Oral Microalgae‐Based Biosystem to Enhance Irreversible Electroporation Immunotherapy in Hepatocellular Carcinoma

Abstract Irreversible electroporation (IRE) is a novel local tumor ablation technique that can potentially stimulate immune responses. However, IRE alone cannot effectively activate the immune system or prevent distant metastases. Therefore, this study utilized the biocompatibility of Chlorella vulgaris ( C. vulgaris ) and polydopamine (PDA) adhesive properties to encapsulate a PD‐1 inhibitor (PI). The PDA coating protects the drug from degradation by stomach acid and enhances its intestinal absorption. This carrier demonstrates excellent in vivo drug release control and biodistribution, significantly increasing the oral bioavailability of PI. Combining IRE with this natural carrier significantly improves the therapeutic efficacy, which increases the local drug concentration and activates the immune system. This system demonstrates significantly improved therapeutic efficacy against local tumors compared with PI or IRE alone and significantly reduces PI‐associated side effects. A convenient oral delivery system is developed using this readily available natural micro‐carrier that not only improves the therapeutic effect of IRE but also mitigates its adverse effects, indicating significant potential for clinical applications. This discovery offers a new strategy for hepatocellular carcinoma treatment with the potential to improve patient outcomes.