Lipid Shell Retention and Selective Binding Capability Following Repeated Transient Acoustic Microdroplet Vaporization.
Lipid Shell Retention and Selective Binding Capability Following Repeated Transient Acoustic Microdroplet Vaporization.
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DOI：
10.1021/acs.langmuir.0c00320
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发表时间：
2020-06-23
期刊：
影响因子：
3.9
通讯作者：
Bull, Joseph L.
中科院分区：
文献类型：
--
作者：
Harmon, Jonah S.;Celingant-Copie, Chloe A.;Kabinejadian, Foad;Bull, Joseph L.
使用微泡造影剂进行超声靶向治疗和分子成像已经得到了广泛的探索，最近，当暴露于聚焦超声时蒸发的可活化的液滴造影剂也得到了探索。这些液滴被一层稳定的、可功能化的外壳包裹着，外壳通常由完全饱和的磷脂组成。虽然超声暴露下脂质外壳的脱落在微泡中是一个被充分研究的现象，但在液滴型造影剂中尚未得到充分研究，特别是在那些经历可逆相变和蒸发后再凝聚的造影剂中。在这里，我们研究了脂质壳在重复瞬态汽化事件后的保留。两种单独的荧光标记被用于跟踪单个脂质亚群：聚乙二醇化脂质，靶向配体通常与之结合，非聚乙二醇化脂质，主要有助于液滴的稳定性。在使用共聚焦显微镜确认每个壳脂亚群的均匀表面分布之后，高速光学成像提供了视觉证据，证明使用从成像换能器传输的5.208 MHz， 3.17 MPa聚焦超声脉冲，可以反复诱导微米级液滴的蒸发和再凝结。流式细胞术分析表明，在反复的瞬态相变事件后，聚乙二醇化的脂质被完全保留，20%的散装脂质脱落。虽然这可能导致了平均液滴直径的显著减小，但靶向整合素αvβ3的RGD肽功能化液滴的选择性结合能力并未受到影响。这些结果表明，重复的液滴激活可能会促进液滴大小分布的变化，但不会影响靶向治疗或分子成像的准确性。
Targeted therapy and molecular imaging using ultrasound have been widely explored using microbubble contrast agents, and more recently, activatable droplet contrast agents that vaporize when exposed to focused ultrasound have been explored. These droplets are coated with a stabilizing, functionalizable shell, typically comprised of fully saturated phospholipids. While the shedding of the lipid shell under ultrasound exposure is a well-studied phenomenon in microbubbles, it has not been fully explored in droplet-based contrast agents, particularly in those that undergo a reversible phase change and recondense following vaporization. Here, we investigate the retention of the lipid shell following repeated transient vaporization events. Two separate fluorescent markers were used to track individual lipid subpopulations: PEGylated lipids, to which targeting ligands are typically bound, and non-PEGylated lipids, which primarily contribute to droplet stability. Following confirmation of the homogeneous surface distribution of each subpopulation of shell lipids using confocal microscopy, high-speed optical imaging provided visual evidence of the ability to repeatedly induce vaporization and recondensation in micron-scale droplets using 5.208 MHz, 3.17 MPa focused ultrasound pulses transmitted from an imaging transducer. Flow cytometry analysis indicated that while PEGylated lipids were fully retained following repeated transient phase change events, 20% of the bulk lipids were shed. While this likely contributed to an observed significant reduction in the average droplet diameter, the selective binding capabilities of droplets functionalized with an RGD peptide, targeted to the integrin αvβ3, were not affected. These results indicate that repeated droplet activation may promote shifts in the droplet size distribution but will not influence the accuracy of targeting for therapy or molecular imaging.
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影响因子：
10.8
作者：
Li DS;Yoon SJ;Pelivanov I;Frenz M;O'Donnell M;Pozzo LD
通讯作者：
Pozzo LD
影响因子：
10.8
作者：
Li DS;Schneewind S;Bruce M;Khaing Z;O'Donnell M;Pozzo L
通讯作者：
Pozzo L
影响因子：
3.7
作者：
Fabiilli, Mario L.;Lee, James A.;Kripfgans, Oliver D.;Carson, Paul L.;Fowlkes, J. Brian
通讯作者：
Fowlkes, J. Brian
DOI：
10.1109/tuffc.2002.1009331
发表时间：
2002-06-01
影响因子：
3.6
作者：
Kripfgans, OD;Fowlkes, JB;Carson, PL
通讯作者：
Carson, PL
影响因子：
9.7
作者：
Abdalkader, Rodi;Kawakami, Shigeru;Hashida, Mitsuru
通讯作者：
Hashida, Mitsuru