Liposomal Binuclear Ir(III)-Cu(II) Coordination Compounds with Phosphino-Fluoroquinolone Conjugates for Human Prostate Carcinoma Treatment

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73616100" target="_blank" >RIV/61989592:15310/22:73616100 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/pdf/10.1021/acs.inorgchem.2c03015" target="_blank" >https://pubs.acs.org/doi/pdf/10.1021/acs.inorgchem.2c03015</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.inorgchem.2c03015" target="_blank" >10.1021/acs.inorgchem.2c03015</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Liposomal Binuclear Ir(III)-Cu(II) Coordination Compounds with Phosphino-Fluoroquinolone Conjugates for Human Prostate Carcinoma Treatment

Popis výsledku v původním jazyce

Novel heteronuclear Ir-III-Cu-II coordination compounds ([Ir(eta(5)-Cp*)Cl(2)Pcfx-Cu(phen)](NO3)center dot 1.75(CH3OH)center dot 0.75(H2O) (1), [Ir(eta(5)-Cp*)Cl(2)PnfxCu(phen)](NO3)center dot 1.75(CH3OH)center dot 0.75(H2O) (2), [Ir(eta(5)-Cp*)Cl(2)Plfx-Cu(phen)](NO3)center dot 1.3(H2O)center dot 1.95(CH3OH) (3), [Ir(eta(5)-Cp*)Cl(2)Psfx-Cu(phen)] (4)) bearing phosphines derived from fluoroquinolones, namely, sparfloxacin (Hsfx), ciprofloxacin (Hcfx), lomefloxacin (Hlfx), and norfloxacin (Hnfx), have been synthesized and studied as possible anticancer chemotherapeutics. All compounds have been characterized by electrospray ionization mass spectrometry (ESI-MS), a number of spectroscopic methods (i.e., IR, fluorescence, and electron paramagnetic resonance (EPR)), cyclic voltammetry, variable-temperature magnetic susceptibility measurements, and X-ray diffractometry. The coordination geometry of IrIII in all complexes adopts a characteristic piano-stool geometry with the eta(5)-coordinated and three additional sites occupied by two chloride and phosphine ligands, while CuII ions in complexes 1 and 2 form a distorted square-pyramidal coordination geometry, and in complex 3, the coordination geometry around CuII ions is a distorted octahedron. Interestingly, the crystal structure of [Ir(eta(5)-Cp*)Cl(2)Plfx-Cu(phen)] features the one-dimensional (1D) metal-organic polymer. Liposomes loaded with redox-active and fluorescent [Ir(eta(5)-Cp*)Cl(2)Pcfx-Cu(phen)] (1L) have been prepared to increase water solubility and minimize serious systemic side effects. It has been proven, by confocal microscopy and an inductively coupled plasma mass spectrometry (ICP-MS) analysis, that the liposomal form of compound 1 can be effectively accumulated inside human lung adenocarcinoma and human prostate carcinoma cells with selective localization in nuclei. A cytometric analysis showed dominance of apoptosis over the other cell death types. Furthermore, the investigated nanoformulations induced changes in the cell cycle, leading to S phase arrest in a dose-dependent manner. Importantly, in vitro anticancer action on three-dimensional (3D) multicellular tumor spheroids has been demonstrated.

Název v anglickém jazyce

Liposomal Binuclear Ir(III)-Cu(II) Coordination Compounds with Phosphino-Fluoroquinolone Conjugates for Human Prostate Carcinoma Treatment

Popis výsledku anglicky

Novel heteronuclear Ir-III-Cu-II coordination compounds ([Ir(eta(5)-Cp*)Cl(2)Pcfx-Cu(phen)](NO3)center dot 1.75(CH3OH)center dot 0.75(H2O) (1), [Ir(eta(5)-Cp*)Cl(2)PnfxCu(phen)](NO3)center dot 1.75(CH3OH)center dot 0.75(H2O) (2), [Ir(eta(5)-Cp*)Cl(2)Plfx-Cu(phen)](NO3)center dot 1.3(H2O)center dot 1.95(CH3OH) (3), [Ir(eta(5)-Cp*)Cl(2)Psfx-Cu(phen)] (4)) bearing phosphines derived from fluoroquinolones, namely, sparfloxacin (Hsfx), ciprofloxacin (Hcfx), lomefloxacin (Hlfx), and norfloxacin (Hnfx), have been synthesized and studied as possible anticancer chemotherapeutics. All compounds have been characterized by electrospray ionization mass spectrometry (ESI-MS), a number of spectroscopic methods (i.e., IR, fluorescence, and electron paramagnetic resonance (EPR)), cyclic voltammetry, variable-temperature magnetic susceptibility measurements, and X-ray diffractometry. The coordination geometry of IrIII in all complexes adopts a characteristic piano-stool geometry with the eta(5)-coordinated and three additional sites occupied by two chloride and phosphine ligands, while CuII ions in complexes 1 and 2 form a distorted square-pyramidal coordination geometry, and in complex 3, the coordination geometry around CuII ions is a distorted octahedron. Interestingly, the crystal structure of [Ir(eta(5)-Cp*)Cl(2)Plfx-Cu(phen)] features the one-dimensional (1D) metal-organic polymer. Liposomes loaded with redox-active and fluorescent [Ir(eta(5)-Cp*)Cl(2)Pcfx-Cu(phen)] (1L) have been prepared to increase water solubility and minimize serious systemic side effects. It has been proven, by confocal microscopy and an inductively coupled plasma mass spectrometry (ICP-MS) analysis, that the liposomal form of compound 1 can be effectively accumulated inside human lung adenocarcinoma and human prostate carcinoma cells with selective localization in nuclei. A cytometric analysis showed dominance of apoptosis over the other cell death types. Furthermore, the investigated nanoformulations induced changes in the cell cycle, leading to S phase arrest in a dose-dependent manner. Importantly, in vitro anticancer action on three-dimensional (3D) multicellular tumor spheroids has been demonstrated.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

INORGANIC CHEMISTRY

ISSN

0020-1669

e-ISSN

1520-510X

Svazek periodika

61

Číslo periodika v rámci svazku

48

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

19261-19273

Kód UT WoS článku

000886622800001

EID výsledku v databázi Scopus

2-s2.0-85142446958