title: A continuous tri-phase transition effect for HIFU-mediated intravenous drug delivery.
abstract: Aiming at substantially enhanced efficacy and biosafety of clinical HIFU therapy, a natural solid medium, L-menthol (LM), characteristic of mild and controllable "solid-liquid-gas" (SLG) tri-phase transition, was adopted, instead of those conventional explosive liquid-gas (LG) bi-phase transitional media, in constructing a multifunctional theranostic system. Owing to the continuous and controllable characteristics of SLG tri-phase transition, such a novel tri-phase transition-based theranostic system has been demonstrated of the repeatedly enhanced HIFU efficacy ex vivo and in vivo under once intravenous injection and the significantly improved treatment precision, controllability and biosafety when comparing to the traditional bi-phase transition medium, perfluorohexane (PFH), thus promising great application potential in clinical HIFU treatment. Moreover, this theranostic system has been demonstrated a long blood-circulation lifetime and continuous accumulation in tumor in 24 h, which is very beneficial for the enhanced tumor ablation in vivo along with SLG tri-phase transition. More importantly, after loading multiple model drugs and real drug, such a theranostic system presents a HIFU-mediated temperature-responsive drug release property, and depending on the versatile miscibility of LM, co-loadings with hydrophobic and hydrophilic drugs are also achieved, which provides the possibility of synergistic treatment combining HIFU therapy and chemotherapy.
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, PR China. Electronic address: hrchen@mail.sic.ac.cn.
authors.forename: Hangrong
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Faqi
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Tenth Peoples Hospital of Tongji University, Shanghai 200072, PR China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Tenth Peoples Hospital of Tongji University, Shanghai 200072, PR China.
authors.forename: Huixiong
authors.initials: H
authors.lastname: Xu
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, PR China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Jia
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Mou
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, PR China. Electronic address: jlshi@sunm.shcnc.ac.cn.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Shi
mesh_terms: D000818:Animals; D002417:Cattle; D002470:Cell Survival; D004396:Coloring Agents / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000628:therapy*; D044367:Phase Transition; D011817:Rabbits
chemical_list: D004396:Coloring Agents
keywords: Continuous ultrasound imaging; HIFU-mediated drug delivery; Repeated HIFU treatment; Tri-phase transition