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Amino-Coated Metallofullerene Nanoparticles for Glioblastoma Mutiforme Tumor Detection

Water-soluble derivatives of gadolinium-containing metallofullerenes have been synthesized and tested as excellent candidates for magnetic resonance imaging (MRI) contrast agents because of their high relaxivity and robustness. It is expected that nanoparticles with a positive charge will bind more efficiently to negatively charged cell phospholipid bi-layer cellular surfaces and will more readily undergo endocytosis. Although numerous gadolinium-containing metallofullerenes diagnostic MRI contrast agents have been reported, the metallofullerene cage surface in most cases consist of negatively charged carboxyl or hydroxyl groups that limits attractive forces with the cellular surface. In this paper, we report the preparation of a new functionalized trimetallic nitride endohedral metallofullerene, Gd3N@C80(OH)x(NH2)y with a cage surface consisting of positively charged amino groups. This new nanoparticle was characterized by X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), reflection-absorption IR spectroscopy (RAIRS), NMR, and exhibit excellent 1H relaxivity. Previous studies have clearly demonstrated that the cytokine, interleukin-13 (IL-13) effectively targets glioblastoma multiforme (GBM) cells which are known to overexpress IL-13 receptors (IL-13Rα) sites. We now report that this Gd-nanoplatform when subsequently conjugated with an IL-13 peptide, (IL-13-Gd3N@C80(OH)x(NH2)y)exhibits enhanced targeting of U-251 GBM cell lines. These results support the hypothesis that positively charged nanoparticles provide enhanced cell surface charge attraction for GBM cellular endocytosis.
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