These lipid-shelled microbubbles encapsulate perfluorobutane gas and embed protoporphyrin IX within a DSPC/DSPE-PEG2000 lipid monolayer. They are fabricated by forming PpIX-laden liposomes via thin-film hydration, followed by agitation with perfluorocarbon gas and surfactant to produce bubbles of defined size and drug load, quantified by fluorescence and particle sizing. Following administration into cell suspensions or tumor tissue, pulsed ultrasound (1 MHz, 10% duty cycle) delivered by flat, focused or steerable array transducers triggers local ROS generation. Progress is monitored through real-time 3D ultrasound imaging using contrast pulse sequencing, while in vitro ROS assays, cytotoxicity tests and in vivo murine tumor studies confirm targeted anticancer efficacy.
Description
This approach distinguishes itself through precise incorporation of hydrophobic sonosensitizers into the lipid shell of stable perfluorobutane microbubbles, enabling controlled cavitation-mediated ROS release only upon acoustic activation. The use of steerable ultrasound arrays and mechanical scanning expands treatment volumes, while intermittent pulsing allows microbubble reperfusion for sustained therapy. Coupling therapeutic delivery with high-resolution contrast imaging ensures accurate dose localization and real-time response assessment. Tight control over fabrication parameters and a modular design support reproducible, scalable production, resulting in superior targeted cytotoxicity compared to free or liposomal sensitizers and minimizing off-target effects.
Applications
- Targeted sonodynamic cancer therapy
- Ultrasound-triggered drug delivery
- Contrast-enhanced ultrasound imaging
- Non-invasive tumor ablation
- Intravenous sonodynamic therapy
Advantages
- Ultrasound-triggered, localized reactive oxygen species generation for precise tumor cell killing
- Integrated diagnostic and therapeutic (“theranostic”) capability through contrast-enhanced 3D ultrasound imaging
- High-capacity, stable loading of hydrophobic sonosensitizers in lipid-shelled microbubbles for efficient delivery
- Minimally invasive administration (intravenous or intratumoral) with noninvasive, externally controlled activation
- Customizable ultrasound parameters and beam steering enable precise dosing and treatment of tumors of varying size
IP Status
https://patents.google.com/patent/WO2019050963A1
