Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides

Jiawei Sun,1 Lei Jiang,2 Yi Lin,3 Ethan Michael Gerhard,4 Xuehua Jiang,1 Li Li,3 Jian Yang,4 Zhongwei Gu3 1West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu, 3National Engineering Research Center for...

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Autores principales:	Sun J, Jiang L, Lin Y, Gerhard EM, Jiang X, Li L, Yang J, Gu Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	multistage tumor-targeting liposome mitochondria paclitaxel (PTX) anticancer anti-angiogenesis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1e046999938b4a6791bc72ee3e1e486f
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spelling	oai:doaj.org-article:1e046999938b4a6791bc72ee3e1e486f2021-12-02T02:49:03ZEnhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides1178-2013https://doaj.org/article/1e046999938b4a6791bc72ee3e1e486f2017-02-01T00:00:00Zhttps://www.dovepress.com/enhanced-anticancer-efficacy-of-paclitaxel-through-multistage-tumor-ta-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jiawei Sun,1 Lei Jiang,2 Yi Lin,3 Ethan Michael Gerhard,4 Xuehua Jiang,1 Li Li,3 Jian Yang,4 Zhongwei Gu3 1West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu, 3National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Biomedical Engineering Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, USA Abstract: Mitochondria serve as both “energy factories” and “suicide weapon stores” of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy. Here, multistage tumor-targeting liposomes containing two targeted peptide-modified lipids, cRGD-PEG2000-DSPE and KLA-PEG2000-DSPE, were developed for encapsulation of the anticancer drug paclitaxel (PTX, RGD-KLA/PTX-Lips). Compared with Taxol (free PTX), RGD/PTX-Lips and KLA/PTX-Lips, the half-maximal inhibitory concentration (IC50) value of RGD-KLA/PTX-Lips in vitro was 1.9-, 36.7- and 22.7-fold lower with 4T1 cells, respectively, because of higher levels of cellular uptake. Similar results were also observed with human umbilical vascular endothelial cells (HUVECs). An apoptosis assay showed that the total apoptotic ratio of RGD-KLA/PTX-Lips was the highest because of the mitochondria-targeted drug delivery and the activation of mitochondrial apoptosis pathways, as evidenced by visible mitochondrial localization, decreased mitochondrial membrane potential, release of cytochrome c and increased activities of caspase-9 and caspase-3. The strongest tumor growth inhibition (TGI; 80.6%) and antiangiogenesis effects without systemic toxicity were also observed in RGD-KLA/PTX-Lip-treated 4T1 tumor xenograft BALB/c mice. In conclusion, these multistage tumor-targeting liposomes represent a promising anticancer drug delivery system (DDS) capable of maximizing anticancer therapeutic efficacy and minimizing systemic toxicity. Keywords: multistage tumor-targeting liposome, mitochondria, paclitaxel, anticancer, antiangiogenesisSun JJiang LLin YGerhard EMJiang XLi LYang JGu ZDove Medical Pressarticlemultistage tumor-targeting liposomemitochondriapaclitaxel (PTX)anticanceranti-angiogenesisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1517-1537 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	multistage tumor-targeting liposome mitochondria paclitaxel (PTX) anticancer anti-angiogenesis Medicine (General) R5-920
spellingShingle	multistage tumor-targeting liposome mitochondria paclitaxel (PTX) anticancer anti-angiogenesis Medicine (General) R5-920 Sun J Jiang L Lin Y Gerhard EM Jiang X Li L Yang J Gu Z Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides
description	Jiawei Sun,1 Lei Jiang,2 Yi Lin,3 Ethan Michael Gerhard,4 Xuehua Jiang,1 Li Li,3 Jian Yang,4 Zhongwei Gu3 1West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu, 3National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Biomedical Engineering Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, USA Abstract: Mitochondria serve as both “energy factories” and “suicide weapon stores” of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy. Here, multistage tumor-targeting liposomes containing two targeted peptide-modified lipids, cRGD-PEG2000-DSPE and KLA-PEG2000-DSPE, were developed for encapsulation of the anticancer drug paclitaxel (PTX, RGD-KLA/PTX-Lips). Compared with Taxol (free PTX), RGD/PTX-Lips and KLA/PTX-Lips, the half-maximal inhibitory concentration (IC50) value of RGD-KLA/PTX-Lips in vitro was 1.9-, 36.7- and 22.7-fold lower with 4T1 cells, respectively, because of higher levels of cellular uptake. Similar results were also observed with human umbilical vascular endothelial cells (HUVECs). An apoptosis assay showed that the total apoptotic ratio of RGD-KLA/PTX-Lips was the highest because of the mitochondria-targeted drug delivery and the activation of mitochondrial apoptosis pathways, as evidenced by visible mitochondrial localization, decreased mitochondrial membrane potential, release of cytochrome c and increased activities of caspase-9 and caspase-3. The strongest tumor growth inhibition (TGI; 80.6%) and antiangiogenesis effects without systemic toxicity were also observed in RGD-KLA/PTX-Lip-treated 4T1 tumor xenograft BALB/c mice. In conclusion, these multistage tumor-targeting liposomes represent a promising anticancer drug delivery system (DDS) capable of maximizing anticancer therapeutic efficacy and minimizing systemic toxicity. Keywords: multistage tumor-targeting liposome, mitochondria, paclitaxel, anticancer, antiangiogenesis
format	article
author	Sun J Jiang L Lin Y Gerhard EM Jiang X Li L Yang J Gu Z
author_facet	Sun J Jiang L Lin Y Gerhard EM Jiang X Li L Yang J Gu Z
author_sort	Sun J
title	Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides
title_short	Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides
title_full	Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides
title_fullStr	Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides
title_full_unstemmed	Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides
title_sort	enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with rgd and kla peptides
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/1e046999938b4a6791bc72ee3e1e486f
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Enhanced anticancer efficacy of paclitaxel through multistage tumor-targeting liposomes modified with RGD and KLA peptides

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