NIR imaging-guided carbon monoxide nanomedicine: Design strategies, stimuli-responsive release, and multimodal synergistic therapies for precision disease treatment

Endogenous gaseous molecules, especially carbon monoxide (CO), exhibit unique therapeutic potential in regulating cancer, infections, and inflammation owing to their dose-dependent bioactivity and multi-faceted mechanisms. However, challenges in spatiotemporal control and real-time monitoring of CO delivery hinder clinical translation. The integration of near-infrared II (NIR-II) imaging with CO nanodelivery systems provides a promising avenue for precise visualization and controlled gas therapy, offering deep tissue penetration, high resolution, and a favorable signal-to-noise ratio for guided therapy. This review systematically summarizes recent advances in NIR-II-guided CO nanoplatforms, focusing on design strategies, including polymers, core-shell structures, Metal-Organic Frameworks (MOFs), and peptide-modified systems, as well as their stimulus-responsive mechanisms across exogenous light, microenvironmental, and organelle-targeted delivery. Furthermore, we highlight synergistic therapeutic strategies combining CO gas therapy with photothermal, photodynamic, chemodynamic, and immunotherapy under NIR-II guidance, demonstrating enhanced therapeutic efficacy while minimizing systemic toxicity. Despite these advances, significant challenges remain, including the lack of subcellular-level CO monitoring, incomplete synergy between NIR-II imaging and CO bioactivity, and hurdles in clinical translation. This review aims to provide critical insights into the rational design of NIR-II-guided CO nanodelivery systems, offering a blueprint for their future development towards precise, safe, and effective disease treatment.