pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy
Tianfeng Yang,1,* Guowen Du,2,* Yuxin Cui,1 Runze Yu,1 Chen Hua,2 Wei Tian,2,3 Yanmin Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; 2The Key Laboratory of Space Applied Physics and Chemistry Ministry of Educa...
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Dove Medical Press
2019
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oai:doaj.org-article:0ef6ae819a2a4956bf9613bec766997a2021-12-02T11:34:40ZpH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy1178-2013https://doaj.org/article/0ef6ae819a2a4956bf9613bec766997a2019-03-01T00:00:00Zhttps://www.dovepress.com/ph-sensitive-doxorubicin-loaded-polymeric-nanocomplex-based-on-beta-cy-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tianfeng Yang,1,* Guowen Du,2,* Yuxin Cui,1 Runze Yu,1 Chen Hua,2 Wei Tian,2,3 Yanmin Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; 2The Key Laboratory of Space Applied Physics and Chemistry Ministry of Education and Shanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi’an 710072, China; 3Xi’an Institute for Biomedical Materials and Engineering, Northwestern Polytechnical University, Xi’an 710072, China *These authors contributed equally to this work 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. Keywords: pH-sensitive, hepatocellular carcinoma, doxorubicin, drug deliveryYang TDu GCui YYu RHua CTian WZhang YDove Medical PressarticlepH-sensitivehepatocellular carcinomadoxorubicindrug deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1997-2010 (2019) |
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pH-sensitive hepatocellular carcinoma doxorubicin drug delivery Medicine (General) R5-920 |
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pH-sensitive hepatocellular carcinoma doxorubicin drug delivery Medicine (General) R5-920 Yang T Du G Cui Y Yu R Hua C Tian W Zhang Y pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy |
| description |
Tianfeng Yang,1,* Guowen Du,2,* Yuxin Cui,1 Runze Yu,1 Chen Hua,2 Wei Tian,2,3 Yanmin Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; 2The Key Laboratory of Space Applied Physics and Chemistry Ministry of Education and Shanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi’an 710072, China; 3Xi’an Institute for Biomedical Materials and Engineering, Northwestern Polytechnical University, Xi’an 710072, China *These authors contributed equally to this work 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. Keywords: pH-sensitive, hepatocellular carcinoma, doxorubicin, drug delivery |
| format |
article |
| author |
Yang T Du G Cui Y Yu R Hua C Tian W Zhang Y |
| author_facet |
Yang T Du G Cui Y Yu R Hua C Tian W Zhang Y |
| author_sort |
Yang T |
| title |
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_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_sort |
ph-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/0ef6ae819a2a4956bf9613bec766997a |
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