Transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery

Ying Li,1,2 Meng Wang,1,2 Bu-Wei Huang,1,2 Yuan Ping,3 Jian You,1 Jian-Qing Gao1,2 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2Zhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Re...

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Autores principales:	Li Y, Wang M, Huang B, Ping Y, You J, Gao J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Liposomes Doxorubicin Cellular uptake Cell malignancy Transcriptional profiling Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/26056ef467624bcaab87b5f8a09063da
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spelling	oai:doaj.org-article:26056ef467624bcaab87b5f8a09063da2021-12-02T01:50:20ZTranscriptome-wide elucidation of liposomal formulations for anticancer drug delivery1178-2013https://doaj.org/article/26056ef467624bcaab87b5f8a09063da2017-11-01T00:00:00Zhttps://www.dovepress.com/transcriptome-wide-elucidation-of-liposomal-formulations-for-anticance-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ying Li,1,2 Meng Wang,1,2 Bu-Wei Huang,1,2 Yuan Ping,3 Jian You,1 Jian-Qing Gao1,2 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2Zhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 3School of Materials Science and Engineering, Nanyang Technological University, Singapore Abstract: Although widely used in chemotherapy, free doxorubicin (Dox) might enhance cell malignancy undesirably. Liposomal Dox (Doxlipo) has been clinically approved for the treatment of breast cancer due to reduced systematical toxicity and increased tumor targeting, yet the transcriptome-wide elucidation of the Doxlipo formulations remains elusive. To this end, we explored the impact of two Dox liposomal formulations, Doxlipo mainly containing hydrogenated soy phosphatidylcholine or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, on the transcriptional pattern of MCF-7 cells. The two types of Dox liposomal formulations with different drug release kinetics were investigated to reveal the relationship between the formulation and tumor malignancy. Interestingly, we found that liposomal formulation significantly altered the transcriptional pattern of a wide range of genes. Under equivalent dosage of Dox, free Dox substantially changed the expression of ANK1, ACTA2, GPR87, GDF15, FZD6, and WNT4 in MCF-7 cells. Notably, free Dox induced much higher expression of ABCB1 and significantly enhanced the cell migration behavior in comparison with HSPC Doxlipo under a similar level of cytotoxicity. Finally, siRNA targeting GPR87 was codelivered with cationic Doxlipo to reduce the expression of malignancy-related genes. Our study, for the first time, provides an overview of the influence of formulation on the malignancy at transcriptional level and reveals the relationship between cytotoxicity and cell malignancy from the formulation aspect, offering valuable reference for the future formulation design for anticancer drug delivery. Keywords: liposomes, doxorubicin, cellular uptake, cell malignancy, transcriptional profilingLi YWang MHuang BPing YYou JGao JDove Medical PressarticleLiposomesDoxorubicinCellular uptakeCell malignancyTranscriptional profilingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8557-8572 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Liposomes Doxorubicin Cellular uptake Cell malignancy Transcriptional profiling Medicine (General) R5-920
spellingShingle	Liposomes Doxorubicin Cellular uptake Cell malignancy Transcriptional profiling Medicine (General) R5-920 Li Y Wang M Huang B Ping Y You J Gao J Transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery
description	Ying Li,1,2 Meng Wang,1,2 Bu-Wei Huang,1,2 Yuan Ping,3 Jian You,1 Jian-Qing Gao1,2 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2Zhejiang Province Key Laboratory of Anticancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 3School of Materials Science and Engineering, Nanyang Technological University, Singapore Abstract: Although widely used in chemotherapy, free doxorubicin (Dox) might enhance cell malignancy undesirably. Liposomal Dox (Doxlipo) has been clinically approved for the treatment of breast cancer due to reduced systematical toxicity and increased tumor targeting, yet the transcriptome-wide elucidation of the Doxlipo formulations remains elusive. To this end, we explored the impact of two Dox liposomal formulations, Doxlipo mainly containing hydrogenated soy phosphatidylcholine or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, on the transcriptional pattern of MCF-7 cells. The two types of Dox liposomal formulations with different drug release kinetics were investigated to reveal the relationship between the formulation and tumor malignancy. Interestingly, we found that liposomal formulation significantly altered the transcriptional pattern of a wide range of genes. Under equivalent dosage of Dox, free Dox substantially changed the expression of ANK1, ACTA2, GPR87, GDF15, FZD6, and WNT4 in MCF-7 cells. Notably, free Dox induced much higher expression of ABCB1 and significantly enhanced the cell migration behavior in comparison with HSPC Doxlipo under a similar level of cytotoxicity. Finally, siRNA targeting GPR87 was codelivered with cationic Doxlipo to reduce the expression of malignancy-related genes. Our study, for the first time, provides an overview of the influence of formulation on the malignancy at transcriptional level and reveals the relationship between cytotoxicity and cell malignancy from the formulation aspect, offering valuable reference for the future formulation design for anticancer drug delivery. Keywords: liposomes, doxorubicin, cellular uptake, cell malignancy, transcriptional profiling
format	article
author	Li Y Wang M Huang B Ping Y You J Gao J
author_facet	Li Y Wang M Huang B Ping Y You J Gao J
author_sort	Li Y
title	Transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery
title_short	Transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery
title_full	Transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery
title_fullStr	Transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery
title_full_unstemmed	Transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery
title_sort	transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/26056ef467624bcaab87b5f8a09063da
work_keys_str_mv	AT liy transcriptomewideelucidationofliposomalformulationsforanticancerdrugdelivery AT wangm transcriptomewideelucidationofliposomalformulationsforanticancerdrugdelivery AT huangb transcriptomewideelucidationofliposomalformulationsforanticancerdrugdelivery AT pingy transcriptomewideelucidationofliposomalformulationsforanticancerdrugdelivery AT youj transcriptomewideelucidationofliposomalformulationsforanticancerdrugdelivery AT gaoj transcriptomewideelucidationofliposomalformulationsforanticancerdrugdelivery
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Transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery

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