title: Anticancer cationic ruthenium nanovectors: from rational molecular design to cellular uptake and bioactivity.
abstract: An efficient drug delivery strategy is presented for novel anticancer amphiphilic ruthenium anionic complexes, based on the formation of stable nanoparticles with the cationic lipid 1,2-dioleyl-3-trimethylammoniumpropane chloride (DOTAP). This strategy is aimed at ensuring high ruthenium content within the formulation, long half-life in physiological media, and enhanced cell uptake. An in-depth microstructural characterization of the aggregates obtained mixing the ruthenium complex and the phospholipid carrier at 50/50 molar ratio is realized by combining a variety of techniques, including dynamic light scattering (DLS), small angle neutron scattering (SANS), neutron reflectivity (NR), electron paramagnetic resonance (EPR), and zeta potential measurements. The in vitro bioactivity profile of the Ru-loaded nanoparticles is investigated on human and non-human cancer cell lines, showing IC(50) values in the low μM range against MCF-7 and WiDr cells, that is, proving to be 10-20-fold more active than AziRu, a previously synthesized NAMI-A analog, used for control. Fluorescence microscopy studies demonstrate that the amphiphilic Ru-complex/DOTAP formulations, added with rhodamine-B, are efficiently and rapidly incorporated in human MCF-7 breast adenocarcinoma cells. The intracellular fate of the amphiphilic Ru-complexes was investigated in the same in vitro model by means of an ad hoc designed fluorescently tagged analog, which exhibited a marked tendency to accumulate within or in proximity of the nuclei.
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Mangiapia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vitiello
authors.forename: Carlo
authors.initials: C
authors.lastname: Irace
authors.forename: Rita
authors.initials: R
authors.lastname: Santamaria
authors.forename: Alfredo
authors.initials: A
authors.lastname: Colonna
authors.forename: Ruggero
authors.initials: R
authors.lastname: Angelico
authors.forename: Aurel
authors.initials: A
authors.lastname: Radulescu
authors.forename: Gerardino
authors.initials: G
authors.lastname: D'Errico
authors.forename: Daniela
authors.initials: D
authors.lastname: Montesarchio
authors.forename: Luigi
authors.initials: L
authors.lastname: Paduano
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003102:Colloids; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy; D006207:Half-Life; D006801:Humans; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry; D033363:Neutron Diffraction; D010316:Particle Size; D012428:Ruthenium / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D053838:Scattering, Small Angle; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; D003102:Colloids; D056831:Coordination Complexes; D008055:Lipids; D008081:Liposomes; D013501:Surface-Active Agents; D012428:Ruthenium