title: Zero-valent Fe confined mesoporous silica nanocarriers (Fe(0) @ MCM-41) for targeting experimental orthotopic glioma in rats.
abstract: Mesoporous silica nanoparticles (MSNs) impregnated with zero-valent Fe (Fe(0) @ MCM-41) represent an attractive nanocarrier system for drug delivery into tumor cells. The major goal of this work was to assess whether MSNs can penetrate the blood-brain barrier in a glioblastoma rat model. Synthesized MSNs nanomaterials were characterized by energy dispersive X-ray spectroscopy, measurements of X-ray diffraction, scanning electron microscopy and Mössbauer spectroscopy. For the detection of the MSNs by MR and for biodistribution studies MSNs were labeled with zero-valent Fe. Subsequent magnetometry and nonlinear-longitudinal-response-M2 (NLR-M2) measurements confirmed the MR negative contrast enhancement properties of the nanoparticles. After incubation of different tumor (C6 glioma, U87 glioma, K562 erythroleukemia, HeLa cervix carcinoma) and normal cells such as fibroblasts and peripheral blood mononuclear cells (PBMCs) MSNs rapidly get internalized into the cytosol. Intracellular residing MSNs result in an enhanced cytotoxicity as Fe(0) @ MCM-41 promote the reactive oxygen species production. MRI and histological studies indicated an accumulation of intravenously injected Fe(0) @ MCM-41 MSNs in orthotopic C6 glioma model. Biodistribution studies with measurements of second harmonic of magnetization demonstrated an increased and dose-dependent retention of MSNs in tumor tissues. Taken together, this study demonstrates that MSNs can enter the blood-brain barrier and accumulate in tumorous tissues.
authors.affiliation: Klinikum rechts der Isar, Department Radiation Oncology, Technische Universität München, Ismaniger Str. 22, Munich 81675, Germany.|Institute of Cytology of the Russian Academy of Sciences (RAS), St. Petersburg, 194064 Tikhoretsky ave., 4, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Shevtsov
authors.affiliation: Saint Petersburg State University, St. Petersburg, Universitetskaya nab. 7 - 9, 199034, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Parr
authors.affiliation: NRC "Kurchatov Institute", B.P. Konstantinov Petersburg Nuclear Physics Institute, Gatchina 188300, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Ryzhov
authors.affiliation: Saint Petersburg State University, St. Petersburg, Universitetskaya nab. 7 - 9, 199034, Russia.
authors.forename: E G
authors.initials: EG
authors.lastname: Zemtsova
authors.affiliation: Saint Petersburg State University, St. Petersburg, Universitetskaya nab. 7 - 9, 199034, Russia.
authors.forename: A Yu
authors.initials: AY
authors.lastname: Arbenin
authors.affiliation: Saint Petersburg State University, St. Petersburg, Universitetskaya nab. 7 - 9, 199034, Russia.
authors.forename: A N
authors.initials: AN
authors.lastname: Ponomareva
authors.affiliation: Saint Petersburg State University, St. Petersburg, Universitetskaya nab. 7 - 9, 199034, Russia.
authors.forename: V M
authors.initials: VM
authors.lastname: Smirnov
authors.affiliation: Klinikum rechts der Isar, Department Radiation Oncology, Technische Universität München, Ismaniger Str. 22, Munich 81675, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Multhoff
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D004705:Endocytosis; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007501:Iron / Q000032:analysis*; D008279:Magnetic Resonance Imaging; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D012822:Silicon Dioxide / Q000032:analysis*; D013052:Spectrometry, X-Ray Emission; D015204:Spectroscopy, Mossbauer; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; C509968:MCM-41; D012822:Silicon Dioxide; D007501:Iron