Tumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide

Chong Li,1,2 Yixin Wang,3 Xiaolin Zhang,1 Li Deng,1 Yan Zhang,1 Zhangbao Chen1 1Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, People&#39;s Republic of China; 2School of Pharmacy, Key Laborato...

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Autores principales:	Li C, Wang Y, Zhang X, Deng L, Zhang Y, Chen Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c404150c81c7451c9c66e4ccdcc7d117
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spelling	oai:doaj.org-article:c404150c81c7451c9c66e4ccdcc7d1172021-12-02T02:46:50ZTumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide1176-91141178-2013https://doaj.org/article/c404150c81c7451c9c66e4ccdcc7d1172013-03-01T00:00:00Zhttp://www.dovepress.com/tumor-targeted-liposomal-drug-delivery-mediated-by-a-diseleno-bond-sta-a12446https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Chong Li,1,2 Yixin Wang,3 Xiaolin Zhang,1 Li Deng,1 Yan Zhang,1 Zhangbao Chen1 1Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, People&#39;s Republic of China; 2School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Fudan University, Shanghai, People&#39;s Republic of China; 3Department of Pharmacy, the Second People&#39;s Hospital of Sichuan Province and Sichuan Cancer Hospital, Chengdu, People&#39;s Republic of China Abstract: Peptide ligands have played an important role in tumor-targeted drug delivery as targeting moieties. The in vivo fate of peptide-mediated drug delivery systems and the following antitumor effects may greatly depend on the stability of the peptide ligand. In the current study, a tumor-targeting cyclic peptide screened by phage display, Lyp-1 (a peptide that specifically binds to tumor and endothelial cells of tumor lymphatics in certain tumors), was structurally modified by replacement of the original intramolecular disulfide bond with a diseleno bond. The produced analog Syp-1 (seleno derivative of Lyp-1) maintained specific binding ability to the target protein p32 (Kd = 18.54 nM), which is similar to that of Lyp-1 (Kd = 10.59 nM), indicated by surface plasmon resonance assay. Compared with Lyp-1, Syp-1 showed significantly improved stability against serum. After the peptide attached onto the surface of fluorophore-encapsulating liposomes, the more efficient tumor uptake of liposomal fluorophore mediated by Syp-1 was observed. Furthermore, Syp-1 modified liposomal doxorubicin presented the most potent tumor growth inhibitory ability among all the therapeutic groups, with a low half maximal inhibitory concentration of 588 nM against MDA-MB-435 cells in vitro and a high tumor inhibition rate of 73.5% in vivo. These findings clearly indicated that Syp-1 was a stable and effective tumor targeting ligand and suggest that the sulfur-to-selenium replacement strategy may help stabilize the phage-displayed cyclic peptide containing disulfide-bond under physiological conditions and strongly support the validity of peptide-mediated drug targeting. Keywords: tumor targeting, liposome, cyclic peptide, selenopeptideLi CWang YZhang XDeng LZhang YChen ZDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1051-1062 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li C Wang Y Zhang X Deng L Zhang Y Chen Z Tumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide
description	Chong Li,1,2 Yixin Wang,3 Xiaolin Zhang,1 Li Deng,1 Yan Zhang,1 Zhangbao Chen1 1Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, People&#39;s Republic of China; 2School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Fudan University, Shanghai, People&#39;s Republic of China; 3Department of Pharmacy, the Second People&#39;s Hospital of Sichuan Province and Sichuan Cancer Hospital, Chengdu, People&#39;s Republic of China Abstract: Peptide ligands have played an important role in tumor-targeted drug delivery as targeting moieties. The in vivo fate of peptide-mediated drug delivery systems and the following antitumor effects may greatly depend on the stability of the peptide ligand. In the current study, a tumor-targeting cyclic peptide screened by phage display, Lyp-1 (a peptide that specifically binds to tumor and endothelial cells of tumor lymphatics in certain tumors), was structurally modified by replacement of the original intramolecular disulfide bond with a diseleno bond. The produced analog Syp-1 (seleno derivative of Lyp-1) maintained specific binding ability to the target protein p32 (Kd = 18.54 nM), which is similar to that of Lyp-1 (Kd = 10.59 nM), indicated by surface plasmon resonance assay. Compared with Lyp-1, Syp-1 showed significantly improved stability against serum. After the peptide attached onto the surface of fluorophore-encapsulating liposomes, the more efficient tumor uptake of liposomal fluorophore mediated by Syp-1 was observed. Furthermore, Syp-1 modified liposomal doxorubicin presented the most potent tumor growth inhibitory ability among all the therapeutic groups, with a low half maximal inhibitory concentration of 588 nM against MDA-MB-435 cells in vitro and a high tumor inhibition rate of 73.5% in vivo. These findings clearly indicated that Syp-1 was a stable and effective tumor targeting ligand and suggest that the sulfur-to-selenium replacement strategy may help stabilize the phage-displayed cyclic peptide containing disulfide-bond under physiological conditions and strongly support the validity of peptide-mediated drug targeting. Keywords: tumor targeting, liposome, cyclic peptide, selenopeptide
format	article
author	Li C Wang Y Zhang X Deng L Zhang Y Chen Z
author_facet	Li C Wang Y Zhang X Deng L Zhang Y Chen Z
author_sort	Li C
title	Tumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide
title_short	Tumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide
title_full	Tumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide
title_fullStr	Tumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide
title_full_unstemmed	Tumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide
title_sort	tumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/c404150c81c7451c9c66e4ccdcc7d117
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Tumor-targeted liposomal drug delivery mediated by a diseleno bond-stabilized cyclic peptide

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