Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII

Lu Lu,1 Yue Ding,2 Yong Zhang,2 Rodney JY Ho,3 Yuan Zhao,4 Tong Zhang,1 Chunrong Guo2 1School of Pharmacy, 2Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3Department of Pharmaceutics, University of Washington, Seattle, WA, USA; 4C...

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Autores principales:	Lu L, Ding Yue, Zhang Y, Ho RJY, Zhao Y, Zhang T, Guo C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	timosaponin AIII liposomes CD44 tumor-targeting drug delivery receptor mediated drug targeting Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8d06d0ccec064df6a0466efd19e67947
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spelling	oai:doaj.org-article:8d06d0ccec064df6a0466efd19e679472021-12-02T06:09:47ZAntibody-modified liposomes for tumor-targeting delivery of timosaponin AIII1178-2013https://doaj.org/article/8d06d0ccec064df6a0466efd19e679472018-03-01T00:00:00Zhttps://www.dovepress.com/antibody-modified-liposomes-for-tumor-targeting-delivery-of-timosaponi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lu Lu,1 Yue Ding,2 Yong Zhang,2 Rodney JY Ho,3 Yuan Zhao,4 Tong Zhang,1 Chunrong Guo2 1School of Pharmacy, 2Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3Department of Pharmaceutics, University of Washington, Seattle, WA, USA; 4Center of Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China Introduction: Timosaponin AIII (TAIII), as a steroid saponin in Anemarrhena asphodeloides, has favorable potential as an antitumor candidate. However, its hydrophobicity and low bioavailability severely limit its in vivo antitumor efficacy. Methods: To overcome this drawback, TAIII-loaded liposomes (LP) were prepared to improve TAIII solubility and extend its circulation time. Furthermore, anti-CD44 antibody-modified LP (CD44-LP) was prepared to enhance the therapeutic index of TAIII. The LP and CD44-LP were also characterized through their biological activity, target selective binding and uptake, and in vivo pharmacokinetics. Results: Compared with free TAIII, both LP and CD44-LP possessed a desirable sustained-release profile in vitro, with ~14.2- and 10.7-fold longer TAIII half-life, respectively, and 1.7- and 1.9-fold larger area under the curve, respectively. LP and CD44-LP enhanced TAIII antitumor activity against HepG2 cells and in a xenograft mouse model without detectable toxicity. In particular, CD44-LP exhibited notably higher cytotoxicity than did LP, with a lower half-maximal inhibitory concentration (48 h). CD44-LP exhibited stronger tumor inhibition, and the tumor inhibitory effect was 1.3-fold that of LP. Furthermore, confocal laser scanning microscopy and in vivo near-infrared imaging of a xenograft mouse model revealed that compared with LP, CD44-LP could effectively enhance tumor accumulation. Conclusion: Taken together, the results indicate that both CD44-LP and LP can considerably extend TAIII circulation time, increase tumor-targeted accumulation, and enhance antitumor activity. Thus, the anti-CD44 antibody-modified liposome is a promising candidate for treating CD44-positive cancer with considerable antitumor effects. Keywords: timosaponin AIII, liposomes, CD44, tumor-targeting drug delivery, receptor-mediated drug targetingLu LDing YueZhang YHo RJYZhao YZhang TGuo CDove Medical Pressarticletimosaponin AIIIliposomesCD44tumor-targeting drug deliveryreceptor mediated drug targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1927-1944 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	timosaponin AIII liposomes CD44 tumor-targeting drug delivery receptor mediated drug targeting Medicine (General) R5-920
spellingShingle	timosaponin AIII liposomes CD44 tumor-targeting drug delivery receptor mediated drug targeting Medicine (General) R5-920 Lu L Ding Yue Zhang Y Ho RJY Zhao Y Zhang T Guo C Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII
description	Lu Lu,1 Yue Ding,2 Yong Zhang,2 Rodney JY Ho,3 Yuan Zhao,4 Tong Zhang,1 Chunrong Guo2 1School of Pharmacy, 2Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3Department of Pharmaceutics, University of Washington, Seattle, WA, USA; 4Center of Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China Introduction: Timosaponin AIII (TAIII), as a steroid saponin in Anemarrhena asphodeloides, has favorable potential as an antitumor candidate. However, its hydrophobicity and low bioavailability severely limit its in vivo antitumor efficacy. Methods: To overcome this drawback, TAIII-loaded liposomes (LP) were prepared to improve TAIII solubility and extend its circulation time. Furthermore, anti-CD44 antibody-modified LP (CD44-LP) was prepared to enhance the therapeutic index of TAIII. The LP and CD44-LP were also characterized through their biological activity, target selective binding and uptake, and in vivo pharmacokinetics. Results: Compared with free TAIII, both LP and CD44-LP possessed a desirable sustained-release profile in vitro, with ~14.2- and 10.7-fold longer TAIII half-life, respectively, and 1.7- and 1.9-fold larger area under the curve, respectively. LP and CD44-LP enhanced TAIII antitumor activity against HepG2 cells and in a xenograft mouse model without detectable toxicity. In particular, CD44-LP exhibited notably higher cytotoxicity than did LP, with a lower half-maximal inhibitory concentration (48 h). CD44-LP exhibited stronger tumor inhibition, and the tumor inhibitory effect was 1.3-fold that of LP. Furthermore, confocal laser scanning microscopy and in vivo near-infrared imaging of a xenograft mouse model revealed that compared with LP, CD44-LP could effectively enhance tumor accumulation. Conclusion: Taken together, the results indicate that both CD44-LP and LP can considerably extend TAIII circulation time, increase tumor-targeted accumulation, and enhance antitumor activity. Thus, the anti-CD44 antibody-modified liposome is a promising candidate for treating CD44-positive cancer with considerable antitumor effects. Keywords: timosaponin AIII, liposomes, CD44, tumor-targeting drug delivery, receptor-mediated drug targeting
format	article
author	Lu L Ding Yue Zhang Y Ho RJY Zhao Y Zhang T Guo C
author_facet	Lu L Ding Yue Zhang Y Ho RJY Zhao Y Zhang T Guo C
author_sort	Lu L
title	Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII
title_short	Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII
title_full	Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII
title_fullStr	Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII
title_full_unstemmed	Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII
title_sort	antibody-modified liposomes for tumor-targeting delivery of timosaponin aiii
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/8d06d0ccec064df6a0466efd19e67947
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Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII

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