Emerging frontiers in long-wavelength light-triggered nitric oxide release for therapeutic applications

Nitric oxide (NO) is a pivotal signaling molecule whose therapeutic potential is constrained by challenges in controlled delivery. Photocontrolled strategies employing red to near-infrared (NIR) light, known for deep tissue penetration and minimal phototoxicity, present transformative opportunities for spatiotemporally precise NO release. This review surveys emerging red/NIR-activated NO release platforms and elucidates core photochemical strategies, including direct red/NIR absorption by engineered NO donors, upconversion nanoparticles (UCNPs), two-photon excitation, and photoredox catalysis. These approaches demonstrate significant promise in a variety of applications, including targeted oncological therapies, antimicrobial interventions, and anti-inflammatory treatments, among others. A critical appraisal of prevailing challenges and future directions underscores the need for enhanced efficiency, biocompatibility, and multifunctional integration to facilitate clinical translation.