MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer

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...

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Autores principales: Bai, Shaobo, Sun, Yang, Cheng, Ying, Ye, Weiliang, Jiang, Chenchao, Liu, Miao, Ji, Qifeng, Zhang, Bangle, Mei, Qibing, Liu, Daozhou, Zhou, Siyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600743/
https://www.ncbi.nlm.nih.gov/pubmed/34789268
http://dx.doi.org/10.1186/s12951-021-01115-9
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author Bai, Shaobo
Sun, Yang
Cheng, Ying
Ye, Weiliang
Jiang, Chenchao
Liu, Miao
Ji, Qifeng
Zhang, Bangle
Mei, Qibing
Liu, Daozhou
Zhou, Siyuan
author_facet Bai, Shaobo
Sun, Yang
Cheng, Ying
Ye, Weiliang
Jiang, Chenchao
Liu, Miao
Ji, Qifeng
Zhang, Bangle
Mei, Qibing
Liu, Daozhou
Zhou, Siyuan
author_sort Bai, Shaobo
collection PubMed
description 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-01115-9.
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spelling pubmed-86007432021-11-19 MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer Bai, Shaobo Sun, Yang Cheng, Ying Ye, Weiliang Jiang, Chenchao Liu, Miao Ji, Qifeng Zhang, Bangle Mei, Qibing Liu, Daozhou Zhou, Siyuan J Nanobiotechnology Research 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-01115-9. BioMed Central 2021-11-17 /pmc/articles/PMC8600743/ /pubmed/34789268 http://dx.doi.org/10.1186/s12951-021-01115-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Bai, Shaobo
Sun, Yang
Cheng, Ying
Ye, Weiliang
Jiang, Chenchao
Liu, Miao
Ji, Qifeng
Zhang, Bangle
Mei, Qibing
Liu, Daozhou
Zhou, Siyuan
MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer
title 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_short 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600743/
https://www.ncbi.nlm.nih.gov/pubmed/34789268
http://dx.doi.org/10.1186/s12951-021-01115-9
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