GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers

Wei-Wei Xu,1,* Da-yu Liu,2,* Ying-chun Cao,1 Xiang-yun Wang1 1Department of Ear-Nose-Throat, Dongying People’s Hospital, Dongying, 2ENT & HN Surgery Department, Qilu Hospital, Shandong University, Jinan, Shandong, China *These authors contributed equally to this work Abstract: I...

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Autores principales:	Xu WW, Liu D, Cao Y, Wang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Laryngeal cancer docetaxel siRNA anticancer effect therapeutic efficacy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/86f3bbbe9f6b471ea39d86d740eecbbf
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spelling	oai:doaj.org-article:86f3bbbe9f6b471ea39d86d740eecbbf2021-12-02T05:02:59ZGE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers1178-2013https://doaj.org/article/86f3bbbe9f6b471ea39d86d740eecbbf2017-09-01T00:00:00Zhttps://www.dovepress.com/ge11-peptide-conjugated-nanoliposomes-to-enhance-the-combinational-the-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wei-Wei Xu,1,* Da-yu Liu,2,* Ying-chun Cao,1 Xiang-yun Wang1 1Department of Ear-Nose-Throat, Dongying People’s Hospital, Dongying, 2ENT & HN Surgery Department, Qilu Hospital, Shandong University, Jinan, Shandong, China *These authors contributed equally to this work Abstract: In this study, dual therapeutic-loaded GE11 peptide-conjugated liposomes were developed and applied to enhance therapeutic efficacies of standard-of-care regimens for the treatment of laryngeal cancer. The therapeutic strategy used here was a combination treatment with the chemotherapeutic docetaxel (DTX) and siRNA against the ABCG2 gene that regulates multidrug resistance in many tumor types. Liposome-encapsulated DTX/ABCG2–siRNA molecules were targeted to recognize tumor cells of squamous morphology by conjugation to the EGFR-targeting ligand, GE11. Targeted, drug-infused liposomes were nanosized and exhibited controlled release of DTX. Presence of GE11 peptides on liposomal surfaces enhanced the quantities of liposomal constructs taken up by Hep-2 laryngeal cancer cells. GE11 peptide-conjugated liposomes also enhanced cytotoxic effects against Hep-2 laryngeal cancer cells when compared to treatment with free DTX, thereby reducing IC50 values. Additionally, GE11 peptide-conjugated liposomes had significantly increased anti-tumor and apoptotic effects. Treatments with the GDSL nanoparticle formulation inhibited tumor growth in Hep-2 xenograft-bearing nude mouse models when compared to treatments with non-targeted NP constructs. Treatment of the mouse models with GE11 peptide-conjugated liposomes mitigated toxicities observed after treatment with free DTX. Taken together, liposomal encapsulation of DTX and ABCG2–siRNA improved the anti-tumor effects of treatment with free DTX in Hep-2 cell lines, and conjugation of GE11 peptides to liposomal constructs enhanced anti-tumor efficacies and specificities in laryngeal cancer cells. Keywords: laryngeal cancer, docetaxel, ABCG2–siRNA, anti-tumor efficacy, liposomal chemotherapy carriers, GE11 peptide-targeted liposomesXu WWLiu DCao YWang XDove Medical PressarticleLaryngeal cancerdocetaxelsiRNAanticancer effecttherapeutic efficacyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6461-6470 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Laryngeal cancer docetaxel siRNA anticancer effect therapeutic efficacy Medicine (General) R5-920
spellingShingle	Laryngeal cancer docetaxel siRNA anticancer effect therapeutic efficacy Medicine (General) R5-920 Xu WW Liu D Cao Y Wang X GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers
description	Wei-Wei Xu,1,* Da-yu Liu,2,* Ying-chun Cao,1 Xiang-yun Wang1 1Department of Ear-Nose-Throat, Dongying People’s Hospital, Dongying, 2ENT & HN Surgery Department, Qilu Hospital, Shandong University, Jinan, Shandong, China *These authors contributed equally to this work Abstract: In this study, dual therapeutic-loaded GE11 peptide-conjugated liposomes were developed and applied to enhance therapeutic efficacies of standard-of-care regimens for the treatment of laryngeal cancer. The therapeutic strategy used here was a combination treatment with the chemotherapeutic docetaxel (DTX) and siRNA against the ABCG2 gene that regulates multidrug resistance in many tumor types. Liposome-encapsulated DTX/ABCG2–siRNA molecules were targeted to recognize tumor cells of squamous morphology by conjugation to the EGFR-targeting ligand, GE11. Targeted, drug-infused liposomes were nanosized and exhibited controlled release of DTX. Presence of GE11 peptides on liposomal surfaces enhanced the quantities of liposomal constructs taken up by Hep-2 laryngeal cancer cells. GE11 peptide-conjugated liposomes also enhanced cytotoxic effects against Hep-2 laryngeal cancer cells when compared to treatment with free DTX, thereby reducing IC50 values. Additionally, GE11 peptide-conjugated liposomes had significantly increased anti-tumor and apoptotic effects. Treatments with the GDSL nanoparticle formulation inhibited tumor growth in Hep-2 xenograft-bearing nude mouse models when compared to treatments with non-targeted NP constructs. Treatment of the mouse models with GE11 peptide-conjugated liposomes mitigated toxicities observed after treatment with free DTX. Taken together, liposomal encapsulation of DTX and ABCG2–siRNA improved the anti-tumor effects of treatment with free DTX in Hep-2 cell lines, and conjugation of GE11 peptides to liposomal constructs enhanced anti-tumor efficacies and specificities in laryngeal cancer cells. Keywords: laryngeal cancer, docetaxel, ABCG2–siRNA, anti-tumor efficacy, liposomal chemotherapy carriers, GE11 peptide-targeted liposomes
format	article
author	Xu WW Liu D Cao Y Wang X
author_facet	Xu WW Liu D Cao Y Wang X
author_sort	Xu WW
title	GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers
title_short	GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers
title_full	GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers
title_fullStr	GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers
title_full_unstemmed	GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers
title_sort	ge11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and sirna in laryngeal cancers
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/86f3bbbe9f6b471ea39d86d740eecbbf
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GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers

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