Evaluation of perfluoropropane (CF)-filled chitosan polyacrylic acid nanobubbles for ultrasound imaging of sentinel lymph nodes and tumors

Accurate sentinel lymph node (SLN) identification is an important prerequisite for sentinel lymph node biopsy (SLNB). However, existing SLN mapping techniques, mainly imaging-guided methods, are severely restricted by the high cost of the instruments, harmful radiation or unsatisfactory imaging depths. Herein, we prepared a new ultrasound contrast agent by filling perfluoropropane (C 3 F 8 ) into chitosan polyacrylic acid nanobubbles for precise SLN identification. The obtained ultrasound contrast agent, coined C 3 F 8 -CS-PAA nanobubbles, presents a nanometer size with a diameter of approximately 120 nm. The C 3 F 8 -CS-PAA nanobubbles of desirable size are able to enter lymphatic vessels and accumulate in the sentinel lymph node to enhance ultrasound imaging. As a result, the injection of C 3 F 8 -CS-PAA nanobubbles can remarkably enhance the ultrasound imaging lymph system, providing image guidance for sentinel lymph node biopsy. Furthermore, it was shown that such C 3 F 8 -CS-PAA nanobubbles can effectively permeate into the tumor region via the tumor-enhanced permeability and retention (EPR) effect to enhance tumor ultrasound imaging for monitoring tumorigenesis. This work highlights a novel nanoscale ultrasound contrast agent for the lymphatic system and tumor imaging, with great promise for subsequent studies and clinical applications. The synthetic procedure of C 3 F 8 -CS-PAA nanobubbles for CEUS imaging.