Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery

Safia Naz,1,* Mingyu Wang,1,* Yuning Han,1 Bin Hu,1 Liping Teng,2 Juan Zhou,1 Huijie Zhang,1 Jinghua Chen11Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China; 2Wuxi Scho...

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Autores principales:	Naz S, Wang M, Han Y, Hu B, Teng L, Zhou J, Zhang H, Chen J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Mesoporous silica nanoparticles drug delivery enzyme-responsive multistage-targeting，cancer therapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/88408b84325d4d08bef89d217d894edc
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spelling	oai:doaj.org-article:88408b84325d4d08bef89d217d894edc2021-12-02T03:57:26ZEnzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery1178-2013https://doaj.org/article/88408b84325d4d08bef89d217d894edc2019-04-01T00:00:00Zhttps://www.dovepress.com/enzyme-responsive-mesoporous-silica-nanoparticles-for-tumor-cells-and--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Safia Naz,1,* Mingyu Wang,1,* Yuning Han,1 Bin Hu,1 Liping Teng,2 Juan Zhou,1 Huijie Zhang,1 Jinghua Chen11Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China; 2Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China*These authors contributed equally to this workBackground: Drug delivery systems (DDS) capable of targeting both cell and organelle levels are highly desirable for effective cancer therapy. In this study, we developed a novel enzyme-responsive, multistage-targeted anticancer DDS based on mesoporous silica nanoparticles (MSNs), which possessed both CD44-targeting and mitochondrial-targeting properties.Materials and methods: Triphenylphosphine (TPP), a mitochondria-targeting compound, was grafted onto the surface of MSNs firstly. Then, Doxorubicin (Dox) was encapsulated into the pore of MSNs, followed by capping with tumor-targeting molecules hyaluronic acid (HA) through electrostatic interactions to form the final product consist of Dox loaded, TPP attached, HA capped mesoporous silica nanoparticles (MSN-DPH).Results: Our results suggested that MSN-DPH was preferentially taken up by cancer cells via CD44 receptor-mediated endocytosis. Moreover, MSN-DPH mainly accumulated in mitochondria owing to the mitochondrial-targeting ability of TPP. Degradation of HA by overexpressed HAase facilitated the release of Dox in cancer cells. Thus, MSN-DPH efficiently killed the cancer cells while exhibited much lower cytotoxicity to normal cells.Conclusion: This study demonstrates a promising multistage-targeted DDS for cancer chemotherapy.Keywords: mesoporous silica nanoparticles, drug delivery, enzyme-responsive, multistage-targeting, cancer therapy  Naz SWang MHan YHu BTeng LZhou JZhang HChen JDove Medical PressarticleMesoporous silica nanoparticlesdrug deliveryenzyme-responsivemultistage-targeting，cancer therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 2533-2542 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mesoporous silica nanoparticles drug delivery enzyme-responsive multistage-targeting，cancer therapy Medicine (General) R5-920
spellingShingle	Mesoporous silica nanoparticles drug delivery enzyme-responsive multistage-targeting，cancer therapy Medicine (General) R5-920 Naz S Wang M Han Y Hu B Teng L Zhou J Zhang H Chen J Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery
description	Safia Naz,1,* Mingyu Wang,1,* Yuning Han,1 Bin Hu,1 Liping Teng,2 Juan Zhou,1 Huijie Zhang,1 Jinghua Chen11Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China; 2Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China*These authors contributed equally to this workBackground: Drug delivery systems (DDS) capable of targeting both cell and organelle levels are highly desirable for effective cancer therapy. In this study, we developed a novel enzyme-responsive, multistage-targeted anticancer DDS based on mesoporous silica nanoparticles (MSNs), which possessed both CD44-targeting and mitochondrial-targeting properties.Materials and methods: Triphenylphosphine (TPP), a mitochondria-targeting compound, was grafted onto the surface of MSNs firstly. Then, Doxorubicin (Dox) was encapsulated into the pore of MSNs, followed by capping with tumor-targeting molecules hyaluronic acid (HA) through electrostatic interactions to form the final product consist of Dox loaded, TPP attached, HA capped mesoporous silica nanoparticles (MSN-DPH).Results: Our results suggested that MSN-DPH was preferentially taken up by cancer cells via CD44 receptor-mediated endocytosis. Moreover, MSN-DPH mainly accumulated in mitochondria owing to the mitochondrial-targeting ability of TPP. Degradation of HA by overexpressed HAase facilitated the release of Dox in cancer cells. Thus, MSN-DPH efficiently killed the cancer cells while exhibited much lower cytotoxicity to normal cells.Conclusion: This study demonstrates a promising multistage-targeted DDS for cancer chemotherapy.Keywords: mesoporous silica nanoparticles, drug delivery, enzyme-responsive, multistage-targeting, cancer therapy
format	article
author	Naz S Wang M Han Y Hu B Teng L Zhou J Zhang H Chen J
author_facet	Naz S Wang M Han Y Hu B Teng L Zhou J Zhang H Chen J
author_sort	Naz S
title	Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery
title_short	Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery
title_full	Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery
title_fullStr	Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery
title_full_unstemmed	Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery
title_sort	enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/88408b84325d4d08bef89d217d894edc
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Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery

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