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pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy
BACKGROUND: Doxorubicin (DOX) is one of the most effective treatments for hepatocellular carcinoma (HCC), but is restricted by its poor pharmacokinetics. Herein, we exploited efficient targeted drug delivery systems and they have been found to be a worthy strategy for liver cancer therapy. MATERIALS...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433111/ https://www.ncbi.nlm.nih.gov/pubmed/30962684 http://dx.doi.org/10.2147/IJN.S193170 |
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author | Yang, Tianfeng Du, Guowen Cui, Yuxin Yu, Runze Hua, Chen Tian, Wei Zhang, Yanmin |
author_facet | Yang, Tianfeng Du, Guowen Cui, Yuxin Yu, Runze Hua, Chen Tian, Wei Zhang, Yanmin |
author_sort | Yang, Tianfeng |
collection | PubMed |
description | BACKGROUND: Doxorubicin (DOX) is one of the most effective treatments for hepatocellular carcinoma (HCC), but is restricted by its poor pharmacokinetics. Herein, we exploited efficient targeted drug delivery systems and they have been found to be a worthy strategy for liver cancer therapy. MATERIALS AND METHODS: We investigated polymeric nanoparticles which were synthesized based on host–guest interaction between β-cyclodextrin and benzimidazole. The properties of nanoparticles with regard to size/shape, encapsulation efficiency, and drug release were investigated using conventional experiments. Cell proliferation assay in vitro, cell uptake assay, and cell apoptosis analysis were used to investigate cytotoxicity, uptake, and mechanism of targeted supramolecular prodrug complexes (TSPCs)-based self-assemblies and supramolecular prodrug complexes (SPCs)-based self-assemblies. RESULTS: The pH-sensitive lactobionic acid (LA)-modified pH-sensitive self-assemblies were synthesized successfully. The results of in vitro released assay showed that the accelerated released of DOX from TSPCs-based self-assemblies with the decrease of pH value. When TSPCs-based self-assemblies were taken up by HepG2 cells, they demonstrated a faster release rate under acidic conditions and proved to have higher cytotoxicity than in the presence of LA. A mechanistic study revealed that TSPCs-based self-assemblies inhibited liver cell proliferation by inducing cell apoptosis. CONCLUSION: The pH-sensitive nanocomplex, as liver-targeted nanoparticles, facilitated the efficacy of DOX in HepG2 cells, offering an appealing strategy for the treatment of HCC. |
format | Online Article Text |
id | pubmed-6433111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64331112019-04-08 pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy Yang, Tianfeng Du, Guowen Cui, Yuxin Yu, Runze Hua, Chen Tian, Wei Zhang, Yanmin Int J Nanomedicine Original Research BACKGROUND: Doxorubicin (DOX) is one of the most effective treatments for hepatocellular carcinoma (HCC), but is restricted by its poor pharmacokinetics. Herein, we exploited efficient targeted drug delivery systems and they have been found to be a worthy strategy for liver cancer therapy. MATERIALS AND METHODS: We investigated polymeric nanoparticles which were synthesized based on host–guest interaction between β-cyclodextrin and benzimidazole. The properties of nanoparticles with regard to size/shape, encapsulation efficiency, and drug release were investigated using conventional experiments. Cell proliferation assay in vitro, cell uptake assay, and cell apoptosis analysis were used to investigate cytotoxicity, uptake, and mechanism of targeted supramolecular prodrug complexes (TSPCs)-based self-assemblies and supramolecular prodrug complexes (SPCs)-based self-assemblies. RESULTS: The pH-sensitive lactobionic acid (LA)-modified pH-sensitive self-assemblies were synthesized successfully. The results of in vitro released assay showed that the accelerated released of DOX from TSPCs-based self-assemblies with the decrease of pH value. When TSPCs-based self-assemblies were taken up by HepG2 cells, they demonstrated a faster release rate under acidic conditions and proved to have higher cytotoxicity than in the presence of LA. A mechanistic study revealed that TSPCs-based self-assemblies inhibited liver cell proliferation by inducing cell apoptosis. CONCLUSION: The pH-sensitive nanocomplex, as liver-targeted nanoparticles, facilitated the efficacy of DOX in HepG2 cells, offering an appealing strategy for the treatment of HCC. Dove Medical Press 2019-03-21 /pmc/articles/PMC6433111/ /pubmed/30962684 http://dx.doi.org/10.2147/IJN.S193170 Text en © 2019 Yang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Yang, Tianfeng Du, Guowen Cui, Yuxin Yu, Runze Hua, Chen Tian, Wei Zhang, Yanmin pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy |
title | pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy |
title_full | pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy |
title_fullStr | pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy |
title_full_unstemmed | pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy |
title_short | pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy |
title_sort | ph-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433111/ https://www.ncbi.nlm.nih.gov/pubmed/30962684 http://dx.doi.org/10.2147/IJN.S193170 |
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