Ho Yi-Ju, Yeh Chih-Kuang
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
Theranostics. 2017 Apr 3;7(6):1477-1488. doi: 10.7150/thno.19099. eCollection 2017.
Solid tumors with poorly perfused regions reveal some of the treatment limitations that restrict drug delivery and therapeutic efficacy. Acoustic droplet vaporization (ADV) has been applied to directly disrupt vessels and release nanodroplets, ADV-generated bubbles (ADV-Bs), and drugs into tumor tissue. In this study, we investigated the behavior of ADV-Bs stimulated by US, and evaluated the possibility of moving intertissue ADV-Bs into the poorly perfused regions of solid tumors. Intravital imaging revealed intertissue ADV-B formation, movement, and cavitation triggered by US, where the distance of intertissue ADV-B movement was 33-99 µm per pulse. When ADV-Bs were applied to tumor cells, the cell membrane was damaged, increasing cellular permeability or inducing cell death. The poorly perfused regions within solid tumors show enhancement due to ADV-B accumulation after application of US-triggered ADV-B. The intratumoral nanodroplet or ADV-B distribution around the poorly perfused regions with tumor necrosis or hypoxia were demonstrated by histological assessment. ADV-B formation, movement and cavitation could induce cell membrane damage by mechanical force providing a mechanism to overcome treatment limitations in poorly perfused regions of tumors.
存在灌注不良区域的实体瘤显示出一些限制药物递送和治疗效果的治疗局限性。声滴汽化（ADV）已被用于直接破坏血管并将纳米液滴、ADV产生的气泡（ADV-Bs）和药物释放到肿瘤组织中。在本研究中，我们研究了超声刺激下ADV-Bs的行为，并评估了将组织间ADV-Bs移动到实体瘤灌注不良区域的可能性。活体成像显示了超声触发的组织间ADV-B的形成、移动和空化，其中每个脉冲组织间ADV-B的移动距离为33-99μm。当将ADV-Bs应用于肿瘤细胞时，细胞膜受损，细胞通透性增加或诱导细胞死亡。在应用超声触发的ADV-B后，由于ADV-B的积累，实体瘤内灌注不良区域显示出增强。通过组织学评估证实了肿瘤坏死或缺氧的灌注不良区域周围的瘤内纳米液滴或ADV-B分布。ADV-B的形成、移动和空化可通过机械力诱导细胞膜损伤，为克服肿瘤灌注不良区域的治疗局限性提供了一种机制。
