肝转移是治疗侵袭性癌症的一个重要障碍，当前的治疗选项常常不够。为了克服这些挑战，人们对利用脂质包膜微气泡（MBs）和纳米气泡（NBs）进行超声介导药物输送的兴趣日益增长，这被认为是增强药物输送到肿瘤的有希望的策略。我们先前的研究在体外使用低频超声研究表明注射多柔比星负载C 3 F 8 纳米气泡（hDox-NB，280 ± 123 nm）改善了癌症治疗的潜力。在本研究中，我们考察了超声刺激患有原位大鼠肝肿瘤的hDox-NB药代动力学和生物分布。我们将其与体积相同的微气泡（hDox-MB，1104 ± 373 nm）的输送和治疗效果进行了比较。结果显示，在hDox-MB+TUS和hDox-NB+TUS处理的肿瘤中，hDox聚集相似。然而，在hDox-NB+TUS处理下，肿瘤中的细胞凋亡明显增加，而正常肝脏中的非靶向细胞凋亡减少。与hDox-MB+TUS相比，hDox-NB+TUS处理后，肿瘤与肝脏的细胞凋亡比例提高了9.4倍，这表明在使用hDox-NB+TUS时，治疗效果和特异性显著增加。这些发现强调了这种方法作为肝肿瘤可行治疗方式的潜力。通过阐明体内药物载体气泡的行为，我们旨在为开发更有效的肝癌治疗方法做出贡献，从而最终改善患者预后并减少非靶向的副作用。

Liver metastasis is a major obstacle in treating aggressive cancers, and current therapeutic options often prove insufficient. To overcome these challenges, there has been growing interest in ultrasound-mediated drug delivery using lipid-shelled microbubbles (MBs) and nanobubbles (NBs) as promising strategies for enhancing drug delivery to tumors. Our previous work demonstrated the potential of Doxorubicin-loaded C 3 F 8 NBs (hDox-NB, 280 ± 123 nm) in improving cancer treatment in vitro using low-frequency ultrasound. In this study, we investigated the pharmacokinetics and biodistribution of sonicated hDox-NBs in orthotopic rat liver tumors. We compared their delivery and therapeutic efficiency with size-isolated MBs (hDox-MB, 1104 ± 373 nm). Results showed a similar accumulation of hDox in tumors treated with hDox-MBs and unfocused therapeutic ultrasound (hDox-MB+TUS) and hDox-NB+TUS. However, significantly increased apoptotic cell death in the tumor and fewer off-target apoptotic cells in the normal liver were found upon the treatment with hDox-NB+TUS. The tumor-to-liver apoptotic ratio was elevated 9.4-fold following treatment with hDox-NB+TUS compared to hDox-MB+TUS, suggesting that the therapeutic efficacy and specificity are significantly increased when using hDox-NB+TUS. These findings highlight the potential of this approach as a viable treatment modality for liver tumors. By elucidating the behavior of drug-loaded bubbles in vivo , we aim to contribute to developing more effective liver cancer treatments that could ultimately improve patient outcomes and decrease off-target side effects.