Nitric Oxide-Photodelivering Materials with Multiple Functionalities: From Rational Design to Therapeutic Applications.

The achievement of materials that are able to release therapeutic agents under the control of light stimuli to improve therapeutic efficacy is a significant challenge in health care. Nitric oxide (NO) is one of the most studied molecules in the fascinating realm of biomedical sciences, not only for its crucial role as a gaseous signaling molecule in the human body but also for its great potential as an unconventional therapeutic in a variety of diseases including cancer, bacterial and viral infections, and neurodegeneration. Handling difficulties due to its gaseous nature, reduced region of action due to its short half-life, and strict dependence of the biological effects on its concentration and generation site are critical questions to be solved for appropriate therapeutic uses of NO.

Simultaneous photoactivation of a fluoroquinolone antibiotic and nitric oxide with fluorescence reporting.

The achievement of smart pharmaceuticals whose bioactivity can be spatiotemporally controlled by light stimuli is known as photopharmacology, an emerging area aimed at improving the therapeutic outcome and minimizing side effects. This is especially attractive for antibiotics, for which the inevitable development of multidrug resistance and the dwindling of new clinically approved drugs represent the main drawbacks. Here, we show that nitrosation of the fluoroquinolone norfloxacin (NF), a broad-spectrum antibiotic, leads to the nitrosated bioconjugate NF-NO, which is inactive at the typical minimum inhibitory concentration of NF.

Stepwise Nitric Oxide Release and Antibacterial Activity of a Nitric Oxide Photodonor Hosted within Cyclodextrin Branched Polymer Nanocarriers.

A hydrophobic nitric oxide (NO) photodonor integrating both nitroso and nitro functionalities within its chromophoric skeleton has been synthesized. Excitation of this compound with blue light triggers the release of two NO molecules from the nitroso and the nitro functionalities via a stepwise mechanism. Encapsulation of the NO photodonor within biocompatible neutral, cationic, and anionic β-cyclodextrin branched polymers as suitable carriers leads to supramolecular nanoassemblies, which exhibit the same nature of the photochemical processes but NO photorelease performances enhanced by about 1 order of magnitude when compared with the free guest.

Supramolecular Assemblies of Fluorescent Nitric Oxide Photoreleasers with Ultrasmall Cyclodextrin Nanogels.

Developing biocompatible nitric oxide (NO) photoreleasing nanoconstucts is of great interest in view of the large variety of biological roles that NO plays and the unique advantage light offers in controlling NO release in space and time. In this contribution, we report the supramolecular assemblies of two NO photodonors (NOPDs), NBF-NO and RHD-NO, as water-dispersible nanogels, ca. 10 nm in diameter, based on γ-cyclodextrins (γ-CDng).

The Influence of Some Axial Ligands on Ruthenium-Phthalocyanine Complexes: Chemical, Photochemical, and Photobiological Properties.

This work presents a new procedure to synthesize ruthenium-phthalocyanine complexes and uses diverse spectroscopic techniques to characterize [RuCl(Pc)DMSO] (Pc = phthalocyanine) and -[Ru(Pc)(4-ampy)] (4-ampy = 4-aminopyridine). The triplet excited-state lifetimes of measured by nanosecond transient absorption showed that two processes occurred, one around 15 ns and the other around 3.8 μs.

Photobiomodulation combined with photodynamic therapy using ruthenium phthalocyanine complexes in A375 melanoma cells: Effects of nitric oxide generation and ATP production.

Light irradiation has been used in clinical therapy for several decades. In this context, photobiomodulation (PBM) modulates signaling pathways via ROS, ATP, Ca, while photodynamic therapy (PDT) generates reactive oxygen species by excitation of a photosensitizer. NO generation could be an important tool when combined with both kinds of light therapy.