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...
| Autores: | , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versión aceptada para publicación |
| Data de publicação: | 2018 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositório: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/368850 |
| Acesso em linha: | http://hdl.handle.net/10261/368850 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Arene ruthenium(II) complexes Fluoroquinolones Polymeric micelles Drug delivery Anticancer activity |
| Resumo: | 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. |
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