Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors

Abstract Background Malignant tumor is usually associated with epigenetic dysregulation, such as overexpression of histone deacetylase (HDAC), thus HDAC has emerged as a therapeutic target for cancer. Histone deacetylase inhibitor has been approved for clinical use to treat hematological cancers. Ho...

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Autores principales:	Huan Li, Songpei Li, Yinshan Lin, Sheng Chen, Langyu Yang, Xin Huang, Hao Wang, Xiyong Yu, Lingmin Zhang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Artificial exosomes Upconversion nanoparticles Epigenetic inhibition M1 macrophages Spatiotemporal-resolved delivery Biotechnology TP248.13-248.65 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/1046fadceb8a4fc7ab61b69c4b80c7ce
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spelling	oai:doaj.org-article:1046fadceb8a4fc7ab61b69c4b80c7ce2021-11-21T12:29:36ZArtificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors10.1186/s12951-021-01107-91477-3155https://doaj.org/article/1046fadceb8a4fc7ab61b69c4b80c7ce2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01107-9https://doaj.org/toc/1477-3155Abstract Background Malignant tumor is usually associated with epigenetic dysregulation, such as overexpression of histone deacetylase (HDAC), thus HDAC has emerged as a therapeutic target for cancer. Histone deacetylase inhibitor has been approved for clinical use to treat hematological cancers. However, the low solubility, short circulation lifetime, and high cytotoxicity partially limited their applications in solid tumor. Methods The upconversion nanoparticles (UC) modified with mesoporous silica (SUC) was used to load an HDACI, suberoylanilide hydroxamic acid (SAHA), and further camouflaged with M1 macrophage-derived exosome membranes (EMS). EMS was characterized in size and compositions. We also analyzed the epigenetic regulation induced by EMS. Furthermore, we evaluate the biodistribution and in vivo tumor inhibition after the systemic administration of EMS. Results This novel style spatiotemporal-resolved drug delivery system, EMS showed a high loading efficiency of SAHA. EMS could be taken up by lung cancer cells and lead to efficient epigenetic inhibition. We found that the integrin α4β1 on M1-EM, was crucial for the homing of EMS to tumor tissues for the first time. In tumor-bearing mice, EMS showed spatiotemporal-resolved properties and facilitated the drug accumulation in the tumors, which induced superior anti-tumor effects. Conclusion This novel style of spatiotemporal-resolved nanoparticles can be used as a theranostic platform for lung cancer therapy. Graphical AbstractHuan LiSongpei LiYinshan LinSheng ChenLangyu YangXin HuangHao WangXiyong YuLingmin ZhangBMCarticleArtificial exosomesUpconversion nanoparticlesEpigenetic inhibitionM1 macrophagesSpatiotemporal-resolved deliveryBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Artificial exosomes Upconversion nanoparticles Epigenetic inhibition M1 macrophages Spatiotemporal-resolved delivery Biotechnology TP248.13-248.65 Medical technology R855-855.5
spellingShingle	Artificial exosomes Upconversion nanoparticles Epigenetic inhibition M1 macrophages Spatiotemporal-resolved delivery Biotechnology TP248.13-248.65 Medical technology R855-855.5 Huan Li Songpei Li Yinshan Lin Sheng Chen Langyu Yang Xin Huang Hao Wang Xiyong Yu Lingmin Zhang Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors
description	Abstract Background Malignant tumor is usually associated with epigenetic dysregulation, such as overexpression of histone deacetylase (HDAC), thus HDAC has emerged as a therapeutic target for cancer. Histone deacetylase inhibitor has been approved for clinical use to treat hematological cancers. However, the low solubility, short circulation lifetime, and high cytotoxicity partially limited their applications in solid tumor. Methods The upconversion nanoparticles (UC) modified with mesoporous silica (SUC) was used to load an HDACI, suberoylanilide hydroxamic acid (SAHA), and further camouflaged with M1 macrophage-derived exosome membranes (EMS). EMS was characterized in size and compositions. We also analyzed the epigenetic regulation induced by EMS. Furthermore, we evaluate the biodistribution and in vivo tumor inhibition after the systemic administration of EMS. Results This novel style spatiotemporal-resolved drug delivery system, EMS showed a high loading efficiency of SAHA. EMS could be taken up by lung cancer cells and lead to efficient epigenetic inhibition. We found that the integrin α4β1 on M1-EM, was crucial for the homing of EMS to tumor tissues for the first time. In tumor-bearing mice, EMS showed spatiotemporal-resolved properties and facilitated the drug accumulation in the tumors, which induced superior anti-tumor effects. Conclusion This novel style of spatiotemporal-resolved nanoparticles can be used as a theranostic platform for lung cancer therapy. Graphical Abstract
format	article
author	Huan Li Songpei Li Yinshan Lin Sheng Chen Langyu Yang Xin Huang Hao Wang Xiyong Yu Lingmin Zhang
author_facet	Huan Li Songpei Li Yinshan Lin Sheng Chen Langyu Yang Xin Huang Hao Wang Xiyong Yu Lingmin Zhang
author_sort	Huan Li
title	Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors
title_short	Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors
title_full	Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors
title_fullStr	Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors
title_full_unstemmed	Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors
title_sort	artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1046fadceb8a4fc7ab61b69c4b80c7ce
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_version_	1718418927833317376

Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors

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