pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery

Yao Yao, Zhihui Su, Yanchao Liang, Na Zhang School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People’s Republic of China Abstract: Combination of chemotherapeutic drug and small interfering RNA (siRNA) can affect multiple disease pathways and has been proven effect...

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Autores principales:	Yao Y, Su ZH, Liang YC, Zhang N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a386be9d49d646b9962dab41e64a3fbe
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spelling	oai:doaj.org-article:a386be9d49d646b9962dab41e64a3fbe2021-12-02T05:40:29ZpH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery1178-2013https://doaj.org/article/a386be9d49d646b9962dab41e64a3fbe2015-10-01T00:00:00Zhttps://www.dovepress.com/ph-sensitive-carboxymethyl-chitosan-modified-cationic-liposomes-for-so-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yao Yao, Zhihui Su, Yanchao Liang, Na Zhang School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People’s Republic of China Abstract: Combination of chemotherapeutic drug and small interfering RNA (siRNA) can affect multiple disease pathways and has been proven effective in suppressing tumor progression. Co-delivery of drug and siRNA within a same nanocarrier is a vital means in this field. The present study aimed at the development of a pH-sensitive liposome to co-deliver drug and siRNA to tumor region. Driven by the electrostatic interaction, the pH-sensitive material, carboxymethyl chitosan (CMCS), was coated onto the surface of the cationic liposome (CL) preloaded with sorafenib (Sf) and siRNA (Si). To evaluate whether the resulting CMCS-modified Sf and siRNA co-delivery cationic liposome (CMCS-SiSf-CL) enhanced antitumor efficiency after systematic administration, in vitro and in vivo experiments were evaluated in HepG2 cells and the H22 cells-bearing Kunming mice model. The experimental results demonstrated that CMCS-SiSf-CL was able to condense siRNA efficiently and protect siRNA from being degraded by serum and RNase. The release rate of Sf from CMCS-modified liposome exhibited pH-sensitive release behavior. Furthermore, in vitro cellular uptake results showed that CMCS-SiSf-CL yielded higher fluorescence intensity at pH 6.5 than at pH 7.4, and that siRNA could be delivered to tumor site by CMCS-SiSf-CL in vivo. The in vivo antitumor efficacy showed that CMCS-Sf-CL inhibits tumor growth effectively when compared with free Sf solution. In current experimental conditions, this liposomal formulation did not show significant toxicity both in vitro and in vivo. Therefore, co-delivering Sf with siRNA by CMCS-SiSf-CL might provide a promising approach for tumor therapy. Keywords: co-delivery, sorafenib, gene, charge conversion, cancer therapyYao YSu ZHLiang YCZhang NDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6185-6198 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Yao Y Su ZH Liang YC Zhang N pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery
description	Yao Yao, Zhihui Su, Yanchao Liang, Na Zhang School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People’s Republic of China Abstract: Combination of chemotherapeutic drug and small interfering RNA (siRNA) can affect multiple disease pathways and has been proven effective in suppressing tumor progression. Co-delivery of drug and siRNA within a same nanocarrier is a vital means in this field. The present study aimed at the development of a pH-sensitive liposome to co-deliver drug and siRNA to tumor region. Driven by the electrostatic interaction, the pH-sensitive material, carboxymethyl chitosan (CMCS), was coated onto the surface of the cationic liposome (CL) preloaded with sorafenib (Sf) and siRNA (Si). To evaluate whether the resulting CMCS-modified Sf and siRNA co-delivery cationic liposome (CMCS-SiSf-CL) enhanced antitumor efficiency after systematic administration, in vitro and in vivo experiments were evaluated in HepG2 cells and the H22 cells-bearing Kunming mice model. The experimental results demonstrated that CMCS-SiSf-CL was able to condense siRNA efficiently and protect siRNA from being degraded by serum and RNase. The release rate of Sf from CMCS-modified liposome exhibited pH-sensitive release behavior. Furthermore, in vitro cellular uptake results showed that CMCS-SiSf-CL yielded higher fluorescence intensity at pH 6.5 than at pH 7.4, and that siRNA could be delivered to tumor site by CMCS-SiSf-CL in vivo. The in vivo antitumor efficacy showed that CMCS-Sf-CL inhibits tumor growth effectively when compared with free Sf solution. In current experimental conditions, this liposomal formulation did not show significant toxicity both in vitro and in vivo. Therefore, co-delivering Sf with siRNA by CMCS-SiSf-CL might provide a promising approach for tumor therapy. Keywords: co-delivery, sorafenib, gene, charge conversion, cancer therapy
format	article
author	Yao Y Su ZH Liang YC Zhang N
author_facet	Yao Y Su ZH Liang YC Zhang N
author_sort	Yao Y
title	pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery
title_short	pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery
title_full	pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery
title_fullStr	pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery
title_full_unstemmed	pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery
title_sort	ph-sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and sirna co-delivery
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/a386be9d49d646b9962dab41e64a3fbe
work_keys_str_mv	AT yaoy phsensitivecarboxymethylchitosanmodifiedcationicliposomesforsorafenibandsirnacodelivery AT suzh phsensitivecarboxymethylchitosanmodifiedcationicliposomesforsorafenibandsirnacodelivery AT liangyc phsensitivecarboxymethylchitosanmodifiedcationicliposomesforsorafenibandsirnacodelivery AT zhangn phsensitivecarboxymethylchitosanmodifiedcationicliposomesforsorafenibandsirnacodelivery
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pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery

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