Localized cell stimulation by nitric oxide using a photoactive porous coordination polymer platform

• Published in: Nature communications Vol. 4; no. 1; p. 2684
• Main Authors: Diring, Stéphane, Wang, Dan Ohtan, Kim, Chiwon, Kondo, Mio, Chen, Yong, Kitagawa, Susumu, Kamei, Ken-ichiro, Furukawa, Shuhei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.10.2013; Nature Publishing Group; Nature Pub. Group
• Subjects: 121/135; 14/19; 639/638/263; 639/638/298/923/1028; Aniline Compounds; Biocompatible Materials; Calcium - metabolism; Crystals; Dimethylpolysiloxanes - chemistry; Drug Delivery Systems - methods; Fluorescent Dyes; HEK293 Cells; Humanities and Social Sciences; Humans; Ligands; Light; Localization; Microscopy, Fluorescence; multidisciplinary; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide - pharmacology; Nitroimidazoles - chemistry; Photochemical Processes; Physiology; Polymers; Porosity; Science; Science (multidisciplinary); Single-Cell Analysis; Xanthenes; Japan
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms3684

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. Localized cell stimulation is useful in the analysis of biological signalling networks. Here the authors develop a photosensitive porous framework to achieve spatiotemporally controlled cellular delivery of the gaseous biomolecule nitric oxide, using it to regulate intracellular calcium levels.