title: Localized cell stimulation by nitric oxide using a photoactive porous coordination polymer platform.
abstract: Functional cellular substrates for localized cell stimulation by small molecules provide an opportunity to control and monitor cell signalling networks chemically in time and space. However, despite improvements in the controlled delivery of bioactive compounds, the precise localization of gaseous biomolecules at the single-cell level remains challenging. Here we target nitric oxide, a crucial signalling molecule with site-specific and concentration-dependent activities, and we report a synthetic strategy for developing spatiotemporally controllable nitric oxide-releasing platforms based on photoactive porous coordination polymers. By organizing molecules with poor reactivity into polymer structures, we observe increased photoreactivity and adjustable release using light irradiation. We embed photoactive polymer crystals in a biocompatible matrix and achieve precisely controlled nitric oxide delivery at the cellular level via localized two-photon laser activation. The biological relevance of the exogenous nitric oxide produced by this strategy is evidenced by an intracellular change in calcium concentration, mediated by nitric oxide-responsive plasma membrane channel proteins.
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Diring
authors.forename: Dan Ohtan
authors.initials: DO
authors.lastname: Wang
authors.forename: Chiwon
authors.initials: C
authors.lastname: Kim
authors.forename: Mio
authors.initials: M
authors.lastname: Kondo
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Susumu
authors.initials: S
authors.lastname: Kitagawa
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Kamei
authors.forename: Shuhei
authors.initials: S
authors.lastname: Furukawa
mesh_terms: D000814:Aniline Compounds; D001672:Biocompatible Materials; D002118:Calcium / Q000378:metabolism*; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005456:Fluorescent Dyes; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D008856:Microscopy, Fluorescence; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000737:chemistry*; D055668:Photochemical Processes; D016062:Porosity; D059010:Single-Cell Analysis; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D001672:Biocompatible Materials; D004129:Dimethylpolysiloxanes; C409648:Fluo 4; D005456:Fluorescent Dyes; D009593:Nitroimidazoles; D014966:Xanthenes; D009569:Nitric Oxide; C013830:baysilon; D002118:Calcium