Wu Songsong, Zhang Dongyun, Yu Jie, Dou Jianping, Li Xin, Mu Mengjuan, Liang Ping
Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China.
Department of Ultrasonography, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Front Pharmacol. 2020 Feb 26;11:85. doi: 10.3389/fphar.2020.00085. eCollection 2020.
Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer, and the 5-year overall survival (OS) rate for HCC remains unsatisfying worldwide. Microwave ablation (MWA) is a minimally invasive therapy that has made progress in treating HCC. However, HCC recurrence remains problematic. Therefore, combination therapy may offer better outcomes and enhance MWA efficiency through improved tumor control. We have developed doxorubicin-loaded liposomes (DNPs) as an efficient nanoplatform to enhance MWA of hepatocellular carcinoma even at the mild ablation condition. In this study, we demonstrated that the uptake of DNPs by HCC cells was increased 1.5-fold compared with that of free DOX. Enhanced synergism was observed in the combination of DNPs and MWA, which induced nearly 80% cell death. The combination of mild MWA and DNPs enhanced the ablation efficiency of HCC with significant inhibition of liver tumors and accounted for the longest survival rate among all groups. A much higher accumulation of the DNPs was observed in the transitional zone than in the ablation zone. No apparent systemic toxicity was observed for any of the treatments after 14 days. The present work demonstrates that DNPs combined with MWA could be a promising nanoparticle-based therapeutic approach for the treatment of hepatocellular carcinoma and shows potential for future clinical applications.
肝细胞癌（HCC）是癌症死亡的第三大主要原因，全球范围内HCC的5年总生存率仍不尽人意。微波消融（MWA）是一种微创治疗方法，在治疗HCC方面取得了进展。然而，HCC复发仍然是个问题。因此，联合治疗可能会带来更好的效果，并通过改善肿瘤控制提高MWA的效率。我们已经开发了载有阿霉素的脂质体（DNPs）作为一种高效的纳米平台，即使在轻度消融条件下也能增强肝细胞癌的MWA效果。在本研究中，我们证明HCC细胞对DNPs的摄取量比游离阿霉素增加了1.5倍。观察到DNPs与MWA联合使用时具有增强的协同作用，可诱导近80%的细胞死亡。轻度MWA与DNPs联合使用提高了HCC的消融效率，显著抑制了肝肿瘤，并在所有组中导致最长的生存率。在过渡区观察到DNPs的积累比消融区高得多。14天后，任何治疗均未观察到明显的全身毒性。目前的研究表明，DNPs与MWA联合使用可能是一种有前途的基于纳米颗粒的肝细胞癌治疗方法，并显示出未来临床应用的潜力。
