title: Imaging tumor microscopic viscosity in vivo using molecular rotors.
abstract: The microscopic viscosity plays an essential role in cellular biophysics by controlling the rates of diffusion and bimolecular reactions within the cell interior. While several approaches have emerged that have allowed the measurement of viscosity and diffusion on a single cell level in vitro, the in vivo viscosity monitoring has not yet been realized. Here we report the use of fluorescent molecular rotors in combination with Fluorescence Lifetime Imaging Microscopy (FLIM) to image microscopic viscosity in vivo, both on a single cell level and in connecting tissues of subcutaneous tumors in mice. We find that viscosities recorded from single tumor cells in vivo correlate well with the in vitro values from the same cancer cell line. Importantly, our new method allows both imaging and dynamic monitoring of viscosity changes in real time in live animals and thus it is particularly suitable for diagnostics and monitoring of the progress of treatments that might be accompanied by changes in microscopic viscosity.
authors.affiliation: Institute of Biomedical Technologies, Nizhny Novgorod State Medical Academy, Minin and Pozharsky Square, 10/1, Nizhny Novgorod, 603005, Russia.|Institute of Biology and Biomedicine, Nizhny Novgorod State University, Gagarin Avenue, 23, Nizhny Novgorod, 603950, Russia.
authors.forename: Lyubov' E
authors.initials: LE
authors.lastname: Shimolina
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, UK.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Izquierdo
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, UK.
authors.forename: Ismael
authors.initials: I
authors.lastname: López-Duarte
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Bull
authors.affiliation: Institute of Biomedical Technologies, Nizhny Novgorod State Medical Academy, Minin and Pozharsky Square, 10/1, Nizhny Novgorod, 603005, Russia.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Shirmanova
authors.affiliation: Razuvaev Institute of Organometallic Chemistry RAS, Tropinina Street, 49, Nizhny Novgorod, 603950, Russia.
authors.forename: Larisa G
authors.initials: LG
authors.lastname: Klapshina
authors.affiliation: Institute of Biomedical Technologies, Nizhny Novgorod State Medical Academy, Minin and Pozharsky Square, 10/1, Nizhny Novgorod, 603005, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Zagaynova
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, UK.
authors.forename: Marina K
authors.initials: MK
authors.lastname: Kuimova
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D009369:Neoplasms / Q000473:pathology*; D014783:Viscosity; D051598:Whole Body Imaging
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes