Can ultrasound enable efficient intracellular uptake of molecules? A retrospective literature review and analysis.
Can ultrasound enable efficient intracellular uptake of molecules? A retrospective literature review and analysis.
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DOI：
10.1016/j.ultrasmedbio.2012.01.006
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发表时间：
2012-05
影响因子：
2.9
通讯作者：
Prausnitz, Mark R.
中科院分区：
文献类型：
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作者：
Liu, Ying;Yan, Jing;Prausnitz, Mark R.
大多数用于细胞内递送药物、蛋白质、DNA/RNA 和其他化合物的治疗超声 (US) 应用将受益于将这些分子有效摄取到大量细胞中，而在此过程中不会杀死细胞。在这项研究中，我们测试了这样的假设：在体外超声暴露后，可以实现分子的有效细胞内摄取和高细胞活力。检索文献以查找有关摄取和活力的定量数据的研究，得出 26 篇发表的论文，其中包含 898 个实验数据点。对这些研究的分析表明，只有 7.7% 的数据点对应于相对有效的摄取（> 50% 的细胞表现出摄取）。对数据的仔细检查表明，使用 Definity US 造影剂（而不是 Optison）和 37°C 升高超声处理温度（而不是室温）与高摄取相关，我们通过本研究中进行的独立实验进一步验证了这一点。尽管这些因素导致了高摄取，但几乎所有有效摄取的数据都来自在确定细胞活力时未考虑裂解细胞的研究。基于对数据的回顾性分析，我们表明，不考虑裂解细胞可以显着提高计算的吸收效率。我们进一步认为，如果重新分析本研究中考虑的所有数据以解释裂解细胞，则基本上不会有有效吸收的数据。因此，我们得出的结论是，文献并不支持这样的假设：在体外暴露US后可以实现分子的有效细胞内摄取并具有高细胞活力，这对需要有效细胞内递送的US的未来应用提出了挑战。
Most applications of therapeutic ultrasound (US) for intracellular delivery of drugs, proteins, DNA/ RNA and other compounds would benefit from efficient uptake of these molecules into large numbers of cells without killing cells in the process. In this study we tested the hypothesis that efficient intracellular uptake of molecules can be achieved with high cell viability after US exposure in vitro. A search of the literature for studies with quantitative data on uptake and viability yielded 26 published papers containing 898 experimental data points. Analysis of these studies showed that just 7.7% of the data points corresponded to relatively efficient uptake (>50% of cells exhibiting uptake). Closer examination of the data showed that use of Definity US contrast agent (as opposed to Optison) and elevated sonication temperature at 37°C (as opposed to room temperature) were associated with high uptake, which we further validated through independent experiments carried out in this study. Although these factors contributed to high uptake, almost all data with efficient uptake were from studies that had not accounted for lysed cells when determining cell viability. Based on retrospective analysis of the data, we showed that not accounting for lysed cells can dramatically increase the calculated uptake efficiency. We further argue that if all the data considered in this study were re-analyzed to account for lysed cells, there would be essentially no data with efficient uptake. We therefore conclude that the literature does not support the hypothesis that efficient intracellular uptake of molecules can be achieved with high cell viability after US exposure in vitro, which poses a challenge to future applications of US that require efficient intracellular delivery.
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影响因子：
2.4
作者：
Guzmán, HR;Nguyen, DX;Prausnitz, MR
通讯作者：
Prausnitz, MR
影响因子：
5.1
作者：
Azuma, H;Tomita, N;Morishita, R
通讯作者：
Morishita, R
影响因子：
2.9
作者：
Karshafian, Raffi;Bevan, Peter D.;Burns, Peter N.
通讯作者：
Burns, Peter N.
DOI：
10.7863/jum.2011.30.1.61
发表时间：
2011-01
期刊：
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
影响因子：
--
作者：
Forbes MM;Steinberg RL;O'Brien WD Jr
通讯作者：
O'Brien WD Jr
影响因子：
38.3
作者：
通讯作者：
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