Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
Ultrason Sonochem. 2023 Mar;94:106342. doi: 10.1016/j.ultsonch.2023.106342. Epub 2023 Feb 23.
Sonodynamic therapy involving the non-invasive and local generation of lethal reactive oxygen species (ROS) via ultrasound (US) with sonosensitizers has been proposed as an emerging tumor therapy strategy. However, such therapy is usually associated with inertial cavitation and unnecessary damage to healthy tissue because current sonosensitizers have insufficient sensitivity to US. Here, we report the use of a new proposed sonosensitizer, carbon dots (C-dots), to assemble microbubbles with a gas core (C-dots MBs). As the C-dots were directly integrated into the MB shell, they could effectively absorb the energy of inertial cavitation and transfer it to ROS. Our results revealed the appearance of O, •OH, and HO after US irradiation of C-dots MBs. In in vitro experiments, treatment with C-dots MBs plus US induced lipid peroxidation, elevation of intracellular ROS, and apoptosis in 32.5%, 45.3%, and 50.1% of cells respectively. In an animal solid tumor model, treatment with C-dots MBs plus US resulted in a 3-fold and 2.5-fold increase in the proportion of ROS-damaged cells and apoptotic cells, respectively, compared to C-dots MBs alone. These results will pave the way for the design of novel multifunctional sonosensitizers for SDT tumor therapy.
声动力学疗法通过超声（US）与声敏剂非侵入性和局部产生致命的活性氧（ROS），已被提议作为一种新兴的肿瘤治疗策略。然而，这种治疗通常与惯性空化和对健康组织的不必要损伤有关，因为目前的声敏剂对 US 的敏感性不足。在这里，我们报告使用一种新提出的声敏剂，即碳点（C-dots），与具有气体核心的微泡（C-dots MBs）组装。由于 C-dots 直接集成到 MB 壳中，它们可以有效地吸收惯性空化的能量并将其转化为 ROS。我们的结果显示，在 C-dots MBs 的 US 照射后出现了 O，•OH 和 HO。在体外实验中，用 C-dots MBs 加 US 处理分别诱导了 32.5%、45.3%和 50.1%的细胞发生脂质过氧化、细胞内 ROS 升高和细胞凋亡。在动物实体瘤模型中，与单独使用 C-dots MBs 相比，用 C-dots MBs 加 US 处理导致 ROS 损伤细胞和凋亡细胞的比例分别增加了 3 倍和 2.5 倍。这些结果将为设计用于 SDT 肿瘤治疗的新型多功能声敏剂铺平道路。
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