The development of new nanoparticles as next-generation diagnostic and therapeutic ("theranostic") drug platforms is an active area of both chemistry and cancer research. Although numerous gadolinium (Gd) containing metallofullerenes as diagnostic magnetic resonance imaging (MRI) contrast agents have been reported, the metallofullerene cage surface, in most cases, consists of negatively charged carboxyl or hydroxyl groups that limit attractive forces with the cellular surface. It has been reported that nanoparticles with a positive charge will bind more efficiently to negatively charged phospholipid bilayer cellular surfaces, and will more readily undergo endocytosis. In this paper, we report the preparation of a new functionalized trimetallic nitride template endohedral metallofullerene (TNT EMF), Gd3N@C80(OH)x(NH2)y, with a cage surface bearing positively charged amino groups (-NH3(+)) and directly compare it with a similar carboxyl and hydroxyl functionalized derivative. This new nanoparticle was characterized by X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and infrared spectroscopy. It exhibits excellent (1)H MR 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-13Rα2. We also report that this amino-coated Gd-nanoplatform, when subsequently conjugated with interleukin-13 peptide IL-13-Gd3N@C80(OH)x(NH2)y, exhibits enhanced targeting of U-251 GBM cell lines and can be effectively delivered intravenously in an orthotopic GBM mouse model.
Glioblastoma multiforme (GBM) brain tumors represent a devastating disease with no really effective treatment. GBM carries a life expectancy from the time of diagnosis of about 14 months.In this paper we report results for a novel carbonaceous platform, namely, endohedral metallofullerenes (Gd-EMF-IL-13 and 177Lu-EMF-IL-13), as a new multi-modal “theranostic” platform for the diagnosis and treatment of infiltrative GBM tumors. The targeting modality is a cytokine, interleukin-13 (IL-13), which is over-expressed in human and animal GBM cell lines, and is a key addition to the nanoparticle platform that has not been previously employed in therapeutic EMF studies. Our recent results for preparing and in vivo results for multi-modal endohedral metallofullerenes will be the focus of this presentation.1
References:
1. Zhang, J.; Stevenson, S.; Dorn, H.C. Trimetallic Nitride Endohedral Metallofullerenes: Discovery, Structural Characterization, Reactivity, and Applications. Accounts of Chemical Research, 2013, 46(7), 1548-1557
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