On-Chip Microfluidic Production of Sonosensitizer-Loaded Liposomes for Sonodynamic Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths worldwide. Among the emerging therapies, ultrasound-mediated sonosensitizers have shown promise in the treatment of HCC. Sonosensitizers exposed to low-intensity ultrasound energy can generate reactive oxygen species (ROS), which can lead to cancer cell death. Indocyanine green (ICG) is a commonly used sonosensitizer that can be used for treating HCC. However, ICG has a short half-life and needs a carrier to improve its therapeutic efficacy. Herein, we report the development of ICG-loaded liposomes with controlled size distribution using a simple one-step microfluidic device-based strategy. We evaluated the stability of ICG-loaded liposomes (lipo-ICG) by subjecting them to various storage conditions. The designed lipo-ICGs are stable and capable of inducing liver cancer cell death (HepG2 cells) upon ultrasound exposure. Last but not least, the designed lipo-ICGs are cytocompatible to both cancerous (HepG2 cells) and noncancerous cells (HHSteC) without ultrasound exposures. Taken together, our findings highlight the potential of this microfluidic platform for the efficient production of lipo-ICG nanoparticles and demonstrate the promise of ultrasound-mediated therapy as a targeted, minimally invasive strategy for treating HCC.