Ultrasound Trigger Ultrasmall Multifunction Nanobubbles for Thrombus Visual Treatment

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Current thrombolytic drug delivery faces limitations due to hemorrhagic risks and the pro-inflammatory thrombus microenvironment.
• There is a need for advanced therapeutic strategies that offer visualized treatment and mitigate adverse effects.

Purpose of the Study:

• To design and evaluate an ultrasmall nanobubble (CeO2/MnOx@UK@PFP) for integrated imaging and therapy of thrombotic disease.
• To achieve visualized thrombolysis and adjust the thrombus microenvironment by targeted delivery of Urokinase (UK) and reactive oxygen species (ROS) scavenging agents.

Main Methods:

• Preparation of CeO2/MnOx nanoparticles with ROS scavenging activity, encapsulated with UK and perfluoropentane (PFP) within a lipid layer.
• Utilizing low-intensity pulsed ultrasound (LIPUS) to trigger PFP phase transition for real-time ultrasound imaging and nanobubble rupture, releasing therapeutic agents.
• In vitro and in vivo experiments to assess thrombolysis efficiency, imaging capabilities, anti-inflammatory effects, and ROS scavenging activity.

Main Results:

• The CeO2/MnOx@UK@PFP nanobubble system enabled real-time ultrasound imaging of thrombolytic treatment progression.
• LIPUS triggered the release of UK and CeO2/MnOx, facilitating targeted thrombolysis and reducing hemorrhagic risk.
• The nanobubbles demonstrated significant ROS scavenging and anti-inflammatory properties, protecting the endangium.

Conclusions:

• The developed CeO2/MnOx@UK@PFP nanobubble system offers a promising approach for visualized thrombolysis with enhanced safety and efficacy.
• This integrated imaging and therapeutic strategy effectively addresses the limitations of conventional thrombolytic treatments.