Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China.
J Biomed Mater Res B Appl Biomater. 2021 Nov;109(11):1796-1806. doi: 10.1002/jbm.b.34839. Epub 2021 Apr 10.
Sonodynamic therapy (SDT) is an emerging noninvasive therapeutic approach, which could penetrate deep-seated tissues and activate sonosensitizer to produce cytotoxic reactive oxygen species (ROS). Nevertheless, the hypoxic tumor microenvironment significantly limits the efficiency of SDT due to its oxygen-consumption treatment principle. To break hypoxia-induced resistance and improve the efficacy of SDT, we developed shell-core structured oxygen-sufficient nanobubbles(NBs), which were designed with a lipid shell loaded the sonosensitizer IR780 and a gas core loaded with oxygen. With the aid of ultrasound-targeted microbubble destruction (UTMD), IR780@O NBs not only make sonosensitizers more effectively enriched at the tumor site in a controlled manner, but also directly mediate oxygen release and provide sufficient oxygen for producing more ROS to induce cell apoptosis. Thus, IR780@O NBs can efficiently inhibit the proliferation of Hep-G2 cells under ultrasound exposure. What is more, IR780@O NBs have a potential for contrast enhanced ultrasound (CEUS) imaging. We believe that our oxygen-sufficient NBs trigged by UTMD could be an ideal therapeutic and imaging system for hepatocellular carcinoma.
声动力学疗法（SDT）是一种新兴的无创治疗方法，它可以穿透深部组织并激活声敏剂产生细胞毒性活性氧（ROS）。然而，由于其耗氧治疗原理，缺氧肿瘤微环境显著限制了 SDT 的效率。为了打破缺氧诱导的耐药性并提高 SDT 的疗效，我们开发了壳核结构的富氧纳米气泡（NBs），其设计为负载声敏剂 IR780 的脂质壳和负载氧气的气体核。在超声靶向微泡破坏（UTMD）的辅助下，IR780@O NBs 不仅可以更有效地控制地将声敏剂更有效地富集在肿瘤部位，而且还可以直接介导氧气释放并为产生更多 ROS 以诱导细胞凋亡提供足够的氧气。因此，IR780@O NBs 可以在超声暴露下有效地抑制 Hep-G2 细胞的增殖。更重要的是，IR780@O NBs 具有对比增强超声（CEUS）成像的潜力。我们相信，我们通过 UTMD 触发的富氧 NBs 可以成为治疗肝癌的理想治疗和成像系统。
