Enhanced HIFU Theranostics with Dual-Frequency-Ring Focused Ultrasound and Activatable Perfluoropentane-Loaded Polymer Nanoparticles
Junjie Chen,
Zhezhu Nan,
Yubo Zhao,
Lei Zhang,
Hongrui Zhu,
Daocheng Wu,
Yujin Zong,
Mingzhu Lu,
Tali Ilovitsh,
Mingxi Wan,
Kai Yan,
Yi Feng
Affiliations
Junjie Chen
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
Zhezhu Nan
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
Yubo Zhao
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
Lei Zhang
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
Hongrui Zhu
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
Daocheng Wu
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
Yujin Zong
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
Mingzhu Lu
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
Tali Ilovitsh
Department of Biomedical Engineering, Tel Aviv University, Tel Aviv 6997801, Israel
Mingxi Wan
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
Kai Yan
College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China
Yi Feng
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi′an Jiaotong University, Xi′an 710049, China
High-intensity focused ultrasound (HIFU) has been widely used in tumor ablation in clinical settings. Meanwhile, there is great potential to increase the therapeutic efficiency of temporary cavitation due to enhanced thermal effects and combined mechanical effects from nonlinear vibration and collapse of the microbubbles. In this study, dual-frequency (1.1 and 5 MHz) HIFU was used to produce acoustic droplet vaporization (ADV) microbubbles from activatable perfluoropentane-loaded polymer nanoparticles (PFP@Polymer NPs), which increased the therapeutic outcome of the HIFU and helped realize tumor theranostics with ultrasound contrast imaging. Combined with PFP@Polymer NPs, dual-frequency HIFU changed the shape of the damage lesion and reduced the acoustic intensity threshold of thermal damage significantly, from 216.86 to 62.38 W/cm2. It produced a nearly 20 °C temperature increase in half the irradiation time and exhibited a higher tumor inhibition rate (84.5% ± 3.4%) at a low acoustic intensity (1.1 MHz: 23.77 W/cm2; 5 MHz: 0.35 W/cm2) in vitro than the single-frequency HIFU (60.2% ± 11.9%). Moreover, compared with the traditional PFP@BSA NDs, PFP@Polymer NPs showed higher anti-tumor efficacy (81.13% vs. 69.34%; * p p < 0.0001), probably benefitting from its uniform and stable structure. It showed potential as a highly efficient tumor theranostics approach based on dual-frequency HIFU and activatable PFP@Polymer NPs.
