2-Deoxy-D-Glucose Modified Magnetic Nanoparticles with Dual Functional Properties: Nanothermotherapy and Magnetic Resonance Imaging.

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) with appropriate surface chemistry have attracted wild attention in medical and biological application because of their current and potential usefulness such as magnetic resonance imaging (MRI) contrast enhancement, magnetic mediated hyperthermia (MMH), immunoassay, and in drug delivery, etc. In this study, we investigated the MRI contrast agents and MMH mediators properties of the novel 2-deoxy-D-glucose (2-DG) modified SPIONs. As a non-metabolizable glucose analogue, 2-DG can block glycolysis and inhibits protein glycosylation. Moreover, SPIONs coated with 2-DG molecules can be particularly attractive to resource-hungry cancer cells, therefore to realize the targeting strategy for the SPIONs. SPIONs with amino silane as the capping agent for amino-group surface modification were synthesized by the chemical co-precipitation method with modification. Glutaraldehyde was further applied as an activation agent through which 2-DG was conjugated to the amino-coated SPIONs. Physicochemical characterizations of the 2-DG-SPIONs, such as surface morphology, surface charge and magnetic properties were investigated by Transmission Electron Microscopy (TEM), ζ-Potential and Vibrating Sample Magnetometer (VSM), etc. Magnetic inductive heating characteristics of the 2-DG-SPIONs were analyzed by exposing the SPIONs suspension (magnetic fluid) under alternative magnetic field (AMF). U-251 human glioma cells with expression of glucose transport proteins type 1 and 3 (GLUT1 and GLUT 3), and L929 murine fibroblast cell as negative control, were employed to study the effect of 2-DG modification on the cell uptake for SPIONs. TEM images for ultra-thin sections as well as ICP-MS were applied to evaluate the SPIONs internalization within the cells. In vitro MRI was performed after cells were co-incubated with SPIONs and the T2 relaxation time was measured and compared. The results demonstrate that 2-DG-SPIONs were supermagnetic and in spherical shape with -10 nm diameter. Possessing ideal magnetic inductive heating characteristics, which can generate very rapid and efficient heating while upon AMF exposure, 2-DG-SPIONs can be applied as novel candidature of magnetic nanothermotherapy for cancer treatment. Modification of 2-DG can greatly promote the cell uptake of SPIONs and such cellular uptake of 2-DG-SPIONs was time dependent. Surface coating by 2-DG can remarkably enhance the MR imaging ability for the SPIONs on the cells of U251 cancer cells. In summary, our investigation provides a novel glucose analogue modified SPIONs with potential application in the targeting cancer nanothermotherapy and MR imaging.