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A mitochondria-targeted nano-platform for pancreatic cancer therapy

Liposome is a conventional drug delivery system which has been widely used in the pharmacy field. However, its applications are greatly restricted in clinical practice by the disadvantages of cholesterol and nonselective distribution. Herein, a novel platform for anti-tumor drug delivery was develop...

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Autores principales: Tan, Xiaoke, Zhu, Xin, Xu, Duanjie, Shi, Yanmei, Wang, Zhenzhen, Cao, Mingzhuo, Hu, Kai, Zhao, Lingzhou, Zhao, Junwei, Miao, Mingsan, Zeng, Huahui, Wu, Xiangxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533775/
https://www.ncbi.nlm.nih.gov/pubmed/36212077
http://dx.doi.org/10.3389/fchem.2022.951434
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author Tan, Xiaoke
Zhu, Xin
Xu, Duanjie
Shi, Yanmei
Wang, Zhenzhen
Cao, Mingzhuo
Hu, Kai
Zhao, Lingzhou
Zhao, Junwei
Miao, Mingsan
Zeng, Huahui
Wu, Xiangxiang
author_facet Tan, Xiaoke
Zhu, Xin
Xu, Duanjie
Shi, Yanmei
Wang, Zhenzhen
Cao, Mingzhuo
Hu, Kai
Zhao, Lingzhou
Zhao, Junwei
Miao, Mingsan
Zeng, Huahui
Wu, Xiangxiang
author_sort Tan, Xiaoke
collection PubMed
description Liposome is a conventional drug delivery system which has been widely used in the pharmacy field. However, its applications are greatly restricted in clinical practice by the disadvantages of cholesterol and nonselective distribution. Herein, a novel platform for anti-tumor drug delivery was developed by incorporating an amphiphilic stachydrine-octadecane conjugate (SS) as the mitochondria-targeting molecule onto the triptolide-liposome surfaces (SS-TP LPs). The polyethylene glycol (PEG) and the suitable particle size (about 133 nm) of liposomes facilitated their stabilities, the long half-life in blood and the escape from the rapid elimination. The SS-TP LPs were internalized and accumulated into the mitochondria of cancer cells in a time-dependent manner, followed by triggering permeabilization of the mitochondrial outer membrane by inhibiting Bcl-2, and then further caused greater cancer cell death via releasing cytochrome C and initiating a cascade of caspase 3 reactions. In the Pan02 tumor-bearing mice, the SS-TP LPs showed significant efficacy in inhibiting tumor growth and reducing tumor size but synchronously exhibited specific mitochondria-targeting and much lower subacute toxicity compared with the free TP and TP LPs. Our study suggests that SS-TP LPs can be a promising anticancer drug delivery system for mitochondria-targeted therapy in pancreatic cancer.
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spelling pubmed-95337752022-10-06 A mitochondria-targeted nano-platform for pancreatic cancer therapy Tan, Xiaoke Zhu, Xin Xu, Duanjie Shi, Yanmei Wang, Zhenzhen Cao, Mingzhuo Hu, Kai Zhao, Lingzhou Zhao, Junwei Miao, Mingsan Zeng, Huahui Wu, Xiangxiang Front Chem Chemistry Liposome is a conventional drug delivery system which has been widely used in the pharmacy field. However, its applications are greatly restricted in clinical practice by the disadvantages of cholesterol and nonselective distribution. Herein, a novel platform for anti-tumor drug delivery was developed by incorporating an amphiphilic stachydrine-octadecane conjugate (SS) as the mitochondria-targeting molecule onto the triptolide-liposome surfaces (SS-TP LPs). The polyethylene glycol (PEG) and the suitable particle size (about 133 nm) of liposomes facilitated their stabilities, the long half-life in blood and the escape from the rapid elimination. The SS-TP LPs were internalized and accumulated into the mitochondria of cancer cells in a time-dependent manner, followed by triggering permeabilization of the mitochondrial outer membrane by inhibiting Bcl-2, and then further caused greater cancer cell death via releasing cytochrome C and initiating a cascade of caspase 3 reactions. In the Pan02 tumor-bearing mice, the SS-TP LPs showed significant efficacy in inhibiting tumor growth and reducing tumor size but synchronously exhibited specific mitochondria-targeting and much lower subacute toxicity compared with the free TP and TP LPs. Our study suggests that SS-TP LPs can be a promising anticancer drug delivery system for mitochondria-targeted therapy in pancreatic cancer. Frontiers Media S.A. 2022-09-21 /pmc/articles/PMC9533775/ /pubmed/36212077 http://dx.doi.org/10.3389/fchem.2022.951434 Text en Copyright © 2022 Tan, Zhu, Xu, Shi, Wang, Cao, Hu, Zhao, Zhao, Miao, Zeng and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Tan, Xiaoke
Zhu, Xin
Xu, Duanjie
Shi, Yanmei
Wang, Zhenzhen
Cao, Mingzhuo
Hu, Kai
Zhao, Lingzhou
Zhao, Junwei
Miao, Mingsan
Zeng, Huahui
Wu, Xiangxiang
A mitochondria-targeted nano-platform for pancreatic cancer therapy
title A mitochondria-targeted nano-platform for pancreatic cancer therapy
title_full A mitochondria-targeted nano-platform for pancreatic cancer therapy
title_fullStr A mitochondria-targeted nano-platform for pancreatic cancer therapy
title_full_unstemmed A mitochondria-targeted nano-platform for pancreatic cancer therapy
title_short A mitochondria-targeted nano-platform for pancreatic cancer therapy
title_sort mitochondria-targeted nano-platform for pancreatic cancer therapy
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533775/
https://www.ncbi.nlm.nih.gov/pubmed/36212077
http://dx.doi.org/10.3389/fchem.2022.951434
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