Targeted and ultrasound-triggered cancer cell injury using perfluorocarbon emulsion-loaded liposomes endowed with cancer cell-targeting and fusogenic capabilities

• Emulsion of perfluoropentane (ePFC5)-loaded liposomes were sensitive to ultrasound.
• Liposomes modified with avidin (avidin liposomes) recognized cancer cells.
• Liposomes modified with fusogenic protein (HVJ liposomes) fused to cancer cells.
• ePFC5-loaded avidin/HVJ liposomes were internalized directly into cancer cells.
• Cancer cell viability was 43% with ultrasound and ePFC5-loaded avidin/HVJ liposomes.

This study investigated the targeting and ultrasound-triggered injury of cancer cells using anticancer drug-free liposomes that contained an emulsion of perfluoropentane (ePFC5) and were co-modified with avidin as a targeting ligand for cancer cells and the hemagglutinating virus of Japan (HVJ) envelope to promote liposome fusion with the cells. These liposomes are designated as ePFC5-loaded avidin/HVJ liposomes. ePFC5-loaded liposomes were sensitized to ultrasound irradiation. Liposomes modified with avidin alone (avidin liposomes) showed binding to MCF-7 human breast cancer cells, and liposomes modified with HVJ envelope alone (HVJ liposomes) were found to fuse with MCF-7 cells. The irradiation of MCF-7 cells with 1 MHz ultrasound (30 s, 1.2 W/cm2, duty ratio 30%) combined with ePFC5-loaded avidin/HVJ liposomes resulted in a decrease in cell viability at 1 h after irradiation to 43% of that of controls without ultrasound irradiation or liposomes. The cell viability was lower than that of cells treated with ultrasound irradiation with ePFC5-loaded avidin liposomes or ePFC5-loaded HVJ liposomes. This indicates that co-modification of liposome with avidin and HVJ envelope could enhance ultrasound-induced cell injury in the presence of ePFC5-loaded liposomes.