title: A Disposable Microfluidic Device for Controlled Drug Release from Thermal-Sensitive Liposomes by High Intensity Focused Ultrasound.
abstract: The drug release triggered thermally by high intensity focused ultrasound (HIFU) has been considered a promising drug delivery strategy due to its localized energy and non-invasive characters. However, the mechanism underlying the HIFU-mediated drug delivery remains unclear due to its complexity at the cellular level. In this paper, micro-HIFU (MHIFU) generated by a microfluidic device is introduced which is able to control the drug release from temperature-sensitive liposomes (TSL) and evaluate the thermal and mechanical effects of ultrasound on the cellular drug uptake and apoptosis. By simply adjusting the input electrical signal to the device, the temperature of sample can be maintained at 37 °C, 42 °C and 50 °C with the deviation of ± 0.3 °C as desired. The flow cytometry results show that the drug delivery under MHIFU sonication leads to a significant increase in apoptosis compared to the drug release by incubation alone at elevated temperature of 42 °C. Furthermore, increased squamous and protruding structures on the surface membrane of cells were detected by atomic force microscopy (AFM) after MHIFU irradiation of TSL. We demonstrate that compared to the routine HIFU treatment, MHIFU enables monitoring of in situ interactions between the ultrasound and cell in real time. Furthermore, it can quantitatively analyze and characterize the alterations of the cell membrane as a function of the treatment time.
authors.affiliation: 1. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedicaland Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P.R. China, 518055.
authors.forename: Long
authors.initials: L
authors.lastname: Meng
authors.affiliation: 1. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedicaland Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P.R. China, 518055.
authors.forename: Zhiting
authors.initials: Z
authors.lastname: Deng
authors.affiliation: 1. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedicaland Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P.R. China, 518055.
authors.forename: Lili
authors.initials: L
authors.lastname: Niu
authors.affiliation: 1. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedicaland Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P.R. China, 518055.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: 1. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedicaland Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P.R. China, 518055.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.affiliation: 2. Department of Physics, University of Vermont, USA.
authors.forename: Junru
authors.initials: J
authors.lastname: Wu
authors.affiliation: 1. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedicaland Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P.R. China, 518055.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Cai
authors.affiliation: 1. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedicaland Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P.R. China, 518055.
authors.forename: Hairong
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D004209:Disposable Equipment; D016503:Drug Delivery Systems; D065546:Drug Liberation; D056656:Lab-On-A-Chip Devices; D008081:Liposomes / Q000008:administration & dosage* / Q000528:radiation effects*; D051379:Mice; D018625:Microscopy, Atomic Force; D013696:Temperature; D014465:Ultrasonics / Q000379:methods*
chemical_list: D008081:Liposomes
keywords: high intensity focused ultrasound; mechanical and thermal effects; microfluidics; ultrasound-mediated drug delivery