title: Functionalization of graphene oxide nanostructures improves photoluminescence and facilitates their use as optical probes in preclinical imaging.
abstract: Recently reported photoluminescent nanographene oxides (nGOs), i.e. nanographene oxidised with a sulfuric/nitric acid mixture (SNOx method), have tuneable photoluminescence and are scalable, simple and fast to produce optical probes. This material belongs to the vast class of photoluminescent carbon nanostructures, including carbon dots, nanodiamonds (NDs), graphene quantum dots (GQDs), all of which demonstrate a variety of properties that are attractive for biomedical imaging such as low toxicity and stable photoluminescence. In this study, the nGOs were organically surface-modified with poly(ethylene glycol)-poly(ethylene imine) (PEG-PEI) copolymers tagged with folic acid as the affinity ligand for cancer cells expressing folate receptors. The functionalization enhanced both the cellular uptake and quantum efficiency of the photoluminescence as compared to non-modified nGOs. The nGOs exhibited an excitation dependent photoluminescence that facilitated their detection with a wide range of microscope configurations. The functionalized nGOs were non-toxic, they were retained in the stained cell population over a period of 8 days and they were distributed equally between daughter cells. We have evaluated their applicability in in vitro and in vivo (chicken embryo CAM) models to visualize and track migratory cancer cells. The good biocompatibility and easy detection of the functionalized nGOs suggest that they could address the limitations faced with quantum dots and organic fluorophores in long-term in vivo biomedical imaging.
authors.affiliation: Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland. jerosenh@abo.fi.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Prabhakar
authors.forename: Tuomas
authors.initials: T
authors.lastname: Näreoja
authors.forename: Eva
authors.initials: E
authors.lastname: von Haartman
authors.forename: Didem
authors.initials: D
authors.lastname: Şen Karaman
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Burikov
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Dolenko
authors.forename: Takahiro
authors.initials: T
authors.lastname: Deguchi
authors.forename: Veronika
authors.initials: V
authors.lastname: Mamaeva
authors.forename: Pekka E
authors.initials: PE
authors.lastname: Hänninen
authors.forename: Igor I
authors.initials: II
authors.lastname: Vlasov
authors.forename: Olga A
authors.initials: OA
authors.lastname: Shenderova
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Rosenholm
mesh_terms: D000818:Animals; D002465:Cell Movement; D058948:Cell Tracking / Q000379:methods*; D006108:Graphite / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008163:Luminescent Measurements / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods*; D015336:Molecular Probe Techniques; D015335:Molecular Probes; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000737:chemistry* / Q000473:pathology*; D010087:Oxides / Q000737:chemistry; D013347:Subcellular Fractions / Q000737:chemistry / Q000473:pathology
chemical_list: D015335:Molecular Probes; D010087:Oxides; D006108:Graphite