GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation

Liang Cheng,1,* Fa-Zhen Huang,1,2,* Li-Fang Cheng,1 Ya-Qin Zhu,1 Qing Hu,1 Ling Li,1 Lin Wei1, Da-Wei Chen1 1Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu Province, 2Department of Pharmacy, Central Hospital of Zaozhuang Minging Group, Zaozhuang,...

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Autores principales:	Cheng L, Huang FZ, Cheng LF, Zhu YQ, Hu Q, Li L, Wei L, Chen DW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/66e3f37e2ae54fd99bfa1a09aa281343
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spelling	oai:doaj.org-article:66e3f37e2ae54fd99bfa1a09aa2813432021-12-02T02:39:45ZGE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation1178-2013https://doaj.org/article/66e3f37e2ae54fd99bfa1a09aa2813432014-02-01T00:00:00Zhttp://www.dovepress.com/ge11-modified-liposomes-for-non-small-cell-lung-cancer-targeting-prepa-a15783https://doaj.org/toc/1178-2013 Liang Cheng,1,* Fa-Zhen Huang,1,2,* Li-Fang Cheng,1 Ya-Qin Zhu,1 Qing Hu,1 Ling Li,1 Lin Wei1, Da-Wei Chen1 1Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu Province, 2Department of Pharmacy, Central Hospital of Zaozhuang Minging Group, Zaozhuang, Shandong Province, People's Republic of China *These authors contributed equally to this work Abstract: Non-small cell lung cancer (NSCLC) is a serious threat to human health, and 40%–80% of NSCLCs express high levels of epidermal growth factor receptor (EGFR). GE11 is a novel peptide and exhibits high affinity for EGFR binding. The aim of this study was to construct and evaluate GE11-modified liposomes for targeted drug delivery to EGFR-positive NSCLC. Doxorubicin, a broad-spectrum antitumor agent, was chosen as the payload. GE11 was conjugated to the distal end of DSPE-PEG2000-Mal by an addition reaction with a conjugation efficiency above 90%. Doxorubicin-loaded liposomes containing GE11 (GE11-LP/DOX) at densities ranging from 0% to 15% were prepared by combination of a thin film hydration method and a post insertion method. Irrespective of GE11 density, the physicochemical properties of these targeted liposomes, including particle size, zeta potential, and drug entrapment efficiency, were nearly identical. Interestingly, the cytotoxic effect of the liposomes on A549 tumor cells was closely related to GE11 density, and liposomes with 10% GE11 had the highest tumor cell killing activity and a 2.6-fold lower half maximal inhibitory concentration than that of the nontargeted counterpart (PEG-LP/DOX). Fluorescence microscopy and flow cytometry analysis revealed that GE11 significantly increased cellular uptake of the liposomes, which could be ascribed to specific EGFR-mediated endocytosis. It was found that multiple endocytic pathways were involved in entry of GE11-LP/DOX into cells, but GE11 assisted in cellular internalization mainly via the clathrin-mediated endocytosis pathway. Importantly, the GE11-modified liposomes showed enhanced accumulation and prolonged retention in tumor tissue, as evidenced by a 2.2-fold stronger mean fluorescence intensity in tumor tissue than the unmodified liposomes at 24 hours. In summary, GE11-modified liposomes may be a promising platform for targeted delivery of chemotherapeutic drugs in NSCLC. Keywords: epidermal growth factor receptor, nanosized carrier, targeted drug delivery, cellular uptake mechanism, in vivo imagingCheng LHuang FZCheng LFZhu YQHu QLi LWei LChen DWDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 921-935 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Cheng L Huang FZ Cheng LF Zhu YQ Hu Q Li L Wei L Chen DW GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation
description	Liang Cheng,1,* Fa-Zhen Huang,1,2,* Li-Fang Cheng,1 Ya-Qin Zhu,1 Qing Hu,1 Ling Li,1 Lin Wei1, Da-Wei Chen1 1Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu Province, 2Department of Pharmacy, Central Hospital of Zaozhuang Minging Group, Zaozhuang, Shandong Province, People's Republic of China *These authors contributed equally to this work Abstract: Non-small cell lung cancer (NSCLC) is a serious threat to human health, and 40%–80% of NSCLCs express high levels of epidermal growth factor receptor (EGFR). GE11 is a novel peptide and exhibits high affinity for EGFR binding. The aim of this study was to construct and evaluate GE11-modified liposomes for targeted drug delivery to EGFR-positive NSCLC. Doxorubicin, a broad-spectrum antitumor agent, was chosen as the payload. GE11 was conjugated to the distal end of DSPE-PEG2000-Mal by an addition reaction with a conjugation efficiency above 90%. Doxorubicin-loaded liposomes containing GE11 (GE11-LP/DOX) at densities ranging from 0% to 15% were prepared by combination of a thin film hydration method and a post insertion method. Irrespective of GE11 density, the physicochemical properties of these targeted liposomes, including particle size, zeta potential, and drug entrapment efficiency, were nearly identical. Interestingly, the cytotoxic effect of the liposomes on A549 tumor cells was closely related to GE11 density, and liposomes with 10% GE11 had the highest tumor cell killing activity and a 2.6-fold lower half maximal inhibitory concentration than that of the nontargeted counterpart (PEG-LP/DOX). Fluorescence microscopy and flow cytometry analysis revealed that GE11 significantly increased cellular uptake of the liposomes, which could be ascribed to specific EGFR-mediated endocytosis. It was found that multiple endocytic pathways were involved in entry of GE11-LP/DOX into cells, but GE11 assisted in cellular internalization mainly via the clathrin-mediated endocytosis pathway. Importantly, the GE11-modified liposomes showed enhanced accumulation and prolonged retention in tumor tissue, as evidenced by a 2.2-fold stronger mean fluorescence intensity in tumor tissue than the unmodified liposomes at 24 hours. In summary, GE11-modified liposomes may be a promising platform for targeted delivery of chemotherapeutic drugs in NSCLC. Keywords: epidermal growth factor receptor, nanosized carrier, targeted drug delivery, cellular uptake mechanism, in vivo imaging
format	article
author	Cheng L Huang FZ Cheng LF Zhu YQ Hu Q Li L Wei L Chen DW
author_facet	Cheng L Huang FZ Cheng LF Zhu YQ Hu Q Li L Wei L Chen DW
author_sort	Cheng L
title	GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation
title_short	GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation
title_full	GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation
title_fullStr	GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation
title_full_unstemmed	GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation
title_sort	ge11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/66e3f37e2ae54fd99bfa1a09aa281343
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GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation

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