Microenvironment-Activatable Long-Wavelength NIR-II Visualization and Synergistic Treatment of Pulmonary Embolism

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Pulmonary embolism (PE) presents diagnostic and therapeutic challenges.
• Accurate thrombus visualization and effective treatment are critical.
• Current treatments for PE have limitations.

Purpose of the Study:

• To develop a microenvironment-activatable nanoplatform for PE diagnosis and treatment.
• To enable hypoxia-triggered NIR-II fluorescence imaging for thrombus visualization.
• To combine photothermal therapy (PTT) and hydrogen sulfide (H2S) release for synergistic thrombolysis.

Main Methods:

• Synthesis of an N-oxide-based molecular probe activating NIR-II fluorescence and photothermal properties under hypoxia.
• Encapsulation of the probe and a thermosensitive H2S donor into nanoparticles.
• Functionalization of nanoparticles with bis-serotonin for thrombus-specific targeting.
• Evaluation in a pulmonary embolism mouse model using NIR-II imaging and combined PTT/H2S therapy.

Main Results:

• The nanoagent achieved highly selective and sensitive thrombus visualization via activatable NIR-II fluorescence imaging.
• A signal-to-noise ratio exceeding 120 was obtained in a PE mouse model.
• Combined PTT and H2S therapy significantly enhanced thrombolytic efficacy compared to urokinase.
• The nanoagent demonstrated excellent in vivo biocompatibility with minimal hemorrhagic risk.

Conclusions:

• The hypoxia-responsive nanoplatform offers a promising strategy for precise PE diagnosis.
• The combined therapeutic approach (PTT and H2S release) shows enhanced thrombolytic efficacy.
• This platform holds potential for treating PE and other cardiovascular diseases.