Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer

Wenhua Zhang,1,2,* Wenhua Xu,1,* Yu Lan,3 Xuliang He,1 Kaibin Liu,4 Ye Liang21Department of Inspection, Medical Faculty, Qingdao University, Qingdao 266003, People’s Republic of China; 2Key Laboratory, Department of Urology and Andrology, Affiliated Hospital of Qingdao University,...

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Autores principales: Zhang W, Xu W, Lan Y, He X, Liu K, Liang Y
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:a8858cc1d5614f82a25fcec081abb7412021-12-02T03:06:29ZAntitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer1178-2013https://doaj.org/article/a8858cc1d5614f82a25fcec081abb7412019-07-01T00:00:00Zhttps://www.dovepress.com/antitumor-effect-of-hyaluronic-acid-modified-chitosan-nanoparticles-lo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wenhua Zhang,1,2,* Wenhua Xu,1,* Yu Lan,3 Xuliang He,1 Kaibin Liu,4 Ye Liang21Department of Inspection, Medical Faculty, Qingdao University, Qingdao 266003, People’s Republic of China; 2Key Laboratory, Department of Urology and Andrology, Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of China; 3Department of Inspection, Weihai Central Hospital, Weihai 264400, People’s Republic of China; 4Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workPurpose: Nanoparticle (NP)-mediated targeted delivery of therapeutic genes or siRNAs to tumors has potential advantages. In this study, hyaluronic acid (HA)-modified chitosan nanoparticles (CS NPs-HA) loaded with cyanine 3 (Cy3)-labeled siRNA (sCS NPs-HA) were prepared and characterized.Methods: Human non-small cell lung cancer (NSCLC) A549 cells expressing receptor CD44 and tumor-bearing mice were used to evaluate the cytotoxic and antitumor effects of sCS NPs-HA in vitro and in vivo.Results: The results showed that noncytotoxic CS NPs-HA of small size (100–200 nm) effectively delivered the Cy3-labeled siRNA to A549 cells via receptor CD44 and inhibited cell proliferation by downregulating the target gene BCL2. In vivo experiment results revealed that sCS NPs-HA directly delivered greater amounts of Cy3-labeled siRNA to the tumor sites, resulting in the inhibition of tumor growth by downregulating BCL2, as compared to unmodified NPs loaded with siRNA (sCS NPs) and to naked Cy3-labeled siRNA.Conclusion: The HA-modified NPs based on chitosan could serve as a promising carrier for siRNA delivery and targeted therapy for NSCLC expressing CD44.Keywords: nanoparticle, siRNA, CD44, hyaluronic acid, cancerZhang WXu WLan YHe XLiu KLiang YDove Medical PressarticlenanoparticlesiRNACD44hyaluronic acidcancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5287-5301 (2019)
institution DOAJ
collection DOAJ
language EN
topic nanoparticle
siRNA
CD44
hyaluronic acid
cancer
Medicine (General)
R5-920
spellingShingle nanoparticle
siRNA
CD44
hyaluronic acid
cancer
Medicine (General)
R5-920
Zhang W
Xu W
Lan Y
He X
Liu K
Liang Y
Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer
description Wenhua Zhang,1,2,* Wenhua Xu,1,* Yu Lan,3 Xuliang He,1 Kaibin Liu,4 Ye Liang21Department of Inspection, Medical Faculty, Qingdao University, Qingdao 266003, People’s Republic of China; 2Key Laboratory, Department of Urology and Andrology, Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of China; 3Department of Inspection, Weihai Central Hospital, Weihai 264400, People’s Republic of China; 4Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workPurpose: Nanoparticle (NP)-mediated targeted delivery of therapeutic genes or siRNAs to tumors has potential advantages. In this study, hyaluronic acid (HA)-modified chitosan nanoparticles (CS NPs-HA) loaded with cyanine 3 (Cy3)-labeled siRNA (sCS NPs-HA) were prepared and characterized.Methods: Human non-small cell lung cancer (NSCLC) A549 cells expressing receptor CD44 and tumor-bearing mice were used to evaluate the cytotoxic and antitumor effects of sCS NPs-HA in vitro and in vivo.Results: The results showed that noncytotoxic CS NPs-HA of small size (100–200 nm) effectively delivered the Cy3-labeled siRNA to A549 cells via receptor CD44 and inhibited cell proliferation by downregulating the target gene BCL2. In vivo experiment results revealed that sCS NPs-HA directly delivered greater amounts of Cy3-labeled siRNA to the tumor sites, resulting in the inhibition of tumor growth by downregulating BCL2, as compared to unmodified NPs loaded with siRNA (sCS NPs) and to naked Cy3-labeled siRNA.Conclusion: The HA-modified NPs based on chitosan could serve as a promising carrier for siRNA delivery and targeted therapy for NSCLC expressing CD44.Keywords: nanoparticle, siRNA, CD44, hyaluronic acid, cancer
format article
author Zhang W
Xu W
Lan Y
He X
Liu K
Liang Y
author_facet Zhang W
Xu W
Lan Y
He X
Liu K
Liang Y
author_sort Zhang W
title Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer
title_short Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer
title_full Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer
title_fullStr Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer
title_full_unstemmed Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer
title_sort antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with sirna for targeted therapy for non-small cell lung cancer
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/a8858cc1d5614f82a25fcec081abb741
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