ESCRT III Regulates Lysosomal Perinuclear Clustering by Inhibiting Kinesin 1 Leading to Agnps Cytotoxicity in Human Cells
Abstract Silver nanoparticles (AgNPs) are recognized for their strong antibacterial properties, particularly in applications such as wound and burn treatment; however, the mechanisms of AgNP‐induced cytotoxicity remain inadequately defined. This study investigates the role of lysosomal dysfunction...
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| Language: | English |
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Wiley-VCH
2025-05-01
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| Series: | Advanced Materials Interfaces |
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| Online Access: | https://doi.org/10.1002/admi.202400944 |
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| author | Tiantian Liu Aiguo Xie Chao Xing RuiZhe He Wei Ni Yinbo Peng Peng Xu Yong Fang |
| author_facet | Tiantian Liu Aiguo Xie Chao Xing RuiZhe He Wei Ni Yinbo Peng Peng Xu Yong Fang |
| author_sort | Tiantian Liu |
| collection | DOAJ |
| description | Abstract Silver nanoparticles (AgNPs) are recognized for their strong antibacterial properties, particularly in applications such as wound and burn treatment; however, the mechanisms of AgNP‐induced cytotoxicity remain inadequately defined. This study investigates the role of lysosomal dysfunction in AgNP‐induced cytotoxicity, focusing on lysosomal perinuclear clustering (LPC) and its relationship with cellular apoptosis. Human fibroblast HS27 cells are treated with 24 µg mL−1 AgNPs over 48 h, and lysosomal dynamics, cellular localization, and apoptosis rates are analyzed through confocal microscopy and flow cytometry. Protein expression levels of charged multivesicular body protein 4B(CHMP4B) and Kinesin 1, which are central to lysosomal transport and membrane repair, are examined via western blotting. The findings reveal that AgNP exposure leads to LPC and an increase in apoptosis in a time‐dependent manner, accompanied by reduced Kinesin 1 expression. Further, inhibition of CHMP4B and Kinesin 1 significantly promoted apoptosis, while their overexpression mitigated AgNP‐induced cytotoxic effects, underscoring their essential roles in lysosomal integrity. This study provides new insights into the cellular pathways of AgNP‐induced cytotoxicity, focusing on lysosomal transport disruption, and suggests potential molecular targets to reduce adverse effects in therapeutic applications. These results lay a foundation for optimizing AgNP efficacy and improving their safety profile in clinical settings. |
| format | Article |
| id | doaj-art-88dce8545598425ca730fe9cf3eedec7 |
| institution | OA Journals |
| issn | 2196-7350 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Advanced Materials Interfaces |
| spelling | doaj-art-88dce8545598425ca730fe9cf3eedec72025-08-20T02:26:19ZengWiley-VCHAdvanced Materials Interfaces2196-73502025-05-011210n/an/a10.1002/admi.202400944ESCRT III Regulates Lysosomal Perinuclear Clustering by Inhibiting Kinesin 1 Leading to Agnps Cytotoxicity in Human CellsTiantian Liu0Aiguo Xie1Chao Xing2RuiZhe He3Wei Ni4Yinbo Peng5Peng Xu6Yong Fang7Department of Burns and Plastic Surgery Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201900 ChinaDepartment of Burns and Plastic Surgery Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201900 ChinaDepartment of Burns and Plastic Surgery Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201900 ChinaDepartment of Burns and Plastic Surgery Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201900 ChinaWuhan National Laboratory for Optoelectronics Hua Zhong University of Science and Technology 1037 Luoyu Road Wuhan Hubei 430000 ChinaDepartment of Burns and Plastic Surgery Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201900 ChinaDepartment of Burns and Plastic Surgery Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201900 ChinaDepartment of Burns and Plastic Surgery Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201900 ChinaAbstract Silver nanoparticles (AgNPs) are recognized for their strong antibacterial properties, particularly in applications such as wound and burn treatment; however, the mechanisms of AgNP‐induced cytotoxicity remain inadequately defined. This study investigates the role of lysosomal dysfunction in AgNP‐induced cytotoxicity, focusing on lysosomal perinuclear clustering (LPC) and its relationship with cellular apoptosis. Human fibroblast HS27 cells are treated with 24 µg mL−1 AgNPs over 48 h, and lysosomal dynamics, cellular localization, and apoptosis rates are analyzed through confocal microscopy and flow cytometry. Protein expression levels of charged multivesicular body protein 4B(CHMP4B) and Kinesin 1, which are central to lysosomal transport and membrane repair, are examined via western blotting. The findings reveal that AgNP exposure leads to LPC and an increase in apoptosis in a time‐dependent manner, accompanied by reduced Kinesin 1 expression. Further, inhibition of CHMP4B and Kinesin 1 significantly promoted apoptosis, while their overexpression mitigated AgNP‐induced cytotoxic effects, underscoring their essential roles in lysosomal integrity. This study provides new insights into the cellular pathways of AgNP‐induced cytotoxicity, focusing on lysosomal transport disruption, and suggests potential molecular targets to reduce adverse effects in therapeutic applications. These results lay a foundation for optimizing AgNP efficacy and improving their safety profile in clinical settings.https://doi.org/10.1002/admi.202400944AgNPsapoptosisESCRT IIIKinesin 1lysosomes |
| spellingShingle | Tiantian Liu Aiguo Xie Chao Xing RuiZhe He Wei Ni Yinbo Peng Peng Xu Yong Fang ESCRT III Regulates Lysosomal Perinuclear Clustering by Inhibiting Kinesin 1 Leading to Agnps Cytotoxicity in Human Cells Advanced Materials Interfaces AgNPs apoptosis ESCRT III Kinesin 1 lysosomes |
| title | ESCRT III Regulates Lysosomal Perinuclear Clustering by Inhibiting Kinesin 1 Leading to Agnps Cytotoxicity in Human Cells |
| title_full | ESCRT III Regulates Lysosomal Perinuclear Clustering by Inhibiting Kinesin 1 Leading to Agnps Cytotoxicity in Human Cells |
| title_fullStr | ESCRT III Regulates Lysosomal Perinuclear Clustering by Inhibiting Kinesin 1 Leading to Agnps Cytotoxicity in Human Cells |
| title_full_unstemmed | ESCRT III Regulates Lysosomal Perinuclear Clustering by Inhibiting Kinesin 1 Leading to Agnps Cytotoxicity in Human Cells |
| title_short | ESCRT III Regulates Lysosomal Perinuclear Clustering by Inhibiting Kinesin 1 Leading to Agnps Cytotoxicity in Human Cells |
| title_sort | escrt iii regulates lysosomal perinuclear clustering by inhibiting kinesin 1 leading to agnps cytotoxicity in human cells |
| topic | AgNPs apoptosis ESCRT III Kinesin 1 lysosomes |
| url | https://doi.org/10.1002/admi.202400944 |
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