Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer

Jialang Zhuang,1,2,* Siqi Chen,1,3,* Ye Hu,1 Fan Yang,1 Qin Huo,1 Ni Xie1 1Biobank, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of China; 2Shenzhen Institute of Advanced Technology, Chinese Academy of Sc...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhuang J, Chen S, Hu Y, Yang F, Huo Q, Xie N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	drug delivery mesoporous silica nanoparticles dna aptamer controlled release metastatic breast cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6edf984760ae447999638bd7c08423b1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6edf984760ae447999638bd7c08423b1
record_format	dspace
spelling	oai:doaj.org-article:6edf984760ae447999638bd7c08423b12021-12-02T13:26:20ZTumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer1178-2013https://doaj.org/article/6edf984760ae447999638bd7c08423b12021-03-01T00:00:00Zhttps://www.dovepress.com/tumour-targeted-and-redox-responsive-mesoporous-silica-nanoparticles-f-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jialang Zhuang,1,2,* Siqi Chen,1,3,* Ye Hu,1 Fan Yang,1 Qin Huo,1 Ni Xie1 1Biobank, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of China; 2Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518035, People’s Republic of China; 3Graduate School of Guangzhou Medical University, Guangzhou, 510182, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ni Xie Email xn100@szu.edu.cnIntroduction: Metastatic breast cancer seriously harms women’s health and is currently the tumour type with the highest mortality rate in women. Recently, the combinatorial therapeutic approaches that integrate anti-cancer drugs and genetic agents is an attractive and promising strategy for the treatment of metastatic breast cancer. Moreover, such a combination strategy requires better drug carriers that can effectively deliver the cargo to the breast cancer cells and achieve controlled release in the cells to achieve better therapeutic effects.Methods: The tumour-targeted and redox-responsive mesoporous silica nanoparticles (MSNs) functionalised with DNA aptamers (AS1411) as a co-delivery system was developed and investigated for the potential against metastatic breast cancer. Doxorubicin (Dox) was loaded onto the MSNs, while AS1411 and a small interfering RNA (siTIE2) were employed as gatekeepers via attachment to the MSNs with redox-sensitive disulfide bonds.Results: The controlled release of Dox and siTIE2 was associated with intracellular glutathione. AS1411 mediated the targeted delivery of Dox by increasing its cellular uptake in metastatic breast cancer, ultimately resulting in a lower IC50 in MDA-MB-231 cells (human breast cancer cell line with high metastatic potency), improved biodistribution in tumour-bearing mice, and enhanced in vivo anti-tumour effects. The in vitro cell migration/invasion assay and in vivo anti-metastatic study revealed synergism in the co-delivery system that suppresses cancer cell metastasis.Conclusion: The tumour-targeted and redox-responsive MSN prepared in this study are promising for the effective delivery and controlled release of Dox and siTIE2 for improved treatment of metastatic breast cancer.Keywords: drug delivery, mesoporous silica nanoparticles, DNA aptamer, controlled release, metastatic breast cancerZhuang JChen SHu YYang FHuo QXie NDove Medical Pressarticledrug deliverymesoporous silica nanoparticlesdna aptamercontrolled releasemetastatic breast cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1961-1976 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug delivery mesoporous silica nanoparticles dna aptamer controlled release metastatic breast cancer Medicine (General) R5-920
spellingShingle	drug delivery mesoporous silica nanoparticles dna aptamer controlled release metastatic breast cancer Medicine (General) R5-920 Zhuang J Chen S Hu Y Yang F Huo Q Xie N Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer
description	Jialang Zhuang,1,2,* Siqi Chen,1,3,* Ye Hu,1 Fan Yang,1 Qin Huo,1 Ni Xie1 1Biobank, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of China; 2Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518035, People’s Republic of China; 3Graduate School of Guangzhou Medical University, Guangzhou, 510182, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ni Xie Email xn100@szu.edu.cnIntroduction: Metastatic breast cancer seriously harms women’s health and is currently the tumour type with the highest mortality rate in women. Recently, the combinatorial therapeutic approaches that integrate anti-cancer drugs and genetic agents is an attractive and promising strategy for the treatment of metastatic breast cancer. Moreover, such a combination strategy requires better drug carriers that can effectively deliver the cargo to the breast cancer cells and achieve controlled release in the cells to achieve better therapeutic effects.Methods: The tumour-targeted and redox-responsive mesoporous silica nanoparticles (MSNs) functionalised with DNA aptamers (AS1411) as a co-delivery system was developed and investigated for the potential against metastatic breast cancer. Doxorubicin (Dox) was loaded onto the MSNs, while AS1411 and a small interfering RNA (siTIE2) were employed as gatekeepers via attachment to the MSNs with redox-sensitive disulfide bonds.Results: The controlled release of Dox and siTIE2 was associated with intracellular glutathione. AS1411 mediated the targeted delivery of Dox by increasing its cellular uptake in metastatic breast cancer, ultimately resulting in a lower IC50 in MDA-MB-231 cells (human breast cancer cell line with high metastatic potency), improved biodistribution in tumour-bearing mice, and enhanced in vivo anti-tumour effects. The in vitro cell migration/invasion assay and in vivo anti-metastatic study revealed synergism in the co-delivery system that suppresses cancer cell metastasis.Conclusion: The tumour-targeted and redox-responsive MSN prepared in this study are promising for the effective delivery and controlled release of Dox and siTIE2 for improved treatment of metastatic breast cancer.Keywords: drug delivery, mesoporous silica nanoparticles, DNA aptamer, controlled release, metastatic breast cancer
format	article
author	Zhuang J Chen S Hu Y Yang F Huo Q Xie N
author_facet	Zhuang J Chen S Hu Y Yang F Huo Q Xie N
author_sort	Zhuang J
title	Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer
title_short	Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer
title_full	Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer
title_fullStr	Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer
title_full_unstemmed	Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer
title_sort	tumour-targeted and redox-responsive mesoporous silica nanoparticles for controlled release of doxorubicin and an sirna against metastatic breast cancer
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/6edf984760ae447999638bd7c08423b1
work_keys_str_mv	AT zhuangj tumourtargetedandredoxresponsivemesoporoussilicananoparticlesforcontrolledreleaseofdoxorubicinandansirnaagainstmetastaticbreastcancer AT chens tumourtargetedandredoxresponsivemesoporoussilicananoparticlesforcontrolledreleaseofdoxorubicinandansirnaagainstmetastaticbreastcancer AT huy tumourtargetedandredoxresponsivemesoporoussilicananoparticlesforcontrolledreleaseofdoxorubicinandansirnaagainstmetastaticbreastcancer AT yangf tumourtargetedandredoxresponsivemesoporoussilicananoparticlesforcontrolledreleaseofdoxorubicinandansirnaagainstmetastaticbreastcancer AT huoq tumourtargetedandredoxresponsivemesoporoussilicananoparticlesforcontrolledreleaseofdoxorubicinandansirnaagainstmetastaticbreastcancer AT xien tumourtargetedandredoxresponsivemesoporoussilicananoparticlesforcontrolledreleaseofdoxorubicinandansirnaagainstmetastaticbreastcancer
_version_	1718393035870437376

Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer

Ejemplares similares