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

Area of Science:

• Biomedical Engineering
• Oncology
• Plasma Medicine

Background:

• Hepatocellular carcinoma (HCC) poses a global health challenge, with existing therapies like transarterial chemoembolization (TACE) exhibiting limitations in tumor specificity, metastasis promotion, and inflammation.
• Cold atmospheric plasma (CAP) shows promise for tumor-selective ablation but is hindered by insufficient tissue penetration depth.

Purpose of the Study:

• To develop and evaluate the FlexiPlasma microcatheter (FPM) for precise delivery of optimized CAP to deep-seated tumors, overcoming penetration limitations.
• To investigate the mechanism of CAP-induced tumor cell death and its immunomodulatory effects in the context of HCC treatment.

Main Methods:

• Development of the FlexiPlasma microcatheter (FPM) with integrated flexible microtubes and ring electrodes for controlled CAP delivery.
• Optimization of FPM-generated CAP to eliminate cytotoxic byproducts (UV, ozone) and induce Gasdermin-C (GSDMC)-mediated pyroptosis.
• Combination of FPM with an embolic material (EM), PPP@CD hydrogel, to enhance delivery, embolization, and drug release characteristics.

Main Results:

• Optimized FPM-generated CAP selectively induces pyroptosis in HCC cells via a ROS/Caspase-8/GSDMC pathway, leveraging high GSDMD expression in tumors and absence in normal tissues.
• The FPM-EM combination demonstrated effective tumor embolization, sustained release of therapeutic agents, and potentiation of antitumor immunity, including CD4+ and CD8+ T-cell responses.
• The FPM-EM strategy proved safe and effective, showing minimal inflammation compared to conventional therapies.

Conclusions:

• The FPM-EM system represents a safe, effective, and minimally invasive therapeutic approach for HCC, offering a non-inflammatory pyroptosis mechanism.
• This innovative platform broadens the application of CAP-based cancer therapies and holds potential for treating other tumors and incorporating diverse therapeutic agents.