Lung Toxicity and Molecular Mechanisms of Lead-Based Perovskite Nanoparticles in the Respiratory System.

Lead-based perovskite nanoparticles (Pb-PNPs) have found extensive applications across diverse fields. However, because of poor stability and relatively strong water solubility, the potential toxicity of Pb-PNPs released into the environment during their manufacture, usage, and disposal has attracted significant attention. Inhalation is a primary route through which human exposure to Pb-PNPs occurs. Herein, the toxic effects and underlying molecular mechanisms of Pb-PNPs in the respiratory system are investigated. The in vitro cytotoxicity of CsPbBr3 nanoparticles in BEAS-2B cells is studied using multiple bioassays and electron microscopy. CsPbBr3 nanoparticles of different concentrations induce excessive oxidative stress and cell apoptosis. Furthermore, CsPbBr3 nanoparticles specifically recruit the TGF-β1, which subsequently induces epithelial-mesenchymal transition. In addition, the biodistribution and lung toxicity of representative CsPbBr3 nanoparticles in ICR mice are investigated following intranasal administration. These findings indicate that CsPbBr3 nanoparticles significantly induce pulmonary inflammation and epithelial-mesenchymal transition and can even lead to pulmonary fibrosis in mouse models. Above findings expose the adverse effects and molecular mechanisms of Pb-PNPs in the lung, which broadens the safety data of Pb-PNPs.

[1]  Xiaotang Fan,et al.  Neurotoxicity study of lead-based perovskite nanoparticles , 2023, Nano Today.

[2]  Zhanjun Gu,et al.  CsPbBr3 Perovskite Nanoparticles causes Colitis-Like Symptom via Promoting Intestinal Barrier Damage and Gut Microbiota Dysbiosis. , 2023, Small.

[3]  Li Cheng,et al.  Toxicity, Leakage, and Recycling of Lead in Perovskite Photovoltaics , 2023, Advanced Energy Materials.

[4]  A. Jen,et al.  Advances and challenges in understanding the microscopic structure–property–performance relationship in perovskite solar cells , 2022, Nature Energy.

[5]  Z. Cai,et al.  Metabolomics Reveal Nanoplastic-Induced Mitochondrial Damage in Human Liver and Lung Cells , 2022, Environmental science & technology.

[6]  G. Grancini,et al.  Rising of halide perovskite epitaxial structures , 2022, Nature Materials.

[7]  M. Reese,et al.  Building perovskite solar cells that last , 2022, Science.

[8]  Xiaochen Wu,et al.  Ultrathin, Transparent, and High Density Perovskite Scintillator Film for High Resolution X‐Ray Microscopic Imaging , 2022, Advanced science.

[9]  Alexander S. Timin,et al.  Incorporation of Perovskite Nanocrystals into Polymer Matrix for Enhanced Stability in Biological Media: In Vitro and In Vivo Studies. , 2022, ACS applied bio materials.

[10]  Yang Yang,et al.  Rethinking the A cation in halide perovskites , 2022, Science.

[11]  Myung‐Gil Kim,et al.  High-performance inorganic metal halide perovskite transistors , 2022, Nature Electronics.

[12]  Douglas H. Fabini,et al.  Diverging Expressions of Anharmonicity in Halide Perovskites , 2022, Advanced materials.

[13]  Irene Cantone,et al.  Environmental lead exposure from halide perovskites in solar cells. , 2022, Trends in ecology & evolution.

[14]  C. Bracken,et al.  The many regulators of epithelial−mesenchymal transition , 2021, Nature Reviews Molecular Cell Biology.

[15]  Quanbin Zhang,et al.  Low molecular weight fucoidan attenuating pulmonary fibrosis by relieving inflammatory reaction and progression of epithelial-mesenchymal transition. , 2021, Carbohydrate polymers.

[16]  Yue Zhang,et al.  MMP-3 activation is involved in copper oxide nanoparticle-induced epithelial-mesenchymal transition in human lung epithelial cells , 2021, Nanotoxicology.

[17]  S. Ryter,et al.  Pathogenic Mechanisms Underlying Idiopathic Pulmonary Fibrosis. , 2021, Annual review of pathology.

[18]  Chunfeng Zhang,et al.  Universal Existence of Localized Single‐Photon Emitters in the Perovskite Film of All‐Inorganic CsPbBr3 Microcrystals , 2021, Advanced materials.

[19]  Alexander S. Timin,et al.  Halide Perovskite Nanocrystals with Enhanced Water Stability for Upconversion Imaging in a Living Cell. , 2021, The journal of physical chemistry letters.

[20]  Xiaomin Liu,et al.  Highly Stable Inorganic Lead Halide Perovskite toward Efficient Photovoltaics. , 2021, Accounts of chemical research.

[21]  Jiani Xie,et al.  Eco-Friendly and Scalable Synthesis of Fullerenols with High Free Radical Scavenging Ability for Skin Radioprotection. , 2021, Small.

[22]  Jun Pan,et al.  Oriented Halide Perovskite Nanostructures and Thin Films for Optoelectronics. , 2021, Chemical reviews.

[23]  Jr-hau He,et al.  Halide Perovskites: A New Era of Solution‐Processed Electronics , 2021, Advanced materials.

[24]  R. Derynck,et al.  Epithelial plasticity, epithelial-mesenchymal transition, and the TGF-β family. , 2021, Developmental cell.

