Li Changhong, Cheng Hongwei, Zhuang Ziqi, Cao Fei, Liu Hui, Zhao Liqian, Rizvi Syed Faheem Askari, Wang Kanqi, Yang Liuyin, Lu Xiaowei, Zheng Yating, Zhang Yu, He Pan, Mao Jingsong, Wen Xiaofei, Zhang Liang, Jiang Lili, Lin Jinyong, Li Dong, Chu Chengchao, Zeng Yun, Lu Zhixiang, Liu Chao, Thompson Erik W, Chen Zhitong, Wang Peiyu, Liu Gang
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, Fujian Engineering Research Center of Molecular Theranostic Technology, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
Small Methods. 2025 Aug;9(8):e2500231. doi: 10.1002/smtd.202500231. Epub 2025 Apr 25.
Hepatocellular carcinoma (HCC) remains a global challenge, with conventional locoregional therapies like transarterial chemoembolization (TACE) lacking tumor specificity and promoting metastasis and inflammation. Cold atmospheric plasma (CAP) offers a tumor-selective ablation strategy but suffers from limited tissue penetration. To overcome this, the FlexiPlasma microcatheter (FPM) is developed, integrating flexible non-metallic microtubes and ring-shaped electrodes for precise CAP delivery to deep tumors. The optimized FPM-generated CAP eliminates cytotoxic UV and ozone while inducing tumor-specific pyroptosis via a ROS/Caspase-8/GSDMC pathway. Gasdermin-C (GSDMC) is highly expressed in liver tumors but absent in normal tissues, ensuring selective targeting with minimal inflammation. FPM is combined with embolic material (EM), PPP@CD hydrogel, enhancing injectability, tumor embolization, and sustained drug release. This FPM-EM strategy potentiates antitumor immunity, particularly CD4+ and CD8+ T-cell responses. These findings establish FPM-EM as a safe, effective, and minimally invasive therapy for HCC, revealing a non-inflammatory pyroptosis mechanism and broadening the potential of CAP-based cancer treatments. The FPM-EM combination offers promising new therapeutic options for HCC, addressing the limitations of TACE. Furthermore, the FPM-EM platform can be extended to the interventional therapy of other tumors and adapted to incorporate various drugs and nano-/micro-materials, highlighting the strong potential for future clinical translation.
肝细胞癌（HCC）仍然是一项全球性挑战，诸如经动脉化疗栓塞术（TACE）等传统局部区域疗法缺乏肿瘤特异性，会促进转移和炎症。冷大气等离子体（CAP）提供了一种肿瘤选择性消融策略，但组织穿透性有限。为克服这一问题，研发了FlexiPlasma微导管（FPM），它集成了柔性非金属微管和环形电极，用于将CAP精确递送至深部肿瘤。优化后的FPM产生的CAP消除了具有细胞毒性的紫外线和臭氧，同时通过ROS/Caspase-8/GSDMC途径诱导肿瘤特异性焦亡。Gasdermin-C（GSDMC）在肝肿瘤中高表达，但在正常组织中不存在，确保了选择性靶向且炎症最小。FPM与栓塞材料（EM）、PPP@CD水凝胶相结合，增强了可注射性、肿瘤栓塞和药物持续释放。这种FPM-EM策略增强了抗肿瘤免疫力，尤其是CD4+和CD8+ T细胞反应。这些发现确立了FPM-EM作为一种安全、有效且微创的HCC治疗方法，揭示了一种非炎症性焦亡机制，并拓宽了基于CAP的癌症治疗潜力。FPM-EM组合为HCC提供了有前景的新治疗选择，解决了TACE的局限性。此外，FPM-EM平台可扩展至其他肿瘤的介入治疗，并可适应纳入各种药物和纳米/微米材料，凸显了未来临床转化的强大潜力。
