Journal
THERANOSTICS
Volume 5, Issue 11, Pages 1203-1213Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.12295
Keywords
ultrasound-mediated drug delivery; high intensity focused ultrasound; mechanical and thermal effects; microfluidics
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Funding
- 973 Program [2015CB755500]
- National Natural Science Foundation of China [11304341, 11302239, 11274008, 81401435, 11325420]
- Guangdong Research Grant [S2013040014610]
- Shenzhen Basic Science Research [JCYJ20140417113430580, JCYJ20130402113127516]
- Shenzhen Key Laboratory of Nanobiomechanics
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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 degrees C, 42 degrees C and 50 degrees C with the deviation of +/- 0.3 degrees 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 degrees 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.
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