A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells

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• 作者：Tinghui Li ; Susan Murphy ; Boris Kiselev ; Kanwarpal S. Bakshi ; Jianyuan Zhang ; Amnah Eltahir ; Yafen Zhang ; Ying Chen ; Jie Zhu ; Richey M. Davis ; Louis A. Madsen ; John R. Morris ; Daniel R. Karolyi ; Stephen M. LaConte ; Zhi Sheng ; Harry C. Dorn
• 刊名：Journal of the American Chemical Society
• 出版年：2015
• 出版时间：June 24, 2015
• 年：2015
• 卷：137
• 期：24
• 页码：7881-7888
• 全文大小：460K
• ISSN：1520-5126

文摘

The development of new nanoparticles as next-generation diagnostic and therapeutic (鈥渢heranostic鈥? 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 (鈭扤H₃⁺) 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 ¹H 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-13R伪2. 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.