Abstract
Iron oxide nanoparticles (IONP) can have a variety of biomedical applications due to their visualization properties through Magnetic Resonance Imaging (MRI) and heating with radio frequency or alternating magnetic fields. In the oncological field, coating IONP with organic compounds to provide specific features and to achieve the ability of binding specific molecular targets appears to be very promising. To take advantage of the high avidity of tumor cells for glucose, we report the development of very small glucose-coated IONP (glc-IONP) by employing an innovative technique, Metal Vapor Synthesis (MVS). Moreover, we tested the internalization of our gl-IONP on a tumor line, BxPC3, over-expressing GLUT 1 transporter. Both glc-IONP and polyvinylpyrrolidone-IONP (PVP-IONP), as control, were prepared with MVS and were tested on BxPC3 at various concentrations. To evaluate the role of GLUT-1 transporter, we also investigated the effect of adding a polyclonal anti-GLUT1 antibody. After proper treatment, the iron value was assessed by atomic absorption spectrometer, reported in mcg/L and expressed in mg of protein. Our IONP prepared with MVS were very small and homogeneously distributed in a narrow range (1.75-3.75 nm) with an average size of 2.7 nm and were super-paramagnetic. Glc-IONP were internalized by BxPC3 cells in a larger amount than PVP-IONP. After 6h of treatment with 50 mcg/mL of IONPs, the content of Fe was 1.5 times higher in glc-IONP-treated cells compared with PVP-IONP-treated cells. After 1h pre-treatment with anti-GLUT1, a reduction of 41% cellular accumulation of glc-IONP was observed. Conversely, the uptake of PVP-IONPs was reduced only by 14% with antibody pretreatment. In conclusion, MVS allowed us to prepare small, homogeneous, super-paramagnetic glc-IONP, which are electively internalized by a tumor line over-expressing GLUT1. Our glc-IONP appear to have many requisites for in vivo use.
Highlights
Iron oxide nanoparticles (IONP) can have a variety of biomedical applications such as drug delivery, Magnetic Resonance Imaging (MRI) and endogenous hyperthermia by heating IONP with radio frequency or alternating magnetic fields [1,2,3,4,5,6,7]
To take advantage of the high avidity of tumor cells for glucose, we report the development of very small glucose-coated IONP by employing an innovative technique, Metal Vapor Synthesis (MVS)
One of the most widely documented metabolic activities in tumors is the so-called Warburg effect named after Otto Warburg who, in the 1920s, observed that tumor cells consume a large amount of glucose, much more than normal cells, and convert most of it to lactic acid [23]
Summary
Iron oxide nanoparticles (IONP) can have a variety of biomedical applications such as drug delivery, Magnetic Resonance Imaging (MRI) and endogenous hyperthermia by heating IONP with radio frequency or alternating magnetic fields [1,2,3,4,5,6,7]. Coating IONP with organic compounds to provide specific features and to achieve the ability of binding specific molecular targets represents one of the most promising fields of study [1,2,3]. As is known, increased glucose uptake, mainly through glycolitic anaerobic pathway, is one of the earliest and well-recognized metabolic alterations in the transformed cell [23]. This anomaly, known as the Warburg effect, represents the rationale of Positron Emission Tomography (PET) using Fluorine-18-fluorodeoxyglucose (18-FDG), which, either alone or combined with computed tomography, has become a routine clinical test for the diagnosis and staging of cancer [17]. GLUT1 could represent a useful way for transporting nanomolecules inside cancer cells
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