Nanomedicine-Mediated Nanosecond Pulsed Electric Field Ablation for Enhanced Cancer Treatment: The Case of Anti-HCC
Xinzhu Yang1, Qiong Wu1 Xiaoxiong Zhao1, Yujun Song1, Danjing Guo2, Liangjie Hong2, Xinhua Chen2; 1Center for Modern Physics Technology, School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China; 2Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310003, China.
Abstract
A novel combined anti-tumor therapy was developed by nanomedicines (i.e., Au@CoFeB-Rg3 NMs) mediated nanosecond pulsed electric field (nsPEF) ablation, showing a significant synergistic anti-cancer therapeutical effect using hepatocellular carcinoma (HCC) as the pathological model. The in vitro cytotoxicity study of the combined therapy suggests that administration of NMs into the cell culture media in 4 hours after nsPEF treatment exhibits a much better anti-HCC effect than administration of NMs after 4 hours by nsPEF, much better than treated solely by NMs or nsPEF. The optimal anti-HCC effect can be achieved by immediate administration of NMs after nsPEF treatment with at least 60 pulse repeats. The vivo experiments of the combined therapy also demonstrate a substantially improved therapeutic effect anti-HCC when compared to using only NMs or nsPEF ablation. Furthermore, the combined therapy effectively inhibits tumor cell metastasis during the nsPEF ablation process and reduces recurrence in the post-operative stage, as evidenced by blood chemokine analysis and stained pathological section observation. Importantly, organ functions (e.g., liver, kidney, and heart) in tumor-bearing mice are notably ameliorated by the combined therapy compared to both control experiments and treatments involving standalone nsPEF or NMs. Further analysis of the therapeutic mechanism suggests that the significantly enhanced anti-HCC efficacy arise from the synergistic interplay between in situ electric shock and polarization of nsPEF, augmented cell internalization of NMs after the electroporation by nsPEF, the anti-tumor abscopal immune effect, and the complementary amelioration on organ dysfunction caused by tumor-bearing through NMs and nsPEF.
Speaker
Yujun Song
University of Science and Technology Beijing
中国
Discussion
Ask question
