CYP450 activation and mitophagy induction mediate Ti3C2 MXene detoxification in RAW 264.7 cells
Yujiao Liu1, Xuan Mao2, Yongyi Wei2
1Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Institute of Environmental Research at the Greater Bay Area, Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Guangzhou University, Guangzhou 510006, China.
Macrophages use a dual defense strategy to detoxify MXenes, two-dimensional nanomaterials. Accelerated oxidation and mitophagy process these materials, revealing new pathways for designing safer nanomaterials.
Area of Science:
- Nanotechnology and Materials Science
- Cellular Biology and Toxicology
Background:
- Engineered nanoparticles, including MXenes, present environmental and health concerns.
- Traditional toxicology often neglects cellular defense mechanisms against nanoparticles.
- MXenes are 2D materials with conductivity and biocompatibility but prone to oxidation.
Purpose of the Study:
- To elucidate macrophage detoxification strategies for MXenes.
- To investigate the role of oxidative degradation in MXene processing.
- To explore the cellular defense mechanisms activated by MXene exposure.
Main Methods:
- Utilized RAW 264.7 macrophage cell line.
- Investigated intracellular oxidation of Ti3C2 MXene.
- Analyzed the roles of CYP450 enzymes, reactive oxygen species, and mitophagy (PINK1/Parkin-dependent).
Main Results:
- Ti3C2 MXene undergoes accelerated intracellular oxidation, facilitating detoxification.
- MXene-induced activation of CYP450 and ROS generation metabolize MXene into less toxic oxidized forms.
- Oxidative damage triggers PINK1/Parkin-dependent mitophagy to remove damaged organelles.
Conclusions:
- Macrophage detoxification of MXenes involves a bipartite mechanism: oxidation and mitophagy.
- MXene oxidation is a critical detoxification trigger, not merely a material limitation.
- Findings offer a new paradigm for designing safer 2D nanomaterials, with future research on long-term effects needed.
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