Novel biomimetic dual-mode nanodroplets as ultrasound contrast agents with potential ability of precise detection and photothermal ablation of tumors

Purpose: Molecule-targeted ultrasound imaging has attracted extensive attention for precise diagnosis and targeted therapy of tumors. The aim of this research is to prepare novel biomimetic dual-mode nanoscale ultrasound contrast agents (UCAs), which can not only evade the immune clearance of reticuloendothelial system, but also have the potential ability of precise detection and photothermal ablation of tumors. Methods: In this study, for the first time, the novel biomimetic UCAs were prepared by encapsulating liquid perfluorohexanes with red blood cell membranes carrying IR-780 iodide and named IR780-RBCM@NDs. The characteristics of that were verified through the particle size analyzer, scanning electron microscopy, transmission electron microscopy and laser scanning confocal microscopy. The stability of IR780-RBCM@NDs at 37 °C was explored. The abilities of immune escape, dual-mode imaging and photothermal effect for IR780-RBCM@NDs were verified via in vitro experiments. Results: The novel prepared nanodroplets have good characteristics such as mean diameter, zeta potential, and relatively stability. Importantly, the integrin-associated protein expressed on the surface of RBCMs was detected on IR780-RBCM@NDs. Then, compared with control groups, IR780-RBCM@NDs performed excellent immune escape function away from macrophages in vitro. Furthermore, the IR-780 iodide was observed on the new nanodroplets and that was able to perform the dual-mode imaging with near-infrared fluorescence imaging and contrast-enhanced ultrasound imaging after the phase change. Finally, the effective photothermal ablation ability of IR780-RBCM@NDs was verified in tumor cells. Conclusion: The newly prepared biomimetic IR780-RBCM@NDs provided novel ideas for evading immune clearance, performing precise diagnosis and photothermal ablation of tumor cells.