Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy
Yu Xia, Tiantian Xu, Changbing Wang, Yinghua Li, Zhengfang Lin, Mingqi Zhao, Bing Zhu Central Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China Abstract: Human homeobox protein (Nanog) is highly expres...
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Dove Medical Press
2017
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oai:doaj.org-article:26553429a0df4e6b9181952ea7fb811a2021-12-02T06:34:20ZNovel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy1178-2013https://doaj.org/article/26553429a0df4e6b9181952ea7fb811a2017-12-01T00:00:00Zhttps://www.dovepress.com/novel-functionalized-nanoparticles-for-tumor-targeting-co-delivery-of--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yu Xia, Tiantian Xu, Changbing Wang, Yinghua Li, Zhengfang Lin, Mingqi Zhao, Bing Zhu Central Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China Abstract: Human homeobox protein (Nanog) is highly expressed in most cancer cells and has gradually emerged as an excellent target in cancer therapy, owing to its regulation of cancer cell proliferation, metastasis and apoptosis. In this study, we prepared tumor-targeting functionalized selenium nanoparticles (RGDfC-SeNPs) to load chemotherapeutic doxorubicin (DOX) and Nanog siRNA. Herein, RGDfC peptide was used as a tumor-targeting moiety which could specifically bind to αvβ3 integrins overexpressed on various cancer cells. The sizes of RGDfC-SeNPs@DOX nanoparticles (~12 nm) were confirmed by both dynamic light scattering and transmission electron microscopy. The chemical structure of RGDfC-SeNPs@DOX was characterized via Fourier-transform infrared spectroscopy. The RGDfC-SeNPs@DOX was compacted with siRNA (anti-Nanog) by electrostatic interaction to fabricate the RGDfC-SeNPs@DOX/siRNA complex. The RGDfC-SeNPs@DOX/siRNA complex nanoparticles could efficiently enter into HepG2 cells via clathrin-associated endocytosis, and showed high gene transfection efficiency that resulted in enhanced gene silencing. The in vivo biodistribution experiment indicated that RGDfC-SeNPs@DOX/siRNA nanoparticles were capable of specifically accumulating in the tumor site. Furthermore, treatment with RGDfC-SeNPs@DOX/siRNA resulted in a more significant anticancer activity than the free DOX, RGDfC-SeNPs@DOX or RGDfC-SeNPs/siRNA in vitro and in vivo. In summary, this study shows a novel type of DOX and siRNA co-delivery system, thereby providing an alternative route for cancer treatment. Keywords: nanoparticles, tumor targeting, drug delivery, doxorubicin, Nanog siRNAXia YXu TWang CLi YLin ZZhao MZhu BDove Medical Pressarticlenanoparticlestumor-targetingdrug deliverydoxorubicinNanog siRNAMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 143-159 (2017) |
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nanoparticles tumor-targeting drug delivery doxorubicin Nanog siRNA Medicine (General) R5-920 |
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nanoparticles tumor-targeting drug delivery doxorubicin Nanog siRNA Medicine (General) R5-920 Xia Y Xu T Wang C Li Y Lin Z Zhao M Zhu B Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy |
description |
Yu Xia, Tiantian Xu, Changbing Wang, Yinghua Li, Zhengfang Lin, Mingqi Zhao, Bing Zhu Central Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China Abstract: Human homeobox protein (Nanog) is highly expressed in most cancer cells and has gradually emerged as an excellent target in cancer therapy, owing to its regulation of cancer cell proliferation, metastasis and apoptosis. In this study, we prepared tumor-targeting functionalized selenium nanoparticles (RGDfC-SeNPs) to load chemotherapeutic doxorubicin (DOX) and Nanog siRNA. Herein, RGDfC peptide was used as a tumor-targeting moiety which could specifically bind to αvβ3 integrins overexpressed on various cancer cells. The sizes of RGDfC-SeNPs@DOX nanoparticles (~12 nm) were confirmed by both dynamic light scattering and transmission electron microscopy. The chemical structure of RGDfC-SeNPs@DOX was characterized via Fourier-transform infrared spectroscopy. The RGDfC-SeNPs@DOX was compacted with siRNA (anti-Nanog) by electrostatic interaction to fabricate the RGDfC-SeNPs@DOX/siRNA complex. The RGDfC-SeNPs@DOX/siRNA complex nanoparticles could efficiently enter into HepG2 cells via clathrin-associated endocytosis, and showed high gene transfection efficiency that resulted in enhanced gene silencing. The in vivo biodistribution experiment indicated that RGDfC-SeNPs@DOX/siRNA nanoparticles were capable of specifically accumulating in the tumor site. Furthermore, treatment with RGDfC-SeNPs@DOX/siRNA resulted in a more significant anticancer activity than the free DOX, RGDfC-SeNPs@DOX or RGDfC-SeNPs/siRNA in vitro and in vivo. In summary, this study shows a novel type of DOX and siRNA co-delivery system, thereby providing an alternative route for cancer treatment. Keywords: nanoparticles, tumor targeting, drug delivery, doxorubicin, Nanog siRNA |
format |
article |
author |
Xia Y Xu T Wang C Li Y Lin Z Zhao M Zhu B |
author_facet |
Xia Y Xu T Wang C Li Y Lin Z Zhao M Zhu B |
author_sort |
Xia Y |
title |
Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy |
title_short |
Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy |
title_full |
Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy |
title_fullStr |
Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy |
title_full_unstemmed |
Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy |
title_sort |
novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and sirna to enhance cancer therapy |
publisher |
Dove Medical Press |
publishDate |
2017 |
url |
https://doaj.org/article/26553429a0df4e6b9181952ea7fb811a |
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