High-intensity focused ultrasound-triggered nanoscale bubble-generating liposomes for efficient and safe tumor ablation under photoacoustic imaging monitoring

Abstract

Gang Feng,1 Lan Hao,1 Chunyan Xu,1 Haitao Ran,1 Yuanyi Zheng,1 Pan Li,1 Yang Cao,1 Qi Wang,2 Jizhu Xia,1 Zhigang Wang1 1Department of Ultrasound, Institute of Ultrasound Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, 2State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Chongqing, People’s Republic of China Abstract: High-intensity focused ultrasound (HIFU) is widely applied to tumors in clinical practice due to its minimally invasive approach. However, several issues lower therapeutic efficiency in some cases. Many synergists such as microbubbles and perfluorocarbon nanoparticles have recently been used to improve HIFU treatment efficiency, but none were determined to be effective and safe in vivo. In this study, nanoscale bubble-generating liposomes (liposomes containing ammonium bicarbonate [Lip-ABC]) were prepared by film hydration followed by sequential extrusion. Their stable nanoscale particle diameter was confirmed, and their bubble-generating capacity after HIFU triggering was demonstrated with ultrasound imaging. Lip-ABC had good stability in vivo and accumulated in the tumor interstitial space based on the enhanced permeability and retention effect evaluated by photoacoustic imaging. When used to synergize HIFU ablation to bovine liver in vitro and implanted breast tumors of BALB/c nude mice, Lip-ABC outperformed the control. Importantly, all mice survived HIFU treatment, suggesting that Lip-ABC is a safe HIFU synergist. Keywords: HIFU, nanoscale bubble-generating liposomes, efficiency, synergize

Keywords

• HIFU
• nanoscale bubble-generating liposomes
• efficiency
• synergize