Regulation of Nitric Oxide (NO) Release by Membrane Fluidity in Ruthenium Nitrosyl Complex-Embedded Phospholipid Vesicles

Incorporating water-insoluble nitric oxide (NO)-releasing molecules into biocompatible vesicles may allow for the tunable control of NO release on a specific target site. In vesicles, membrane fluidity plays an important role and influences the final therapeutic efficiency of drugs loaded into the vesicles. Hence, we aimed to investigate the effect of lipid fluidity on the NO release behavior of the photo-controllable ruthenium nitrosyl (Ru-NO) complex. In this regard, a new photoactive ruthenium nitrosyl complex (L.Ru-NO) with amphiphilic terpyridine ligand was synthesized and characterized in detail. L.Ru-NO was incorporated with commercial phospholipids to form nanoscale vesicles L.Ru-NO@Lip. The photoactive {Ru-NO}6 type complex released NO in the organic solvent CH3CN and aqueous liposome solution by irradiating under low-intensity blue light (λ = 410 nm, 3 W). To demonstrate the effect of lipid structure and fluidity on NO release, four different liposome systems L.Ru-NO@Lip1-4 were prepared by using phospholipids such as DOPC, DSPC, DPPC, and DMPC having different chain lengths and saturation. The NO-releasing abilities of these liposomes in aqueous medium were studied by UV-vis spectrum, colorimetric Greiss, and fluorescent DAF assay. The results show that the rate of NO release could be easily tuned by varying the lipid fluidity. The effect of temperature and pH on NO release was also studied. Further, the complex L.Ru-NO and liposomes L.Ru-NO@Lip1 were assayed as an antibacterial agent against the strains of bacteria Escherichia coli and Staphylococcus aureus.