Glutathione Responsive β-Cyclodextrin Conjugated S-Nitrothiols as a Carrier for Intracellular Delivery of Nitric Oxide

Nitric oxide (NO) exerts multiple functions in many life processes and was of great significance in a variety of biomedical scenarios. However, the mismatches between releasing locations and NO active sites seriously limited the available NO at areas of interest and greatly dampen the overall efficiency of delivery systems. Therefore, in the present study, a NO donor was developed to achieve intracellular delivery and release of NO to overcome the aforementioned challenges. Enhanced uptake and effective intracellular release of NO were realized via β-cyclodextrin (β-CD) mediated endocytosis and high level glutathione (GSH) inside cells, respectively. We demonstrated that intracellularly delivered NO would exert stronger bioeffects than premature release of NO outside targeted cells. Besides, β-CD assisted cellular uptake proved indispensable in maximizing the influence of NO in modulating cellular behavior. These results demonstrated the significance of intracellular delivery and release of NO in improvin...