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

## TL;DR

This paper reviews how near-infrared imaging helps control carbon monoxide delivery for precise disease treatment, combining imaging with therapy to improve effectiveness and safety.

## Contribution

The paper provides a comprehensive review of NIR-II-guided CO nanomedicine design and therapies, emphasizing multimodal synergies and clinical translation challenges.

## Key findings

- NIR-II imaging enables precise CO delivery with high resolution and deep tissue penetration.
- CO nanomedicine combined with photothermal and immunotherapy shows enhanced therapeutic efficacy.
- Challenges include subcellular CO monitoring and synergy between imaging and CO bioactivity.

## Abstract

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.

This review summarizes recent advances in near-infrared II (NIR-II)-guided carbon monoxide (CO) nanomedicine, emphasizing design strategies, stimuli-responsive delivery, and synergistic therapies. It highlights how NIR-II imaging enables precise, controllable CO release with enhanced therapeutic efficacy and reduced toxicity, while outlining key challenges and future directions toward clinical translation.Image 1