肝癌射频消融（RFA）术后复发与转移导致患者预后差，肿瘤残余且亚致死热激上调残癌细胞干性和上皮间质转化（EMT）是重要原因。三氧化二砷（ATO）可同时抑制干性和EMT，但毒性大，且RFA后局部组织药物渗透难度增加。因此，寻求一种低毒性、高渗透给药方式是应用ATO治疗残癌的关键。中性粒细胞（NE）可作为高渗透靶向急性炎症组织的新型药物载体。基于此，我们前期将NE与载ATO和全氟戊烷（PFP）脂质体孵育后获得活细胞递药体系NE-LAP，载药后NE保持良好活性。本项目拟：①进一步优化NE-LAP，在细胞及动物实验探讨其炎症趋化靶向残癌输药的作用；②探讨通过聚焦超声触发PFP相变爆破NE，实现其超声可视化释放药物的性能；③评估NE-LAP低毒高效杀伤残癌细胞、抑制肝癌RFA术后复发与转移的作用。本项目有望开发一种NE驱动的新型活细胞递药体系，并实现其超声可视化药物控释，为治疗RFA残癌提供新思路。

Recurrence and metastasis of hepatocellular carcinoma after radiofrequency ablation (RFA) leads to poor prognosis. This is mainly caused by residual cancer and its upregulation of stemness and epithelial mesenchymal transition (EMT) by sub-lethal heat during RFA. Arsenic trioxide (ATO) can inhibit both stemness and EMT. However, its clinical application is limited due to its high toxicity and the difficulty of drug penetration caused by RFA. Therefore, it is crucial to develop a method with low toxicity and high penetration to deliver ATO. Neutrophil (NE) can be served as a novel drug carrier with high penetration and targeting acute inflammatory tissues. Based on this, we have obtained a cell-based drug delivery system, NE-LAP, by incubating NE with liposomes, which were originally loaded with ATO and perfluoropentane (PFP). And we found NE-LAP exhibit good inflammation chemotaxis. Hence, this project is aimed to optimize NE-LAP as well as explore its role of targeting residual cancer by inflammatory chemotaxis both in vitro and in vivo. Subsequently, exploring the feasibility of blasting NE to release ATO with ultrasonic visualization by using a short-pulsed focused ultrasound sonication to trigger PFP vaporization. Last but not least, we intend to evaluate the effect of NE-LAP on suppressing residual cancer and inhibiting the recurrence and metastasis of hepatocellular carcinoma after RFA with low toxicity and high efficiency. This project is expected to develop a new cell-based drug delivery system, as well as realize its role of controlled drug release with ultrasonic visualization. This work would bring new ideas for the treatment of residual cancer after RFA.