Microenvironment-Activatable Long-Wavelength NIR-II Visualization and Synergistic Treatment of Pulmonary Embolism
Abstract
Pulmonary embolism (PE) is a life-threatening thrombotic condition, yet its precise diagnosis and effective treatment remain a major clinical challenge. In this study, we report the development of a microenvironment-activatable nanoplatform that enables hypoxia-triggered long-wavelength second near-infrared (NIR-II) fluorescence imaging for accurate thrombus visualization, combined with photothermal therapy (PTT) and controlled hydrogen sulfide (H 2 S) release for synergistic therapeutic intervention. We first synthesize an N -oxide-based molecular probe that undergoes hypoxia-induced structural transition, thereby activating both NIR-II fluorescence and photothermal properties. This probe, together with a thermosensitive H 2 S donor, is encapsulated into nanoparticles, which are further functionalized with bis-serotonin groups to achieve thrombus-specific targeting via the myeloperoxidase and hydrogen peroxide-mediated aggregation. In a PE mouse model, the nanoagent enables highly selective and sensitive visualization of thrombi via activatable NIR-II fluorescence imaging after intravenous injection, achieving a remarkable signal-to-noise ratio exceeding 120. The combined PTT and H 2 S therapy significantly enhance thrombolytic efficacy compared to conventional treatment (e.g., urokinase). Importantly, the nanoagent exhibits excellent biocompatibility in vivo, with minimal risk of hemorrhagic complications. This high-performance hypoxia-responsive platform offers a promising strategy for the precise diagnosis and effective treatment of PE and other cardiovascular diseases.
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Upon irradiation, 5SGNPs elevated the lung surface temperature to approximately 42 °C within 10 min.
“Upon irradiation, 5SGNPs elevated the lung surface temperature to ~42 °C within 10 min.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [236]
5SGNPs tend to form large aggregates through reaction between surface bis-5HT and myeloperoxidase, achieving selective targeting to thrombus sites.
“Notably, 5SGNPs tended to form large aggregates through the reaction between surface bis-5HT and myeloperoxidase (MPO), thereby achieving selective targeting to thrombus sites.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [236]
5SGNPs demonstrate hypoxia-induced photothermal effects with a PCE of 39% and H2S release capability upon 808 nm laser irradiation.
“Furthermore, 5SGNPs demonstrated hypoxia-induced photothermal effects (with PCE of 39%) and H2S release capability upon 808 nm laser irradiation.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [236]
In PE mice, pulmonary accumulation of 5SGNPs peaked at 2 h post-administration, accompanied by strong NIR-II fluorescence signals with an SNR of 124.
“In PE mice, pulmonary accumulation of 5SGNPs peaked at 2 h post-administration, accompanied by strong NIR-II fluorescence signals with SNR of 124.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [236]
Compared to free urokinase, the 5SGNPs nanosystem achieved rapid and efficient thrombus degradation by combining PTT with H2S release.
“Compared to free urokinase (UK), this nanosystem achieved rapid and efficient thrombus degradation by combining PTT with H2S release.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [236]
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Organic small-molecule NIR-II fluorophores for tumor phototheranostics
Xiang, D., Wang, Z., Zheng, H., Tang, Y., & Li, Q. (2026) · Light: Science & Applications · doi:10.1038/s41377-026-02212-w · Cited by 22 · see citing works
“23c) 236 .”
- Authors
- Meng, X., Song, J., Du, Z., Tao, Y., & Qi, J.
- Affiliations
- Nankai University (CN)
- Corresponding author
- Qi, Ji
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2025-06-11
- Volume
- 19
- Issue
- 24
- Pages
- 22454-22467
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W4411200709
- Cited by
- 18
- References
- 51
- Citations by year
- 2026: 14 · 2025: 4
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Nankai University
- Tianjin Municipal Science and Technology Program (24ZXZSSS00270)
- Fundamental Research Funds for the Central Universities (63253263)
- National Natural Science Foundation of China (32471462, 82172081, 824B2057)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Keywords
- pulmonary embolism, NIR-II fluorescence imaging, photothermal therapy, hydrogen sulfide release, thrombus visualization, thrombolysis, urokinase
- MeSH terms
- Photothermal Therapy, Animals, Fluorescent Dyes, Humans, Hydrogen Sulfide, Infrared Rays, Pulmonary Embolism, Mice, Nanoparticles, Optical Imaging
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