Tay Chor Yong, Fang Wanru, Setyawati Magdiel Inggrid, Chia Sing Ling, Tan Kai Soo, Hong Catherine Hsu Ling, Leong David Tai
Department of Chemical and Biomolecular Engineering, National University of Singapore , 4 Engineering Drive 4, Singapore 117585, Singapore.
ACS Appl Mater Interfaces. 2014 May 14;6(9):6248-56. doi: 10.1021/am501266a. Epub 2014 Apr 29.
Nanomaterials (NMs) such as titanium dioxide (nano-TiO2) and hydroxyapatite (nano-HA) are widely used in food, personal care, and many household products. Due to their extensive usage, the risk of human exposure is increased and may trigger NMs specific biological outcomes as the NMs interface with the cells. However, the interaction of nano-TiO2 and nano-HA with cells, their uptake and subcellular distribution, and the cytotoxic effects are poorly understood. Herein, we characterized and examined the cellular internalization, inflammatory response and cytotoxic effects of nano-TiO2 and nano-HA using TR146 human oral buccal epithelial cells as an in vitro model. We showed both types of NMs were able to bind to the cellular membrane and passage into the cells in a dose dependent manner. Strikingly, both types of NMs exhibited distinct subcellular distribution profile with nano-HA displaying a higher preference to accumulate near the cell membrane compared to nano-TiO2. Exposure to both types of NMs caused an elevated reactive oxygen species (ROS) level and expression of inflammatory transcripts with increasing NMs concentration. Although cells treated with nano-HA induces minimal apoptosis, nano-TiO2 treated samples displayed approximately 28% early apoptosis after 24 h of NMs exposure. We further showed that nano-TiO2 mediated cell death is independent of the classical p53-Bax apoptosis pathway. Our findings provided insights into the potential cellular fates of human oral epithelial cells as they interface with industrial grade nano-HA and nano-TiO2.
纳米材料（NMs），如二氧化钛（纳米TiO₂）和羟基磷灰石（纳米HA），广泛应用于食品、个人护理和许多家用产品中。由于它们的广泛使用，人类接触的风险增加，并且当纳米材料与细胞相互作用时可能引发特定的生物学结果。然而，纳米TiO₂和纳米HA与细胞的相互作用、它们的摄取和亚细胞分布以及细胞毒性作用仍知之甚少。在此，我们以TR146人口腔颊黏膜上皮细胞作为体外模型，对纳米TiO₂和纳米HA的细胞内化、炎症反应和细胞毒性作用进行了表征和研究。我们发现这两种类型的纳米材料都能够与细胞膜结合并以剂量依赖的方式进入细胞。令人惊讶的是，两种类型的纳米材料都表现出不同的亚细胞分布特征，与纳米TiO₂相比，纳米HA更倾向于在细胞膜附近积累。暴露于这两种类型的纳米材料会导致活性氧（ROS）水平升高和炎症转录本的表达随着纳米材料浓度的增加而增加。虽然用纳米HA处理的细胞诱导的凋亡最少，但在暴露于纳米材料24小时后，用纳米TiO₂处理的样品显示出约28%的早期凋亡。我们进一步表明，纳米TiO₂介导的细胞死亡独立于经典的p53-Bax凋亡途径。我们的研究结果为人类口腔上皮细胞与工业级纳米HA和纳米TiO₂相互作用时的潜在细胞命运提供了见解。
