MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer
Abstract Background Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. Paris saponin VII (PSVII) could not only inhibit the proliferation of colon cancer cells...
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oai:doaj.org-article:dcf8c67b8de749f48595d7b0a10db6412021-11-21T12:29:26ZMCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer10.1186/s12951-021-01115-91477-3155https://doaj.org/article/dcf8c67b8de749f48595d7b0a10db6412021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01115-9https://doaj.org/toc/1477-3155Abstract Background Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. Paris saponin VII (PSVII) could not only inhibit the proliferation of colon cancer cells but also effectively induce apoptosis of drug-resistant colon cancer cells and reduce the metastasis of drug-resistant colon cancer cells as well. However, PSVII was insoluble in water and fat. It displayed no selective distribution in body and could cause severe hemolysis. Herein, colon cancer targeting calcium phosphate nanoparticles were developed to carry PSVII to treat drug-resistant colon cancer. Results PSVII carboxymethyl-β-cyclodextrin inclusion compound was successfully encapsulated in colon cancer targeting calcium phosphate nanoparticles (PSVII@MCP-CaP) by using modified citrus pectin as stabilizer agent and colon cancer cell targeting moiety. PSVII@MCP-CaP significantly reduced the hemolysis of PSVII. Moreover, by specific accumulating in orthotopic drug-resistant colon cancer tissue, PSVII@MCP-CaP markedly inhibited the growth of orthotopic drug-resistant colon cancer in nude mice. PSVII@MCP-CaP promoted the apoptosis of drug-resistant colon cancer cells through mitochondria-mediated apoptosis pathway. Moreover, PSVII@MCP-CaP significantly inhibited the invasion and migration of drug-resistant colon cancer cells by increasing E-cadherin protein expression and reducing N-cadherin and MMP-9 protein expression. Conclusion PSVII@MCP-CaP has great potential in the treatment of drug-resistant colon cancer. This study also explores a new method to prepare active targeting calcium phosphate nanoparticles loaded with a fat and water insoluble compound in water. Graphical AbstractShaobo BaiYang SunYing ChengWeiliang YeChenchao JiangMiao LiuQifeng JiBangle ZhangQibing MeiDaozhou LiuSiyuan ZhouBMCarticleParis saponin VIIModified citrus pectinDrug-resistant colon cancerColon cancer targeting drug delivery systemCalcium phosphate nanoparticlesBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-20 (2021) |
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DOAJ |
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EN |
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Paris saponin VII Modified citrus pectin Drug-resistant colon cancer Colon cancer targeting drug delivery system Calcium phosphate nanoparticles Biotechnology TP248.13-248.65 Medical technology R855-855.5 |
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Paris saponin VII Modified citrus pectin Drug-resistant colon cancer Colon cancer targeting drug delivery system Calcium phosphate nanoparticles Biotechnology TP248.13-248.65 Medical technology R855-855.5 Shaobo Bai Yang Sun Ying Cheng Weiliang Ye Chenchao Jiang Miao Liu Qifeng Ji Bangle Zhang Qibing Mei Daozhou Liu Siyuan Zhou MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer |
description |
Abstract Background Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. Paris saponin VII (PSVII) could not only inhibit the proliferation of colon cancer cells but also effectively induce apoptosis of drug-resistant colon cancer cells and reduce the metastasis of drug-resistant colon cancer cells as well. However, PSVII was insoluble in water and fat. It displayed no selective distribution in body and could cause severe hemolysis. Herein, colon cancer targeting calcium phosphate nanoparticles were developed to carry PSVII to treat drug-resistant colon cancer. Results PSVII carboxymethyl-β-cyclodextrin inclusion compound was successfully encapsulated in colon cancer targeting calcium phosphate nanoparticles (PSVII@MCP-CaP) by using modified citrus pectin as stabilizer agent and colon cancer cell targeting moiety. PSVII@MCP-CaP significantly reduced the hemolysis of PSVII. Moreover, by specific accumulating in orthotopic drug-resistant colon cancer tissue, PSVII@MCP-CaP markedly inhibited the growth of orthotopic drug-resistant colon cancer in nude mice. PSVII@MCP-CaP promoted the apoptosis of drug-resistant colon cancer cells through mitochondria-mediated apoptosis pathway. Moreover, PSVII@MCP-CaP significantly inhibited the invasion and migration of drug-resistant colon cancer cells by increasing E-cadherin protein expression and reducing N-cadherin and MMP-9 protein expression. Conclusion PSVII@MCP-CaP has great potential in the treatment of drug-resistant colon cancer. This study also explores a new method to prepare active targeting calcium phosphate nanoparticles loaded with a fat and water insoluble compound in water. Graphical Abstract |
format |
article |
author |
Shaobo Bai Yang Sun Ying Cheng Weiliang Ye Chenchao Jiang Miao Liu Qifeng Ji Bangle Zhang Qibing Mei Daozhou Liu Siyuan Zhou |
author_facet |
Shaobo Bai Yang Sun Ying Cheng Weiliang Ye Chenchao Jiang Miao Liu Qifeng Ji Bangle Zhang Qibing Mei Daozhou Liu Siyuan Zhou |
author_sort |
Shaobo Bai |
title |
MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer |
title_short |
MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer |
title_full |
MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer |
title_fullStr |
MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer |
title_full_unstemmed |
MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer |
title_sort |
mcp mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer |
publisher |
BMC |
publishDate |
2021 |
url |
https://doaj.org/article/dcf8c67b8de749f48595d7b0a10db641 |
work_keys_str_mv |
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