New Evidence for the Mechanisms of Nanoplastics Amplifying Cadmium Cytotoxicity: Trojan Horse Effect, Inflammatory Response, and Calcium Imbalance.
Abstract: Nanoplastics (NPs) are emerging pollutants worldwide. Particularly worrisome is that although studies have reported that NPs can amplify the biotoxicity of environmental pollutants, the specific mechanism remains unclear. Here, we found that NPs, even without significant toxicity (cell survival: 99.11%), amplified the hepatocyte toxicity of Cd. Mechanistically, higher Cd uptake (Δ = 23.80%) combined with crucial intracellular desorption behavior of Cd loaded in NPs (desorption rate: 82.70%) were identified as prerequisites for NPs amplifying Cd cytotoxicity. As for toxigenic pathways, the inflammatory response and calcium (Ca) signaling pathway were identified as the primary molecular events leading to the amplification of Cd cytotoxicity. Further phenotypic monitoring revealed that NPs synergized with Cd to induce more severe pyroptosis and apoptosis by activating the inflammatory caspase-1-dependent and Ca-mitochondrial-caspase-3 pathways to a greater extent, respectively. This study reveals and proves for the first time the "Trojan horse" effects of NPs, thus elucidating the actual mechanisms by which NPs act as toxicity amplifiers of pollutants, providing significant insights into accurate risk assessment of NPs in composite pollution.
Publication Date: 2025-05-11 PubMed ID: 40350783DOI: 10.1021/acs.est.5c01254Google Scholar: Lookup
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Summary
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This research examines how nanoplastics, small pollutants, can amplify the harmful effects of environmental pollutants like cadmium on liver cells, even though the nanoplastics themselves don’t pose a significant threat, a concept referred to as the “Trojan horse” effect.
Overview of the Research
- The researchers studied how nanoplastics (NPs), minute particles of plastic that are emerging pollutants globally, can elevate the destructive properties of other pollutants like cadmium (Cd). The phenomenon where NPs, which themselves don’t pose a considerable threat, enhance the toxicity of other pollutants is referred to as the “Trojan horse” effect.
- Contrary to most studies that have documented the amplification of pollutant toxicity by NPs, this research delves into the specific mechanisms that allow this to occur. The study showed that NPs enhance cadmium’s hepatocyte (liver cell) toxicity.
Cadmium Uptake and Desorption Behaviour
- The researchers found that a higher intake of Cadmium, when paired with significant intracellular desorption of Cadmium loaded in nanoplastics, is the preliminary requirement for NPs to enhance Cadmium’s cytotoxicity.
- It was observed that nanoplastics increase Cadmium uptake by 23.80%, while the desorption rate of Cadmium bound in nanoplastics was 82.70%, thereby amplifying the cytotoxicity of Cadmium.
The Toxigenic Pathways
- The inflammatory response and calcium signaling pathway were identified as the principal molecular events that trigger the amplification of Cadmium’s cytotoxicity.
- This clearly signifies the part played by inflammatory responses and calcium signaling pathways in manipulating the toxicity levels of pollutants.
Further Findings
- In-depth monitoring of phenotypes disclosed that nanoplastics synergize with Cadmium to evoke serious pyroptosis (a form of cell death) and apoptosis (programmed cell death).
- This exacerbates cell death by activating the inflammatory caspase-1-dependent and calcium-mitochondria-caspase-3 pathways.
- These findings are crucial as they mark the first time “Trojan horse” effects of nanoplastics have been confirmed, thus shedding light on actual mechanisms empowering NPs as toxicity amplifiers of pollutants.
Significance of the Research
- This research offers important insights about the role of nanoplastics in amplifying the toxicity of pollutants; key knowledge needed for the accurate risk assessment of nanoplastics in composite pollution.
- The understanding gained from the study can help in creating strategies to diminish the harmful environmental and health effects of nanoplastics.
Cite This Article
APA
Li X, Hu S, Yu Z, He F, Zhao X, Liu R.
(2025).
New Evidence for the Mechanisms of Nanoplastics Amplifying Cadmium Cytotoxicity: Trojan Horse Effect, Inflammatory Response, and Calcium Imbalance.
Environ Sci Technol.
https://doi.org/10.1021/acs.est.5c01254 Publication
Researcher Affiliations
- School of Environmental Science and Engineering, China-America CRC for Environment & Health, Shandong University, 72# Jimo Binhai Road, Qingdao, Shandong 266237, China.
- School of Environmental Science and Engineering, China-America CRC for Environment & Health, Shandong University, 72# Jimo Binhai Road, Qingdao, Shandong 266237, China.
- School of Environmental Science and Engineering, China-America CRC for Environment & Health, Shandong University, 72# Jimo Binhai Road, Qingdao, Shandong 266237, China.
- School of Environmental Science and Engineering, China-America CRC for Environment & Health, Shandong University, 72# Jimo Binhai Road, Qingdao, Shandong 266237, China.
- School of Environmental Science and Engineering, China-America CRC for Environment & Health, Shandong University, 72# Jimo Binhai Road, Qingdao, Shandong 266237, China.
- School of Environmental Science and Engineering, China-America CRC for Environment & Health, Shandong University, 72# Jimo Binhai Road, Qingdao, Shandong 266237, China.
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