FlexiPlasma Microcatheter-Embolic Material (FPM-EM) Platform: A Non-Inflammatory Pyroptosis Strategy for Precision Hepatocellular Carcinoma Therapy.

Abstract

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.