title: Nanoparticles loaded with ferrocenyl tamoxifen derivatives for breast cancer treatment.
abstract: For the first time, two organometallic triphenylethylene compounds (Fc-diOH and DFO), with strong antiproliferative activity in breast cancer cells, but insoluble in biological fluids, were incorporated in two types of stealth nanoparticles (NP): PEG/PLA nanospheres (NS) and nanocapsules (NC). Their physicochemical parameters were measured (size, zeta potential, encapsulation and loading efficiency), and their biological activity was assessed. In vitro drug release after high dilution of loaded NPs was measured by estradiol binding competition in MELN cells. The influence of the encapsulated drugs on the cell cycle and apoptosis was studied by flow cytometry analyses. Notwithstanding potential drug adsorption at the NP surface, Fc-diOH and DFO were incorporated efficiently in NC and NS, which slowly released both compounds. They arrested the cell cycle in the S-phase and induced apoptosis, whose activity is increased by loaded NS. A decrease in their antiproliferative activity by the antioxidant alpha-tocopherol indicated that reactive oxygen species (ROS) may be involved. Therefore, nanosystems, containing for the first time a high load of anticancer organometallic triphenylethylenes, have been developed. Their small size and delayed drug release, combined with their enhanced apoptotic potential, are compatible with an increased persistence in the blood and a promising antitumour activity.
authors.affiliation: Laboratoire de chimie et biochimie des complexes moléculaires, UMR CNRS 7576, école nationale supérieure de chimie de Paris, 11, rue Pierre-et-Marie-Curie, 75231 Paris cedex 05, France.
authors.forename: Anh
authors.initials: A
authors.lastname: Nguyen
authors.forename: Véronique
authors.initials: V
authors.lastname: Marsaud
authors.forename: Céline
authors.initials: C
authors.lastname: Bouclier
authors.forename: Siden
authors.initials: S
authors.lastname: Top
authors.forename: Anne
authors.initials: A
authors.lastname: Vessieres
authors.forename: Pascal
authors.initials: P
authors.lastname: Pigeon
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
authors.forename: Philippe
authors.initials: P
authors.lastname: Legrand
authors.forename: Gérard
authors.initials: G
authors.lastname: Jaouen
authors.forename: Jack-Michel
authors.initials: JM
authors.lastname: Renoir
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005296:Ferrous Compounds / Q000737:chemistry*; D006801:Humans; D000075163:Metallocenes; D015394:Molecular Structure; D053769:Nanocapsules / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D054118:Nanospheres / Q000737:chemistry; D010316:Particle Size; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D055672:Static Electricity; D013499:Surface Properties; D013629:Tamoxifen / Q000737:chemistry / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004965:Estrogen Antagonists; D005296:Ferrous Compounds; D000075163:Metallocenes; D053769:Nanocapsules; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D024502:alpha-Tocopherol; C004998:ferrocene