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.