Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro

Abstract The heat shock protein 90 inhibitor, luminespib, has demonstrated potent preclinical activity against numerous cancers. However, clinical translation has been impeded by dose-limiting toxicities that have necessitated dosing schedules which have reduced therapeutic efficacy. As such, lumine...

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Autores principales:	Brittany Epp-Ducharme, Michael Dunne, Linyu Fan, James C. Evans, Lubabah Ahmed, Pauric Bannigan, Christine Allen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/32a868415be64939b8264f6b7ef89b9c
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spelling	oai:doaj.org-article:32a868415be64939b8264f6b7ef89b9c2021-12-02T15:49:53ZHeat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro10.1038/s41598-021-90585-w2045-2322https://doaj.org/article/32a868415be64939b8264f6b7ef89b9c2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90585-whttps://doaj.org/toc/2045-2322Abstract The heat shock protein 90 inhibitor, luminespib, has demonstrated potent preclinical activity against numerous cancers. However, clinical translation has been impeded by dose-limiting toxicities that have necessitated dosing schedules which have reduced therapeutic efficacy. As such, luminespib is a prime candidate for reformulation using advanced drug delivery strategies that improve tumor delivery efficiency and limit off-target side effects. Specifically, thermosensitive liposomes are proposed as a drug delivery strategy capable of delivering high concentrations of drug to the tumor in combination with other chemotherapeutic molecules. Indeed, this work establishes that luminespib exhibits synergistic activity in lung cancer in combination with standard of care drugs such as cisplatin and vinorelbine. While our research team has previously developed thermosensitive liposomes containing cisplatin or vinorelbine, this work presents the first liposomal formulation of luminespib. The physico-chemical properties and heat-triggered release of the formulation were characterized. Cytotoxicity assays were used to determine the optimal drug ratios for treatment of luminespib in combination with cisplatin or vinorelbine in non-small cell lung cancer cells. The formulation and drug combination work presented in this paper offer the potential for resuscitation of the clinical prospects of a promising anticancer agent.Brittany Epp-DucharmeMichael DunneLinyu FanJames C. EvansLubabah AhmedPauric BanniganChristine AllenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brittany Epp-Ducharme Michael Dunne Linyu Fan James C. Evans Lubabah Ahmed Pauric Bannigan Christine Allen Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro
description	Abstract The heat shock protein 90 inhibitor, luminespib, has demonstrated potent preclinical activity against numerous cancers. However, clinical translation has been impeded by dose-limiting toxicities that have necessitated dosing schedules which have reduced therapeutic efficacy. As such, luminespib is a prime candidate for reformulation using advanced drug delivery strategies that improve tumor delivery efficiency and limit off-target side effects. Specifically, thermosensitive liposomes are proposed as a drug delivery strategy capable of delivering high concentrations of drug to the tumor in combination with other chemotherapeutic molecules. Indeed, this work establishes that luminespib exhibits synergistic activity in lung cancer in combination with standard of care drugs such as cisplatin and vinorelbine. While our research team has previously developed thermosensitive liposomes containing cisplatin or vinorelbine, this work presents the first liposomal formulation of luminespib. The physico-chemical properties and heat-triggered release of the formulation were characterized. Cytotoxicity assays were used to determine the optimal drug ratios for treatment of luminespib in combination with cisplatin or vinorelbine in non-small cell lung cancer cells. The formulation and drug combination work presented in this paper offer the potential for resuscitation of the clinical prospects of a promising anticancer agent.
format	article
author	Brittany Epp-Ducharme Michael Dunne Linyu Fan James C. Evans Lubabah Ahmed Pauric Bannigan Christine Allen
author_facet	Brittany Epp-Ducharme Michael Dunne Linyu Fan James C. Evans Lubabah Ahmed Pauric Bannigan Christine Allen
author_sort	Brittany Epp-Ducharme
title	Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro
title_short	Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro
title_full	Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro
title_fullStr	Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro
title_full_unstemmed	Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro
title_sort	heat-activated nanomedicine formulation improves the anticancer potential of the hsp90 inhibitor luminespib in vitro
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/32a868415be64939b8264f6b7ef89b9c
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Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro

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