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Oligomer nanoparticle release from polylactic acid plastics catalysed by gut enzymes triggers acute inflammation

Nature Nanotechnology volume 18, pages 403–411 (2023)Cite this article

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Abstract

The health risks of exposure to ‘eco-friendly’ biodegradable plastics of anthropogenic origin and their effects on the gastrointestinal tract are largely unknown. Here we demonstrate that the enzymatic hydrolysis of polylactic acid microplastics generated nanoplastic particles by competing for triglyceride-degrading lipase during gastrointestinal processes. Nanoparticle oligomers were formed by hydrophobically driven self-aggregation. In a mouse model, polylactic acid oligomers and their nanoparticles bioaccumulated in the liver, intestine and brain. Hydrolysed oligomers caused intestinal damage and acute inflammation. A large-scale pharmacophore model revealed that oligomers interacted with matrix metallopeptidase 12. Mechanistically, high binding affinity (Kd = 13.3 μmol l−1) of oligomers to the catalytic zinc-ion finger domain led to matrix metallopeptidase 12 inactivation, which might mediate the adverse bowel inflammatory effects after exposure to polylactic acid oligomers. Biodegradable plastics are considered to be a solution to address environmental plastic pollution. Thus, understanding the gastrointestinal fates and toxicities of bioplastics will provide insights into potential health risks.

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Fig. 1: Gastric lipases digests PLA MPs.
Fig. 2: Characterization of PLA nanoplastic formation.
Fig. 3: Biodistribution and histopathology of PLA nanoplastics/oligomers in vitro and in vivo.
Fig. 4: PLA oligomers inactivate MMP12.
Fig. 5: MMP12-inactivation-mediated intestinal inflammation induced by PLA oligomers.

Data availability

All data supporting the findings of this study are available within this article and its Supplementary Information. Source data are provided with this paper.

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Acknowledgements

This work was primarily supported by the National Key R&D Program (nos. 2022YFC3702600 and 2022YFC3702601), the Singapore Ministry of Education Academic Research Fund Tier 1 (04MNP000567C120), the Ministry of Science and Technology of China (2022YF3701101), Startup Grant of Fudan University (no. JIH 1829010Y), Education Department of Anhui Province for Excellent Young Scientist (2022AH030076) and Second Tibetan Plateau Scientific Expedition and Research program (2019QZKK0682). We also acknowledge Y. Deng from Jinan University and Y. Zhan from Nanjing University for professional discussion and H. Yang, Y. Hua and S. Li from Research Center for Eco-Environmental Sciences for help with the NTA experiment.

Author information

Authors and Affiliations

  1. Department of Environmental Science and Engineering, Fudan University, Shanghai, China

    Mengjing Wang, Changzhi Shi, Jianmin Chen & Mingliang Fang

  2. School of Civil and Environmental Engineering, Nanyang Technological University, Singapore, Singapore

    Mengjing Wang, Junjie Yang, Linran Jia & Mingliang Fang

  3. Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China

    Qianqian Li

  4. Department of Toxicology, School of Public Health; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China

    Jia Lv & Yichao Huang

  5. State Key Laboratory of Proteomics, National Center for Protein Sciences–Beijing, Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, China

    Youdong Xu

  6. School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore

    Shae Linn Chua

  7. Sunlipo Biotech Research Center for Nanomedicine, Shanghai, China

    Huaiwen Chen

  8. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China

    Qian Liu

  9. School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, Singapore

    Changjin Huang

  10. Institute of Eco-Chongming, Shanghai, China

    Mingliang Fang

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  1. Mengjing Wang
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Contributions

M.W. and M.F. conceived and designed the study. Y.H., J.C. and M.F. supervised the study. M.W., Q.L. and J.L. performed the in vivo experiments and data analysis. C.S. and J.Y. conducted the mass spectrometry experiments. M.W. and Y.X. performed the MD simulations. M.W., Q.L., L.J. and Q.L. contributed to the biochemistry and characterization experiments. H.C. contributed to the synthesis experiments. S.L.C. and C.H. performed HepG2 cellular uptake experiments. M.W., Y.H., J.C. and M.F. wrote the manuscript with input from all the authors. All the authors discussed the results.

Corresponding authors

Correspondence to Yichao Huang, Jianmin Chen or Mingliang Fang.

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Nature Nanotechnology thanks Mathilde Body-Malapel and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Wang, M., Li, Q., Shi, C. et al. Oligomer nanoparticle release from polylactic acid plastics catalysed by gut enzymes triggers acute inflammation. Nat. Nanotechnol. 18, 403–411 (2023). https://doi.org/10.1038/s41565-023-01329-y

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