| 研究概要 |
Functional cellular substrates for localized cell stimulation by small molecules provide an opportunity to control and monitor cell-signaling 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.
We have targeted nitric oxide (NO), a crucial signaling molecule with site-specific and concentration-dependent activities and proposed a new synthetic strategy for developing spatiotemporally controllable NO-releasing platforms based on photoactive porous coordination polymers (PCPs). By reacting nitroimidazole-based ligands in the presence of zinc salts, we have obtained and characterized new three-dimensional crystalline porous coordination structures. We have shown efficient and controllable light-induced NO release under light irradiation using a NO-selective detection technique.
In order to demonstrate the applicability of these materials for the delivery of NO in biological environments, we have embedded the photoactive PCP crystals into a biocompatible polymer matrix suitable for cell culture. By combining confocal microscope imaging and near-infrared two-photon laser activation we have shown for the first time precisely controlled NO delivery at the cellular level. Finally, the biological relevance of the exogenous NO produced by the PCPs was evidenced by intracellular change in calcium concentration, mediated by an NO-responsive plasma-membrane channel protein.
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