Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy

Han Liao,1,2 Shan Zhao,1,2 Huihui Wang,1,2 Yang Liu,1 Ying Zhang,1 Guangwei Sun1 1Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People’s Republic of China; 2University of Chinese Academy of Sciences,...

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Autores principales:	Liao H, Zhao S, Wang H, Liu Y, Zhang Y, Sun G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	nano-drugs self-assembly retinoid cancer therapy melanoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e74ec2d98542403b845d1961fe4a01ff
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spelling	oai:doaj.org-article:e74ec2d98542403b845d1961fe4a01ff2021-12-02T05:31:54ZSelf-Assembly Of Retinoid Nanoparticles For Melanoma Therapy1178-2013https://doaj.org/article/e74ec2d98542403b845d1961fe4a01ff2019-10-01T00:00:00Zhttps://www.dovepress.com/self-assembly-of-retinoid-nanoparticles-for-melanoma-therapy-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Han Liao,1,2 Shan Zhao,1,2 Huihui Wang,1,2 Yang Liu,1 Ying Zhang,1 Guangwei Sun1 1Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of ChinaCorrespondence: Guangwei SunScientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, People’s Republic of ChinaTel/Fax +86-411-82463027Email sungw@dicp.ac.cnBackground: Amphiphilic fusion drugs are covalent conjugates of a lipophilic drug and a hydrophilic drug or their active fragments. These carrier-free self-assembly nanomaterials are helpful to co-deliver two synergic drugs to the same site regardless of pharmacokinetic properties of individual drugs. Retinoic hydroxamic acid (RHA) is a “fusion drug” of all-trans retinoic acid (ATRA) and vorinostat, a histone deacetylase (HDAC) inhibitor showing synergic effect with ATRA on cancer therapy. Although RHA was synthesized in 2005, its nanoscale self-assembly property, anticancer activity, and possible related mechanism are still unclear.Methods: RHA nanoparticles were observed under transmission electron microscope (TEM). Both in vitro cell viability, colony formation assay, and in vivo xenograft mouse tumor model were employed here to study anticancer activity of RHA nanoparticles. The putative synergic anticancer mechanism of activating retinoic acid receptor (RAR) and inhibiting HDAC were investigated via receptor inhibitor rescue assay and in vitro enzyme activity assay, respectively.Results: RHA could form nanoparticle formation by self-assembly and abrogates growth of several solid tumor cell lines even after RHA nanoparticles’ washout. However, opposite to our initial hypothesis, pre-treating the melanoma cells with RAR antagonists showed no impact on inhibitory effect of RHA nanoparticles, which suggested that the target of the molecule on melanoma cells is not RAR and retinoid X receptor (RXR). Importantly, RHA nanoparticles inhibited the growth of xenograft tumors without obvious impact on haematological indexes and hepatorenal function of these tumor-bearing mice.Conclusion: Our findings demonstrate the promise of RHA nanoparticles in treating malignant melanoma tumors with high efficacy and low toxicity.Keywords: nano-drugs, self-assembly, retinoid, cancer therapy, melanomaLiao HZhao SWang HLiu YZhang YSun GDove Medical Pressarticlenano-drugsself-assemblyretinoidcancer therapymelanomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 7963-7973 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	nano-drugs self-assembly retinoid cancer therapy melanoma Medicine (General) R5-920
spellingShingle	nano-drugs self-assembly retinoid cancer therapy melanoma Medicine (General) R5-920 Liao H Zhao S Wang H Liu Y Zhang Y Sun G Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy
description	Han Liao,1,2 Shan Zhao,1,2 Huihui Wang,1,2 Yang Liu,1 Ying Zhang,1 Guangwei Sun1 1Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of ChinaCorrespondence: Guangwei SunScientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, People’s Republic of ChinaTel/Fax +86-411-82463027Email sungw@dicp.ac.cnBackground: Amphiphilic fusion drugs are covalent conjugates of a lipophilic drug and a hydrophilic drug or their active fragments. These carrier-free self-assembly nanomaterials are helpful to co-deliver two synergic drugs to the same site regardless of pharmacokinetic properties of individual drugs. Retinoic hydroxamic acid (RHA) is a “fusion drug” of all-trans retinoic acid (ATRA) and vorinostat, a histone deacetylase (HDAC) inhibitor showing synergic effect with ATRA on cancer therapy. Although RHA was synthesized in 2005, its nanoscale self-assembly property, anticancer activity, and possible related mechanism are still unclear.Methods: RHA nanoparticles were observed under transmission electron microscope (TEM). Both in vitro cell viability, colony formation assay, and in vivo xenograft mouse tumor model were employed here to study anticancer activity of RHA nanoparticles. The putative synergic anticancer mechanism of activating retinoic acid receptor (RAR) and inhibiting HDAC were investigated via receptor inhibitor rescue assay and in vitro enzyme activity assay, respectively.Results: RHA could form nanoparticle formation by self-assembly and abrogates growth of several solid tumor cell lines even after RHA nanoparticles’ washout. However, opposite to our initial hypothesis, pre-treating the melanoma cells with RAR antagonists showed no impact on inhibitory effect of RHA nanoparticles, which suggested that the target of the molecule on melanoma cells is not RAR and retinoid X receptor (RXR). Importantly, RHA nanoparticles inhibited the growth of xenograft tumors without obvious impact on haematological indexes and hepatorenal function of these tumor-bearing mice.Conclusion: Our findings demonstrate the promise of RHA nanoparticles in treating malignant melanoma tumors with high efficacy and low toxicity.Keywords: nano-drugs, self-assembly, retinoid, cancer therapy, melanoma
format	article
author	Liao H Zhao S Wang H Liu Y Zhang Y Sun G
author_facet	Liao H Zhao S Wang H Liu Y Zhang Y Sun G
author_sort	Liao H
title	Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy
title_short	Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy
title_full	Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy
title_fullStr	Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy
title_full_unstemmed	Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy
title_sort	self-assembly of retinoid nanoparticles for melanoma therapy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/e74ec2d98542403b845d1961fe4a01ff
work_keys_str_mv	AT liaoh selfassemblyofretinoidnanoparticlesformelanomatherapy AT zhaos selfassemblyofretinoidnanoparticlesformelanomatherapy AT wangh selfassemblyofretinoidnanoparticlesformelanomatherapy AT liuy selfassemblyofretinoidnanoparticlesformelanomatherapy AT zhangy selfassemblyofretinoidnanoparticlesformelanomatherapy AT sung selfassemblyofretinoidnanoparticlesformelanomatherapy
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Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy

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