Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment

Novel half-sandwich ruthenium(II) complexes with aminomethyl(diphenyl)phosphine derived from fluoroloquinolones (RuPCp, RuPSf, RuPLm, RuPNr) were being investigated as alternatives to well-established metal-based chemotherapeutics. All compounds were characterized by elemental analysis, selected spe...

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Autores: Kołoczek, Przemysław, Skórska-Stania, Agnieszka, Cierniak, Agnieszka, Sebastián, Víctor, Komarnicka, Urszula K., Płotek, Michał, Kyzioł, Agnieszka
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/368850
Acceso en línea:http://hdl.handle.net/10261/368850
Access Level:acceso abierto
Palabra clave:Arene ruthenium(II) complexes
Fluoroquinolones
Polymeric micelles
Drug delivery
Anticancer activity
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spelling Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatmentKołoczek, PrzemysławSkórska-Stania, AgnieszkaCierniak, AgnieszkaSebastián, VíctorKomarnicka, Urszula K.Płotek, MichałKyzioł, AgnieszkaArene ruthenium(II) complexesFluoroquinolonesPolymeric micellesDrug deliveryAnticancer activityNovel half-sandwich ruthenium(II) complexes with aminomethyl(diphenyl)phosphine derived from fluoroloquinolones (RuPCp, RuPSf, RuPLm, RuPNr) were being investigated as alternatives to well-established metal-based chemotherapeutics. All compounds were characterized by elemental analysis, selected spectroscopic methods (i.e., absorption and fluorescence spectroscopies, ESI-MS, NMR, circular dichroizm), X-ray diffractometry, ICP-MS, and electrochemical techniques. To overcome low solubility, serious side effects connected with systemic cytotoxicity of ruthenium complexes, and acquiring the resistance of cancer cells, polymeric nanoformulations based on Pluronic P-123 micelles loaded with selected Ru(II) complexes were prepared and characterized. Resulting micelles (RuPCp_M, RuPNr_M) enabled efficient drug accumulation inside human lung adenocarcinoma (A549 tumor cell line), proved by confocal microscopy and ICP-MS analysis, allowing cytotoxic action. Studied complexes exhibited promising cytotoxicity in vitro with IC50 values significantly lower than the reference drug – cisplatin. The fluorescence spectroscopic data (CT-DNA titration, in vitro cell staining) together with analysis of DNA fragmentation (pBR322 plasmid, comet assay) provided clear evidence for the interaction with DNA inducing apoptotic cell death.The research was carried out with the equipment purchased thanks to the financial support of the European Regional Development Fund in the Framework of the Polish Innovation Economy Operational Program (contract no. POIG.02.01.00-12-023/08). The authors gratefully acknowledge financial support from the Polish National Science Centre (Grant 2011/03/B/ST5/01557). Electrochemical characterization of studied complexes were carried out thanks to the financial support from the Polish National Science Centre (Grant 2017/01/X/NZ7/01148). The authors are grateful to Marcin Kobielusz, PhD, from Jagiellonian University in Kraków for helpful and comprehensive discussions on electrochemical characterization of studied complexes. The authors would like also to acknowledge Professor Mariusz Kępczyński from Jagiellonian University in Kraków for confocal imaging. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011 financed by the Instituto de Salud Carlos III with the assistance of the European Regional Development Fund.Peer reviewedElsevierEuropean CommissionNational Science Centre (Poland)Jagiellonian University in KrakówInstituto de Salud Carlos III202420242018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://hdl.handle.net/10261/368850reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1016/j.ejpb.2018.04.016https://doi.org/10.1016/j.ejpb.2018.04.016Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3688502026-05-22T06:33:51Z
dc.title.none.fl_str_mv Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment
title Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment
spellingShingle Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment
Kołoczek, Przemysław
Arene ruthenium(II) complexes
Fluoroquinolones
Polymeric micelles
Drug delivery
Anticancer activity
title_short Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment
title_full Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment
title_fullStr Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment
title_full_unstemmed Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment
title_sort Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment
dc.creator.none.fl_str_mv Kołoczek, Przemysław
Skórska-Stania, Agnieszka
Cierniak, Agnieszka
Sebastián, Víctor
Komarnicka, Urszula K.
Płotek, Michał
Kyzioł, Agnieszka
author Kołoczek, Przemysław
author_facet Kołoczek, Przemysław
Skórska-Stania, Agnieszka
Cierniak, Agnieszka
Sebastián, Víctor
Komarnicka, Urszula K.
Płotek, Michał
Kyzioł, Agnieszka
author_role author
author2 Skórska-Stania, Agnieszka
Cierniak, Agnieszka
Sebastián, Víctor
Komarnicka, Urszula K.
Płotek, Michał
Kyzioł, Agnieszka
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
National Science Centre (Poland)
Jagiellonian University in Kraków
Instituto de Salud Carlos III
dc.subject.none.fl_str_mv Arene ruthenium(II) complexes
Fluoroquinolones
Polymeric micelles
Drug delivery
Anticancer activity
topic Arene ruthenium(II) complexes
Fluoroquinolones
Polymeric micelles
Drug delivery
Anticancer activity
description Novel half-sandwich ruthenium(II) complexes with aminomethyl(diphenyl)phosphine derived from fluoroloquinolones (RuPCp, RuPSf, RuPLm, RuPNr) were being investigated as alternatives to well-established metal-based chemotherapeutics. All compounds were characterized by elemental analysis, selected spectroscopic methods (i.e., absorption and fluorescence spectroscopies, ESI-MS, NMR, circular dichroizm), X-ray diffractometry, ICP-MS, and electrochemical techniques. To overcome low solubility, serious side effects connected with systemic cytotoxicity of ruthenium complexes, and acquiring the resistance of cancer cells, polymeric nanoformulations based on Pluronic P-123 micelles loaded with selected Ru(II) complexes were prepared and characterized. Resulting micelles (RuPCp_M, RuPNr_M) enabled efficient drug accumulation inside human lung adenocarcinoma (A549 tumor cell line), proved by confocal microscopy and ICP-MS analysis, allowing cytotoxic action. Studied complexes exhibited promising cytotoxicity in vitro with IC50 values significantly lower than the reference drug – cisplatin. The fluorescence spectroscopic data (CT-DNA titration, in vitro cell staining) together with analysis of DNA fragmentation (pBR322 plasmid, comet assay) provided clear evidence for the interaction with DNA inducing apoptotic cell death.
publishDate 2018
dc.date.none.fl_str_mv 2018
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/368850
url http://hdl.handle.net/10261/368850
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1016/j.ejpb.2018.04.016
https://doi.org/10.1016/j.ejpb.2018.04.016
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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