title: A Novel Nanoprobe for Multimodal Imaging Is Effectively Incorporated into Human Melanoma Metastatic Cell Lines.
abstract: To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T₁ relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/μL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe.
authors.affiliation: NorLux Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway. synnovenymarkaasen@gmail.com.
authors.forename: Synnøve Nymark
authors.initials: SN
authors.lastname: Aasen
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague, Czech Republic. pospisilova-a@seznam.cz.
authors.forename: Aneta
authors.initials: A
authors.lastname: Pospisilova
authors.affiliation: Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway. tilo.eichler@k1.uib.no.
authors.forename: Tilo Wolf
authors.initials: TW
authors.lastname: Eichler
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague, Czech Republic. panek@imc.cas.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Panek
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague, Czech Republic. mhruby@centrum.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Hruby
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague, Czech Republic. ppetr.stepanek@gmail.com.
authors.forename: Petr
authors.initials: P
authors.lastname: Stepanek
authors.affiliation: Molecular Imaging Center, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway. endy.spriet@uib.no.
authors.forename: Endy
authors.initials: E
authors.lastname: Spriet
authors.affiliation: Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic. daji@medicon.cz.|Institute of Biophysics and Informatics, 1st Medicine Faculty, Charles University, 120 00 Prague, Czech Republic. daji@medicon.cz.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jirak
authors.affiliation: NorLux Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway. kaioveskaftnesmo@gmail.com.
authors.forename: Kai Ove
authors.initials: KO
authors.lastname: Skaftnesmo
authors.affiliation: NorLux Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway. frits.thorsen@uib.no.|Molecular Imaging Center, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway. frits.thorsen@uib.no.|Kristian Gerhard Jebsen Brain Tumour Research Centre, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway. frits.thorsen@uib.no.
authors.forename: Frits
authors.initials: F
authors.lastname: Thorsen
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D003287:Contrast Media / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes; D064847:Multimodal Imaging; D036103:Nanotechnology; D013050:Spectrometry, Fluorescence; D013194:Staining and Labeling
chemical_list: D003287:Contrast Media; D015335:Molecular Probes; D006003:Glycogen
keywords: fluorescence lifetime correlation spectroscopy; fluorescence microscopy; high throughput microscopy; magnetic resonance imaging; melanoma brain metastasis; nanoprobe; theranostics; zeta potential