EFFECT OF MOLECULAR WEIGHT ON SONOPORATION-MEDIATED UPTAKE IN HUMAN CELLS

被引：18

作者：

Bhutto, Danyal F. ^{[1
]}

Murphy, Emily M. ^{[1
]}

Priddy, Mariah C. ^{[1
]}

Centner, Connor C. ^{[1
]}

Moore, Joseph B. ^{[2
]}

Bolli, Roberto ^{[2
]}

Kopechek, Jonathan A. ^{[1
,2
]}

机构：

[1] Univ Louisville, Dept Bioengn, Louisville, KY 40292 USA

[2] Univ Louisville, Inst Mol Cardiol, Dept Med, Louisville, KY 40292 USA

来源：

ULTRASOUND IN MEDICINE AND BIOLOGY | 2018年 / 44卷 / 12期

基金：

美国国家卫生研究院;

关键词：

Ultrasound; Microbubbles; Sonoporation; Drug delivery; Fluorescein isothiocyanate-dextran; Cardiac cells; Cancer cells; TARGETED MICROBUBBLE DESTRUCTION; CARDIAC GENE DELIVERY; LOCAL-DELIVERY; ULTRASOUND; CANCER; DRUG; TRANSFECTION; THERAPEUTICS; TRANSPORT; SIRNA;

D O I：

10.1016/j.ultrasmedbio.2018.08.008

中图分类号：

O42 [声学];

学科分类号：

070206 ; 082403 ;

摘要：

Ultrasound-induced microbubble destruction can enhance drug delivery to cells. The molecular weight of therapeutic compounds varies significantly (from <1 kDa for small molecule drugs, to 7-15 kDa for siRNAs/miRNAs, to >1000 kDa for DNA plasmids). Therefore, the objective of this study was to determine the relationship between uptake efficiency and molecular weight using equal molar concentrations. Uptake efficiency of fluorescent compounds with different molecular weights (0.3, 10 and 2000 kDa) was explored in vitro using human cardiac mesenchymal cells and breast cancer cells exposed to microbubbles and 2.5-MHz ultrasound pulses. Uptake by viable cells was quantified using flow cytometry. After correction for the fluorescence yield of each compound, there was a significant size-dependent difference in fluorescence intensity, indicating an inverse relationship between size and uptake efficiency. These results suggest that diffusion of therapeutic compounds across permeabilized cell membranes may be an important mechanism for ultrasound-mediated drug delivery. (C) 2018 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

引用

页码：2662 / 2672

页数：11

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