Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro

• Main Authors: Gautam, Archana, Rakshit, Moumita, Nguyen, Kim Truc, Kathawala, Mustafa Hussain, Nguyen, Luong Thi Hien, Tay, Chor Yong, Wong, Esther, Ng, Kee Woei
• Other Authors: School of Materials Science & Engineering
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Biological sciences; Keratinocytes; Sunscreen
• Online Access: https://hdl.handle.net/10356/139366
• Institution: Nanyang Technological University

Engineered nanoparticles (NPs) such as TiO2 and ZnO are key UV-blocking ingredients in sunscreens. While toxicological risks of applying these materials are generally regarded as low due to minute levels of penetration across the skin, our understanding of the physiological influence of potential cell-nanoparticle interactions in the skin is limited. This study plugs the current knowledge gap by profiling TiO2 and ZnO NP interaction with primary human epidermal keratinocytes, based on potential levels of NP penetration across the skin. Specific attention was given to profiling real-life relevant levels of exposure, and accurate dosimetry measurements in vitro. ZnO was expectedly more cytotoxic than TiO2. Although both NPs generated Reactive Oxygen Species (ROS) and Mitochondrial Superoxide (MSO) within 4 h exposure to sub-lethal concentrations, ZnO induction of these oxidative stress markers increased much more significantly after 24 h exposure. Exposure to increasing NP concentrations increased autophagy induction along with activation of inflammatory responses in the keratinocytes, primarily through the TRAF6-mediated pathway. Sustained induction of autophagy led to degradation of TRAF6 and, only in the case of TiO2, reduced NF-κB activation. This pro-survival mode of autophagy induction provides further insights into the on-going debate on the use of these NPs in consumer products.