[25]  M. Johnston,et al.  Crystallization of CsPbBr3 single crystals in water for X-ray detection , 2021, Nature Communications.

[26]  A. Cantoral,et al.  Association between cumulative childhood blood lead exposure and hepatic steatosis in young Mexican adults. , 2021, Environmental research.

[27]  Yuliang Zhao,et al.  Reactive Oxygen Species‐Regulating Strategies Based on Nanomaterials for Disease Treatment , 2020, Advanced science.

[28]  M. Ahamed,et al.  Single-Walled Carbon Nanotubes Attenuate Cytotoxic and Oxidative Stress Response of Pb in Human Lung Epithelial (A549) Cells , 2020, International journal of environmental research and public health.

[29]  R. Reis,et al.  Adaptive epigenetic response of glutathione (GSH)-related genes against lead (Pb)-induced toxicity, in individuals chronically exposed to the metal. , 2020, Chemosphere.

[30]  J. Lam,et al.  Pulmonary Delivery of Biological Drugs , 2020, Pharmaceutics.

[31]  U. Vogel,et al.  Prediction of Chronic Inflammation for Inhaled Particles: the Impact of Material Cycling and Quarantining in the Lung Epithelium , 2020, Advanced materials.

[32]  Jianmin Su,et al.  Lead exposure activates the Nrf2/Keap1 pathway, aggravates oxidative stress, and induces reproductive damage in female mice. , 2020, Ecotoxicology and environmental safety.

[33]  Yueyue Shi,et al.  Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells , 2020, Frontiers in Pharmacology.

[34]  M. Davies Addressing the Stability of Lead Halide Perovskites , 2020, Joule.

[35]  Yuliang Zhao,et al.  Clinically Approved Carbon Nanoparticles with Oral Administration for Intestinal Radioprotection via Protecting the Small Intestinal Crypt Stem Cells and Maintaining the Balance of Intestinal Flora. , 2020, Small.

[36]  Irene Cantone,et al.  Biological impact of lead from halide perovskites reveals the risk of introducing a safe threshold , 2020, Nature Communications.

[37]  Haifeng Sun,et al.  Nanodrugs: Supramolecular Protein Nanodrugs with Coordination‐ and Heating‐Enhanced Photothermal Effects for Antitumor Therapy (Small 52/2019) , 2019 .

[38]  Shirong Zhang,et al.  An across-species comparison of the sensitivity of different organisms to Pb-based perovskites used in solar cells. , 2019, The Science of the total environment.

[39]  K. Tian,et al.  Sirtuin 6 inhibits MWCNTs-induced epithelial-mesenchymal transition in human bronchial epithelial cells via inactivating TGF-β1/Smad2 signaling pathway. , 2019, Toxicology and applied pharmacology.

[40]  S. Jimenez,et al.  Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases. , 2019, Physiological reviews.

[41]  Ayan A. Zhumekenov,et al.  All-inorganic perovskite nanocrystal scintillators , 2018, Nature.

[42]  Qiao Zhang,et al.  One-Pot Synthesis of Highly Stable CsPbBr3@SiO2 Core-Shell Nanoparticles. , 2018, ACS nano.

[43]  A. Hampl,et al.  Impact of acute and subchronic inhalation exposure to PbO nanoparticles on mice , 2018, Nanotoxicology.

[44]  I. Yu,et al.  Long-term exposures to low doses of silver nanoparticles enhanced in vitro malignant cell transformation in non-tumorigenic BEAS-2B cells. , 2016, Toxicology in vitro : an international journal published in association with BIBRA.

[45]  E. Birkner,et al.  Glutathione, glutathione-related enzymes, and oxidative stress in individuals with subacute occupational exposure to lead. , 2016, Environmental toxicology and pharmacology.

[46]  Henry J Snaith,et al.  Metal-halide perovskites for photovoltaic and light-emitting devices. , 2015, Nature nanotechnology.

[47]  O. Eickelberg,et al.  Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype , 2014, European Respiratory Review.

[48]  N. Zawia,et al.  Infantile exposure to lead and late-age cognitive decline: Relevance to AD , 2014, Alzheimer's & Dementia.

[49]  Samy Lamouille,et al.  Molecular mechanisms of epithelial–mesenchymal transition , 2014, Nature Reviews Molecular Cell Biology.

[50]  Marianne Geiser,et al.  Deposition and biokinetics of inhaled nanoparticles , 2010, Particle and Fibre Toxicology.

[51]  Tsutomu Miyasaka,et al.  Organometal halide perovskites as visible-light sensitizers for photovoltaic cells. , 2009, Journal of the American Chemical Society.

[52]  M. Bailey,et al.  Updating the ICRP human respiratory tract model. , 2007, Radiation protection dosimetry.

[53]  A. Ledbetter,et al.  Systemic translocation of particulate matter-associated metals following a single intratracheal instillation in rats. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[54]  L. Mortelmans,et al.  Passage of Inhaled Particles Into the Blood Circulation in Humans , 2002, Circulation.

[55]  H. Wichmann,et al.  The effect of low-level blood lead on hematologic parameters in children. , 2000, Environmental research.

[56]  J. Xie,et al.  Fullerenol@nano-montmorillonite nanocomposite as an efficient radioprotective agent for ameliorating radioactive duodenal injury , 2022 .

[57]  Qiangzhen Yang,et al.  Lead-mediated inhibition of lysine acetylation and succinylation causes reproductive injury of the mouse testis during development. , 2019, Toxicology letters.