Cao Jing, Wang Ling, Li Jiarui, Song Mengyu, Zheng Yinuo, He Xiangling, Li Xiaoying, Xu Songcheng, Sun Litao
Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China; Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
Ultrason Sonochem. 2025 Apr;115:107296. doi: 10.1016/j.ultsonch.2025.107296. Epub 2025 Mar 1.
Histotripsy is a cavitation-based tumor ablation technology. To achieve precise cavitation-based ablation requires investigating the cavitation behavior of the bubble cloud and their impact on tumor tissue. This study explored the cavitation behavior of bubble clouds generated by perfluoropentane (PFP)-loaded nanodroplets and efficacy of bubble cloud cavitation in tumor ablation under varying ultrasound intensities. PFP-loaded nanodroplets (∼200 nm) were employed as exogenous cavitation nuclei to reducing the required ultrasound energy for activation of bubble cloud. We investigated the formation, vibration, and collapse of bubble clouds in solution and phantom models under varying ultrasound intensities. Results indicated distinct cavitation patterns: (1) Nanodroplets slowly vaporized and formed continuously vibrating bubble clouds; (2) Nanodroplets rapidly vaporized and resulted in quickly collapsing bubble clouds. At both the cellular and animal levels, cavitation ablation efficacy was examined, revealing that all bubble cloud cavitation patterns could induce immunogenic cell death (ICD), promoting the release of damage-associated molecular patterns (DAMPs) and triggering effector immune cell deployment of peripheral immune response and local tumor infiltration. During the treatment, the ultrasound intensity of 0.5 W/cm had the highest level of central tumor CD8 T cell infiltration. The conclusion was that sustained bubble cloud oscillation, rather than rapid vaporization and rupture, proved more beneficial for antitumor therapy, particularly in enhancing the local infiltration of effector immune cells.
组织粉碎术是一种基于空化作用的肿瘤消融技术。要实现精确的基于空化作用的消融，需要研究气泡云的空化行为及其对肿瘤组织的影响。本研究探讨了载有全氟戊烷（PFP）的纳米液滴产生的气泡云的空化行为，以及在不同超声强度下气泡云空化在肿瘤消融中的效果。载有PFP的纳米液滴（约200纳米）被用作外源性空化核，以降低激活气泡云所需的超声能量。我们研究了在不同超声强度下溶液和体模模型中气泡云的形成、振动和坍塌。结果表明存在明显的空化模式：（1）纳米液滴缓慢汽化并形成持续振动的气泡云；（2）纳米液滴迅速汽化并导致快速坍塌的气泡云。在细胞和动物水平上，均对空化消融效果进行了检测，结果显示所有气泡云空化模式均可诱导免疫原性细胞死亡（ICD），促进损伤相关分子模式（DAMPs）的释放，并触发外周免疫反应的效应免疫细胞部署和局部肿瘤浸润。在治疗过程中，0.5W/cm的超声强度使中央肿瘤CD8 T细胞浸润水平最高。结论是，持续的气泡云振荡，而非快速汽化和破裂，对抗肿瘤治疗更为有益，尤其是在增强效应免疫细胞的局部浸润方面。
