title: A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells.
abstract: 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.
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.
authors.forename: Tinghui
authors.initials: T
authors.lastname: Li
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Murphy
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.|∥Virginia Tech Carilion School of Medicine, Roanoke, Virginia 24016, United States.
authors.forename: Boris
authors.initials: B
authors.lastname: Kiselev
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.|∥Virginia Tech Carilion School of Medicine, Roanoke, Virginia 24016, United States.
authors.forename: Kanwarpal S
authors.initials: KS
authors.lastname: Bakshi
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.
authors.forename: Jianyuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.
authors.forename: Amnah
authors.initials: A
authors.lastname: Eltahir
authors.forename: Yafen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Richey M
authors.initials: RM
authors.lastname: Davis
authors.forename: Louis A
authors.initials: LA
authors.lastname: Madsen
authors.forename: John R
authors.initials: JR
authors.lastname: Morris
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.|∥Virginia Tech Carilion School of Medicine, Roanoke, Virginia 24016, United States.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Karolyi
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: LaConte
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: †Virginia Tech Carilion Research Institute, Roanoke, Virginia 24016, United States.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Dorn
mesh_terms: D000586:Amination; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D037741:Fullerenes / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D005909:Glioblastoma / Q000175:diagnosis*; D006801:Humans; D018793:Interleukin-13 / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008819:Mice, Nude; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D037741:Fullerenes; D018793:Interleukin-13; D005682:Gadolinium