A pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis

Zeliang Wei,1,2 Haibo Wang,3 Guang Xin,1 Zhi Zeng,1 Shiyi Li,1 Yue Ming,1 Xiaoyu Zhang,1 Zhihua Xing,1 Li Li,2 Youping Li,1 Boli Zhang,1,4 Junhua Zhang,4 Hai Niu,1,5 Wen Huang1 1Laboratory of Ethnopharmacology, West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan, Peo...

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Autores principales:	Wei Z, Wang H, Xin G, Zeng Z, Li S, Ming Y, Zhang X, Xing Z, Li L, Li Y, Zhang B, Zhang J, Niu H, Huang W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	anti-metastasis antitumor self-assembly codelivery doxorubicin Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/28bb354395364cac988b36fee780b1d6
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spelling	oai:doaj.org-article:28bb354395364cac988b36fee780b1d62021-12-02T12:53:30ZA pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis1178-2013https://doaj.org/article/28bb354395364cac988b36fee780b1d62020-09-01T00:00:00Zhttps://www.dovepress.com/a-ph-sensitive-prodrug-nanocarrier-based-on-diosgenin-for-doxorubicin--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zeliang Wei,1,2 Haibo Wang,3 Guang Xin,1 Zhi Zeng,1 Shiyi Li,1 Yue Ming,1 Xiaoyu Zhang,1 Zhihua Xing,1 Li Li,2 Youping Li,1 Boli Zhang,1,4 Junhua Zhang,4 Hai Niu,1,5 Wen Huang1 1Laboratory of Ethnopharmacology, West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Textile Institute, College of Light Industry, Textile and Food Engineering, Sichuan University, Chengdu, People’s Republic of China; 4Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5College of Mathematics, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Wen Huang; Hai Niu Email huangwen@scu.edu.cn; niuhai@scu.edu.cnBackground: The metastasis, one of the biggest barriers in cancer therapy, is the leading cause of tumor deterioration and recurrence. The anti.-metastasis has been considered as a feasible strategy for clinical cancer management. It is well known that diosgenin could inhibit tumor metastasis and doxorubicin (DOX) could induce tumor apoptosis. However, their efficient delivery remains challenging.Purpose: To address these issues, a novel pH-sensitive polymer-prodrug based on diosgenin nanoparticles (NPs) platform was developed to enhance the efficiency of DOX delivery (DOX/NPs) for synergistic therapy of cutaneous melanoma, the most lethal form of skin cancer with high malignancy, early metastasis and high mortality.Methods and Results: The inhibitory effect of DOX/NPs on tumor proliferation and migration was superior to that of NPs or free DOX. What is more, DOX/NPs could combine mitochondria-associated metastasis and apoptosis with unique internalization pathway of carrier to fight tumors. In addition, biodistribution experiments proved that DOX/NPs could efficiently accumulate in tumor sites through enhancing permeation and retention (EPR) effect compared with free DOX. Importantly, the data from in vivo experiment revealed that DOX/NPs without heart toxicity significantly inhibited tumor metastasis by exerting synergistic therapeutic effect, and reduced tumor volume and weight by inducing apoptosis.Conclusion: The nanocarrier DOX/NPs with satisfying pharmaceutical characteristics based on the establishment of two different functional agents is a promising strategy for synergistically enhancing effects of cancer therapy.Keywords: anti-metastasis, antitumor, self-assembly, codelivery, doxorubicinWei ZWang HXin GZeng ZLi SMing YZhang XXing ZLi LLi YZhang BZhang JNiu HHuang WDove Medical Pressarticleanti-metastasisantitumorself-assemblycodeliverydoxorubicinMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 6545-6560 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	anti-metastasis antitumor self-assembly codelivery doxorubicin Medicine (General) R5-920
spellingShingle	anti-metastasis antitumor self-assembly codelivery doxorubicin Medicine (General) R5-920 Wei Z Wang H Xin G Zeng Z Li S Ming Y Zhang X Xing Z Li L Li Y Zhang B Zhang J Niu H Huang W A pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis
description	Zeliang Wei,1,2 Haibo Wang,3 Guang Xin,1 Zhi Zeng,1 Shiyi Li,1 Yue Ming,1 Xiaoyu Zhang,1 Zhihua Xing,1 Li Li,2 Youping Li,1 Boli Zhang,1,4 Junhua Zhang,4 Hai Niu,1,5 Wen Huang1 1Laboratory of Ethnopharmacology, West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Textile Institute, College of Light Industry, Textile and Food Engineering, Sichuan University, Chengdu, People’s Republic of China; 4Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5College of Mathematics, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Wen Huang; Hai Niu Email huangwen@scu.edu.cn; niuhai@scu.edu.cnBackground: The metastasis, one of the biggest barriers in cancer therapy, is the leading cause of tumor deterioration and recurrence. The anti.-metastasis has been considered as a feasible strategy for clinical cancer management. It is well known that diosgenin could inhibit tumor metastasis and doxorubicin (DOX) could induce tumor apoptosis. However, their efficient delivery remains challenging.Purpose: To address these issues, a novel pH-sensitive polymer-prodrug based on diosgenin nanoparticles (NPs) platform was developed to enhance the efficiency of DOX delivery (DOX/NPs) for synergistic therapy of cutaneous melanoma, the most lethal form of skin cancer with high malignancy, early metastasis and high mortality.Methods and Results: The inhibitory effect of DOX/NPs on tumor proliferation and migration was superior to that of NPs or free DOX. What is more, DOX/NPs could combine mitochondria-associated metastasis and apoptosis with unique internalization pathway of carrier to fight tumors. In addition, biodistribution experiments proved that DOX/NPs could efficiently accumulate in tumor sites through enhancing permeation and retention (EPR) effect compared with free DOX. Importantly, the data from in vivo experiment revealed that DOX/NPs without heart toxicity significantly inhibited tumor metastasis by exerting synergistic therapeutic effect, and reduced tumor volume and weight by inducing apoptosis.Conclusion: The nanocarrier DOX/NPs with satisfying pharmaceutical characteristics based on the establishment of two different functional agents is a promising strategy for synergistically enhancing effects of cancer therapy.Keywords: anti-metastasis, antitumor, self-assembly, codelivery, doxorubicin
format	article
author	Wei Z Wang H Xin G Zeng Z Li S Ming Y Zhang X Xing Z Li L Li Y Zhang B Zhang J Niu H Huang W
author_facet	Wei Z Wang H Xin G Zeng Z Li S Ming Y Zhang X Xing Z Li L Li Y Zhang B Zhang J Niu H Huang W
author_sort	Wei Z
title	A pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis
title_short	A pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis
title_full	A pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis
title_fullStr	A pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis
title_full_unstemmed	A pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis
title_sort	ph-sensitive prodrug nanocarrier based on diosgenin for doxorubicin delivery to efficiently inhibit tumor metastasis
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/28bb354395364cac988b36fee780b1d6
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A pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis

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