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

Koloczek, P. ; Skórska-Stania, A. ; Cierniak, A. ; Sebastian, V. (Universidad de Zaragoza) ; Komarnicka, U.K. ; Plotek, M. ; Kyziol, A.

Resumen: 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.

Idioma: Inglés

DOI: 10.1016/j.ejpb.2018.04.016

Año: 2018

Publicado en: European Journal of Pharmaceutics and Biopharmaceutics 128 (2018), 69-81
ISSN: 0939-6411

Factor impacto JCR: 4.708 (2018)

Categ. JCR: PHARMACOLOGY & PHARMACY rank: 28 / 266 = 0.105 (2018) - Q1 - T1

Factor impacto SCIMAGO: 1.326 - Biotechnology (Q1) - Pharmaceutical Science (Q1) - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CIBER-BBN

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)