Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer

Orleans Martey,1 Mhairi Nimick,1 Sebastien Taurin,1 Vignesh Sundararajan,1 Khaled Greish,2 Rhonda J Rosengren1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University...

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Autores principales:	Martey O, Nimick M, Taurin S, Sundararajan V, Greish K, Rosengren RJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	curcumin derivatives nanomedicine EGFR biodistribution Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/52525ea9c89243fd92664233c5016940
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spelling	oai:doaj.org-article:52525ea9c89243fd92664233c50169402021-12-02T04:57:47ZStyrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer1178-2013https://doaj.org/article/52525ea9c89243fd92664233c50169402017-10-01T00:00:00Zhttps://www.dovepress.com/styrene-maleic-acid-encapsulated-rl71-micelles-suppress-tumor-growth-i-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Orleans Martey,1 Mhairi Nimick,1 Sebastien Taurin,1 Vignesh Sundararajan,1 Khaled Greish,2 Rhonda J Rosengren1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Patients with triple negative breast cancer have a poor prognosis due in part to the lack of targeted therapies. In the search for novel drugs, our laboratory has developed a second-generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71), that exhibits potent in vitro cytotoxicity. To improve the clinical potential of this drug, we have encapsulated it in styrene maleic acid (SMA) micelles. SMA-RL71 showed improved biodistribution, and drug accumulation in the tumor increased 16-fold compared to control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks) also significantly suppressed tumor growth compared to control in a xenograft model of triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in apoptosis. The drug treatment also modulated various cell signaling proteins including the epidermal growth factor receptor, with the mechanisms for tumor suppression consistent with previous work with RL71 in vitro. The nanoformulation was also nontoxic as shown by normal levels of plasma markers for liver and kidney injury following weekly administration of SMA-RL71 (10 mg/kg) for 90 days. Thus, we report clinical potential following encapsulation of a novel curcumin derivative, RL71, in SMA micelles. Keywords: curcumin derivatives, nanomedicine, EGFR, biodistributionMartey ONimick MTaurin SSundararajan VGreish KRosengren RJDove Medical Pressarticlecurcumin derivativesnanomedicineEGFRbiodistributionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 7225-7237 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	curcumin derivatives nanomedicine EGFR biodistribution Medicine (General) R5-920
spellingShingle	curcumin derivatives nanomedicine EGFR biodistribution Medicine (General) R5-920 Martey O Nimick M Taurin S Sundararajan V Greish K Rosengren RJ Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer
description	Orleans Martey,1 Mhairi Nimick,1 Sebastien Taurin,1 Vignesh Sundararajan,1 Khaled Greish,2 Rhonda J Rosengren1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Patients with triple negative breast cancer have a poor prognosis due in part to the lack of targeted therapies. In the search for novel drugs, our laboratory has developed a second-generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71), that exhibits potent in vitro cytotoxicity. To improve the clinical potential of this drug, we have encapsulated it in styrene maleic acid (SMA) micelles. SMA-RL71 showed improved biodistribution, and drug accumulation in the tumor increased 16-fold compared to control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks) also significantly suppressed tumor growth compared to control in a xenograft model of triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in apoptosis. The drug treatment also modulated various cell signaling proteins including the epidermal growth factor receptor, with the mechanisms for tumor suppression consistent with previous work with RL71 in vitro. The nanoformulation was also nontoxic as shown by normal levels of plasma markers for liver and kidney injury following weekly administration of SMA-RL71 (10 mg/kg) for 90 days. Thus, we report clinical potential following encapsulation of a novel curcumin derivative, RL71, in SMA micelles. Keywords: curcumin derivatives, nanomedicine, EGFR, biodistribution
format	article
author	Martey O Nimick M Taurin S Sundararajan V Greish K Rosengren RJ
author_facet	Martey O Nimick M Taurin S Sundararajan V Greish K Rosengren RJ
author_sort	Martey O
title	Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer
title_short	Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer
title_full	Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer
title_fullStr	Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer
title_full_unstemmed	Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer
title_sort	styrene maleic acid-encapsulated rl71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/52525ea9c89243fd92664233c5016940
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Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer

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