Noninvasive Ablation of Prostate Cancer Spheroids Using Acoustically-Activated Nanodroplets
Noninvasive Ablation of Prostate Cancer Spheroids Using Acoustically-Activated Nanodroplets
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DOI：
10.1021/acs.molpharmaceut.6b00617
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发表时间：
2016-12-01
影响因子：
4.9
通讯作者：
ElSayed, Mohamed E. H.
中科院分区：
文献类型：
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作者：
Aydin, Omer;Vlaisavljevich, Eli;ElSayed, Mohamed E. H.
我们使用两亲性三嵌段共聚物开发了声激活纳米液滴（nd），该共聚物可自组装并封装不同的全氟碳化合物，包括全氟戊烷（PFP）和全氟己烷（PFH）。与单独进行组化处理观察到的空化压力相比，将组化脉冲（即短、高压、超声脉冲）应用于PFP-和PFH-NDs溶液，在显著降低的声压下产生气泡云。在本报告中，我们总结了低频（345和500 kHz）组织切片法结合PFP-NDs和PFH-NDs对前列腺癌PC-3和C4-2B细胞消融的结果。使用定制的组织学换能器与显微镜和高速记录相机相结合，我们在溶液和组织模拟凝胶幻象中对不同超声机制的响应进行了空化气泡云的生成成像。我们量化了单个癌细胞和悬浮在溶液中并包埋在组织幻影中的三维球体的相关消融，以比较PFP-NDs和PFH-NDs的消融能力。结果显示，在高声压（26.2 MPa）下，组织切片脉冲消融了80%嵌入在模拟组织凝胶幻象中的前列腺癌球体。相比之下，将极低声压（12.8 MPa）下的组织切片脉冲与PFP-NDs和PFH-NDs相结合，分别可使肿瘤球体体积的40%和80%消融。这些结果显示了声激活纳米粒子作为一种图像引导的实体肿瘤消融治疗的潜力，并强调了PFH-纳米粒子更高的消融能力，这与被封装的PFH的沸点和形成的泡云的稳定性有关。
We have developed acoustically activated nanodroplets (NDs) using an amphiphilic triblock copolymer, which self-assembles and encapsulates different perfluorocarbons including perfluoropentane (PFP) and perfluorohexane (PFH). Applying histotripsy pulses (i.e., short, high pressure, ultrasound pulses) to solutions of PFP- and PFH-NDs generated bubble clouds at a significantly reduced acoustic pressure compared to the cavitation pressure observed for histotripsy treatment alone. In this report, we summarize the results of combining histotripsy at low frequency (345 and 500 kHz) with PFP-NDs and PFH-NDs on the ablation of PC-3 and C4-2B prostate cancer cells. Using custom built histotripsy transducers coupled to a microscope and a high speed recording camera, we imaged the generation of a cavitation bubble cloud in response to different ultrasound regimes in solution and in tissue-mimicking gel phantoms. We quantified the associated ablation of individual cancer cells and 3D spheroids suspended in solution and embedded in tissue phantoms to compare the ablative capacity of PFP-NDs and PFH-NDs. Results show that histotripsy pulses at high acoustic pressure (26.2 MPa) ablated 80% of prostate cancer spheroids embedded in tissue-mimicking gel phantoms. In comparison, combining histotripsy pulses at a dramatically lower acoustic pressure (12.8 MPa) with PFP-NDs and PFH-NDs caused an ablation of 40% and 80% of the tumor spheroid volumes, respectively. These results show the potential of acoustically activated NDs as an image-guided ablative therapy for solid tumors and highlight the higher ablative capacity of PFH-NDs, which correlates with the boiling point of the encapsulated PFH and the stability of the formed bubble cloud.