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Denatured corona proteins mediate the intracellular bioactivities of nanoparticles via the unfolded protein response
Liu,Shang1; Wang,Zhenzhen1,2; Jiang,Xinbang1; Gan,Jingjing1; Tian,Xuejiao1; Xing,Zhen1; Yan,Yiqing1; Chen,Jiahui1; Zhang,Junfeng1; Wang,Chunming2; Dong,Lei1,3
2021
Source PublicationBiomaterials
ISSN0142-9612
Volume265
AbstractBiomolecular corona formed on nanoparticles (NPs) influences the latter's in vivo biological effects. Nanomaterials with different physicochemical properties exert similar adverse effects, such as cytotoxicity, suggesting the existence of ubiquitous signals during various corona formations that mediate common and fundamental cellular events. Here, we discover the involvement of the unfolded protein response (UPR) and recruited chaperones in the corona. Specially, heat shock protein 90 kDa α class B member 1 (Hsp90ab1) is abundantly enriched in the corona, accompanied by substantial aggregation of misfolded protein on particles intracellularly. Further analysis reveals the particulate matter 2.5 (PM2.5) and metal-containing particles are more capable of denaturing proteins. The recruited Hsp90ab1 activates diverse NPs' pathological behaviour by heat stress response (HSR), which were significantly reversed by geldanamycin (GA), the inhibitor of Hsp90ab1. Murine lung inflammation induced by PM2.5 and iron oxide NPs (FeONPs) is suppressed by GA, highlighting that Hsp90ab1-mediated UPR is a potential target for the treatment of environmental pollution-related illnesses. Based on our findings, the UPR and Hsp90ab1 presented in the corona of particles initiate fundamental intracellular reactions that lead to common pathological outcomes, which may provide new insights for understanding nanotoxicity and designing therapeutic approaches for diseases associated with environmental pollution.
KeywordCellular response Corona Hsp90ab1 Nanoparticles UPR
DOI10.1016/j.biomaterials.2020.120452
URLView the original
Language英语
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorDong,Lei
Affiliation1.State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences and Medical School,Nanjing University,Nanjing,163 Xianlin Avenue,210093,China
2.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Taipa,999078,China
3.Chemistry and Biomedicine Innovative Center,Nanjing University,Nanjing,163 Xianlin Avenue,210093,China
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GB/T 7714
Liu,Shang,Wang,Zhenzhen,Jiang,Xinbang,et al. Denatured corona proteins mediate the intracellular bioactivities of nanoparticles via the unfolded protein response[J]. Biomaterials,2021,265.
APA Liu,Shang,Wang,Zhenzhen,Jiang,Xinbang,Gan,Jingjing,Tian,Xuejiao,Xing,Zhen,Yan,Yiqing,Chen,Jiahui,Zhang,Junfeng,Wang,Chunming,&Dong,Lei.(2021).Denatured corona proteins mediate the intracellular bioactivities of nanoparticles via the unfolded protein response.Biomaterials,265.
MLA Liu,Shang,et al."Denatured corona proteins mediate the intracellular bioactivities of nanoparticles via the unfolded protein response".Biomaterials 265(2021).
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