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.
Highlights
Glioblastoma multiforme (GBM) is highly aggressive primary brain tumor that is associated with high morbidity and poor prognosis
Following incorporation of the zero-valent Fe into the Mesoporous silica nanoparticles (MSNs) we could detect the ferrum in the pores though we did not observe the change in the size of the particles
Comparison of spectra of energy dispersive X-ray (EDX) from Fe(0) @ MCM-41 nanoparticles and empty MSNs demonstrated the presence of the peak originating from iron (Fig. 1E)
Summary
Glioblastoma multiforme (GBM) is highly aggressive primary brain tumor that is associated with high morbidity and poor prognosis. One of the currently available nanocarrier systems are nanoparticles based on silica. Mesoporous silica-based nanoparticles (MSNs) represent an attractive system for a controlled release of anticancer drugs including chemotherapeutic agents, small interfering RNAs (siRNA), radiotherapy sensitizers[3,4,5,6]. Up-to-date studies demonstrated the therapeutic efficacy of MSNs for targeting glioma cells in in vitro experiments. In a recent work of Huang et al retention of MSNs was revealed in an orthotopic U87MG glioblastoma model where mesenchymal stem cells were applied for the transportation of the MSNs16. In the present investigations the ability of Fe(0) @ MCM-41 nanoparticles for targeting the brain tumor was investigated in the model of orthotopic C6 glioma with application of the magnetic resonance imaging (MRI). The study of biodistribution of magnetic nanoparticles was carried out applying the sensitive measurements of second harmonic generation in parallel dc H and weak ac h(t) magnetic fields (NLR-M2)[17]
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