RESUMO
Multiple formulations of iron oxide nanoparticles (IONPs) have been proposed for enhancing contrast in magnetic resonance imaging (MRI) and for increasing efficacy in thermal ablation therapies. However, insufficient accumulation at the disease site and low magnetic performance hamper the clinical application of IONPs. Here, 20 nm iron oxide nanocubes were assembled into larger nanoconstructs externally stabilized by a serum albumin coating. The resulting assemblies of nanocubes (ANCs) had an average diameter of 100 nm and exhibited transverse relaxivity (r2 = 678.9 ± 29.0 mMâ1·sâ1 at 1.41 T) and heating efficiency (specific absorption rate of 109.8 ± 12.8 W·gâ1 at 512 kHz and 10 kA·mâ1). In mice bearing glioblastoma multiforme tumors, Cy5.5-labeled ANCs allowed visualization of malignant masses via both near infrared fluorescent and magnetic resonance imaging. Also, upon systemic administration of ANCs (5 mgFe·kgâ1), 30 min of daily exposure to alternating magnetic fields for three consecutive days was sufficient to halt tumor progression. This study demonstrates that intravascular administration of ANCs can effectively visualize and treat neoplastic masses.
RESUMO
PURPOSE: Sonodynamic therapy is a developing noninvasive modality for cancer treatment, based on the selective activation of a sonosensitizer agent by acoustic cavitation. The activated sonosensitizer agent might generate reactive oxygen species leading to cancer cell death. We investigated the potential poly-methyl methacrylate core-shell nanoparticles (NPs) loaded with meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) have to function as an innovative sonosensitizing system, ie, TPPS-NPs. METHODS: Shockwaves (SWs) generated by a piezoelectric device were used to induce acoustic cavitation. The cytotoxic effect of the sonodynamic treatment with TPPS-NPs and SWs was investigated on the human neuroblastoma cell line, SH-SY5Y. Cells were exposed for 12 hours to TPPS-NPs (100 µg/mL) and then to SWs (0.43 mJ/mm(2) for 500 impulses, 4 impulses/second). Treatment with SWs, TPPS, and NPs alone or in combination was carried out as control. RESULTS: There was a statistically significant decrease in SH-SY5Y cell proliferation after the sonodynamic treatment with TPPS-NPs and SWs. Indeed, there was a significant increase in necrotic (16.91% ± 3.89%) and apoptotic (27.45% ± 3.03%) cells at 48 hours. Moreover, a 15-fold increase in reactive oxygen species production for cells exposed to TPPS-NPs and SWs was observed at 1 hour compared with untreated cells. A statistically significant enhanced mRNA (messenger ribonucleic acid) expression of NRF2 (P<0.001) and a significant downregulation of TIGAR (P<0.05) and MAP3K5 (P<0.05) genes was observed in cells exposed to TPPS-NPs and SWs at 24 hours, along with a statistically significant release of cytochrome c (P<0.01) at 48 hours. Lastly, the sonosensitizing system was also investigated in an in vitro three-dimensional model, and the sonodynamic treatment significantly decreased the neuroblastoma spheroid growth. CONCLUSION: The sonosensitizing properties of TPPS were significantly enhanced once loaded onto NPs, thus enhancing the sonodynamic treatment's efficacy in an in vitro neuroblastoma model.
Assuntos
Ondas de Choque de Alta Energia/uso terapêutico , Nanopartículas/química , Neuroblastoma/metabolismo , Porfirinas/farmacologia , Radiossensibilizantes/farmacologia , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos da radiação , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Fotoquimioterapia , Polímeros , Porfirinas/química , Radiossensibilizantes/química , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/efeitos da radiaçãoRESUMO
This study is focused on the realization of nanodevices for nano and molecular electronics, based on molecular interactions in a metal-molecule-metal (M-M-M) structure. In an M-M-M system, the electronic function is a property of the structure and can be characterized through I/V measurements. The contact between the metals and the molecule was obtained by gold nanogaps (with a dimension of less than 10 nm), produced with the electromigration technique. The nanogap fabrication was controlled by a custom hardware and the related software system. The studies were carried out through experiments and simulations of organic molecules, in particular oligothiophenes.
RESUMO
This paper presents an innovative, portable and low power blood cell counter, based on micro-electro-mechanical-systems (MEMS) technology. It was realized by designing and developing a custom impedance measurement circuit, which drives an electro-fluidic microsystem, providing a parallel, multi-channel Coulter counter. A method for a reliable, easy, and low-cost interfacing to such kind of micro-devices, allowing both fluidic and electric coupling, is also shown. Preliminary experiments led to promising results: fluidics works properly without leakages or clogging. Electrodes show good stability with current (in terms of adhesion), and measured channel impedances are satisfyingly low (30 kW for a cubic Coulter orifice, side 10 microm). Finally, we present a possible extension of the setup, based on a dual-characteristic, electro-optical counting.