Supramolecular red-light-photosensitized nitric oxide release with fluorescence self-reporting within biocompatible nanocarriers

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 12; no. 26; pp. 65 - 658
• Main Authors: Laneri, Francesca, Parisi, Cristina, Seggio, Mimimorena, Fraix, Aurore, Longobardi, Giuseppe, Catanzano, Ovidio, Quaglia, Fabiana, Sortino, Salvatore
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 03.07.2024
• Subjects: Aerobic conditions; Atomic energy levels; Biocompatibility; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biological effects; Chemical modification; Cyclodextrin; Cyclodextrins; Drug Carriers - chemistry; Effectiveness; Electromagnetic absorption; Fluorescence; Free radicals; Humans; Irradiation; Light; Micelles; Nanoparticles - chemistry; Nitric oxide; Nitric Oxide - chemistry; Nitric Oxide - metabolism; Oxygen; Particle Size; Photosensitization; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Polymers; Triplet state
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d4tb00325j

The strict dependence of the biological effects of nitric oxide (NO) on its concentration and generation site requires this inorganic free radical to be delivered with precise spatiotemporal control. Light-activation by suitable NO photoprecursors represents an ideal approach. Developing strategies to activate NO release using long-wavelength excitation light in the therapeutic window (650-1300 nm) is challenging. In this contribution, we demonstrate that NO release by a blue-light activatable NO photodonor (NOPD) with self-fluorescence reporting can be triggered catalytically by the much more biocompatible red light exploiting a supramolecular photosensitization process. Different red-light absorbing photosensitizers (PSs) are co-entrapped with the NOPD within different biocompatible nanocarriers such as Pluronic® micelles, microemulsions and branched cyclodextrin polymers. The intra-carrier photosensitized NO release, involving the lowest, long-lived triplet state of the PS as the key intermediate and its quenching by the NOPD, is competitive with that by molecular oxygen. This allows NO to be released with good efficacy, even under aerobic conditions. Therefore, the adopted general strategy provides a valuable tool for generating NO from an already available NOPD, otherwise activatable with the poorly biocompatible blue light, without requiring any chemical modification and using sophisticated and expensive irradiation sources. Red-light-triggered NO release can be triggered using different photosensitizers in different types of biocompatible nanocarriers and real-time monitored by the formation of a highly fluorescent reporter.