癌细胞之间的胞吐率不同。我们的模型为 NPs 的细胞消除提供了参考，旨在用于医学应用和风险评估。
