Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784802414882193408 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9533775 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tanxiaoke amitochondriatargetednanoplatformforpancreaticcancertherapy AT zhuxin amitochondriatargetednanoplatformforpancreaticcancertherapy AT xuduanjie amitochondriatargetednanoplatformforpancreaticcancertherapy AT shiyanmei amitochondriatargetednanoplatformforpancreaticcancertherapy AT wangzhenzhen amitochondriatargetednanoplatformforpancreaticcancertherapy AT caomingzhuo amitochondriatargetednanoplatformforpancreaticcancertherapy AT hukai amitochondriatargetednanoplatformforpancreaticcancertherapy AT zhaolingzhou amitochondriatargetednanoplatformforpancreaticcancertherapy AT zhaojunwei amitochondriatargetednanoplatformforpancreaticcancertherapy AT miaomingsan amitochondriatargetednanoplatformforpancreaticcancertherapy AT zenghuahui amitochondriatargetednanoplatformforpancreaticcancertherapy AT wuxiangxiang amitochondriatargetednanoplatformforpancreaticcancertherapy AT tanxiaoke mitochondriatargetednanoplatformforpancreaticcancertherapy AT zhuxin mitochondriatargetednanoplatformforpancreaticcancertherapy AT xuduanjie mitochondriatargetednanoplatformforpancreaticcancertherapy AT shiyanmei mitochondriatargetednanoplatformforpancreaticcancertherapy AT wangzhenzhen mitochondriatargetednanoplatformforpancreaticcancertherapy AT caomingzhuo mitochondriatargetednanoplatformforpancreaticcancertherapy AT hukai mitochondriatargetednanoplatformforpancreaticcancertherapy AT zhaolingzhou mitochondriatargetednanoplatformforpancreaticcancertherapy AT zhaojunwei mitochondriatargetednanoplatformforpancreaticcancertherapy AT miaomingsan mitochondriatargetednanoplatformforpancreaticcancertherapy AT zenghuahui mitochondriatargetednanoplatformforpancreaticcancertherapy AT wuxiangxiang mitochondriatargetednanoplatformforpancreaticcancertherapy |