Intracellular drug delivery using low-frequency ultrasound:: Quantification of molecular uptake and cell viability
Intracellular drug delivery using low-frequency ultrasound:: Quantification of molecular uptake and cell viability
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DOI：
10.1023/a:1013066027759
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发表时间：
2001-11-01
影响因子：
3.7
通讯作者：
Prausnitz, MR
中科院分区：
文献类型：
--
作者：
Keyhani, K;Guzmán, HR;Prausnitz, MR
目的.为了确定依赖于声学参数的分子吸收和细胞活力暴露于低频超声。将浸泡在钙黄绿素溶液中的DU 145前列腺癌细胞在不同声压、暴露时间、脉冲长度和占空比的范围内暴露于24 kHz的超声。流式细胞术定量检测钙黄绿素分子进入细胞的数量和细胞活力水平。分子摄取和细胞活力均表现出对声压和暴露时间的强依赖性，对脉冲长度的弱依赖性，并且对占空比没有显著依赖性。当所有数据汇总在一起时，它们与声能暴露表现出良好的相关性。虽然分子摄取显示出大的细胞间异质性，高达15%的细胞达到细胞内钙黄绿素浓度约等于其细胞外浓度。大量的分子可以使用低频超声在细胞内递送。摄取和活力都与声能相关，这对于超声方案的设计和控制是有用的。
Purpose. To determine the dependence on acoustic parameters of molecular uptake and viability of cells exposed to low-frequency ultrasound.Methods. DU145 prostate cancer cells bathed in a solution of calcein were exposed to ultrasound at 24 kHz over a range of different acoustic pressures, exposure times, pulse lengths, and duty cycles. Flow cytometry was employed to quantify the number of calcein molecules delivered into each cell and levels of cell viability.Results. Both molecular uptake and cell viability showed a strong dependence on acoustic pressure and exposure time, weak dependence on pulse length, and no significant dependence on duty cycle. When all of the data were pooled together, they exhibited good correlation with acoustic energy exposure. Although molecular uptake showed large cell-to-cell heterogeneity, up to similar to 15% of cells achieved an intracellular calcein concentration approximately equal to its extracellular concentration.Conclusions. Large numbers of molecules can be delivered intracellularly using low-frequency ultrasound. Both uptake and viability correlate with acoustic energy, which is useful for design and control of ultrasound protocols.