Enhanced magnetic thermal ablation combined with immunotherapy for hepatocellular carcinoma using engineering microspheres

Hepatocellular carcinoma (HCC) remains a formidable challenge in oncology, characterized by high metastatic potential and recurrence rates. Traditional microwave ablation technique faces limitations due to operator dependency and potential complications. To address these challenges, we developed micron-sized polyacrylamide-iron carbonyl magnetic hyperthermia microspheres (PAM@Fe(CO)₅ MSs) for non-invasive magnetic thermal ablation (MTA). These microspheres, synthesized via the SPG membrane emulsification technique, exhibit commendable biocompatibility, size stability, and robust magnetic thermal effects. When combined with PD-1 monoclonal antibody immunotherapy, PAM@Fe(CO)₅ MSs demonstrated significant synergistic effects, leading to the markedly curtailed growth of metastatic tumors in mouse models. Further, in a rabbit orthotopic liver tumor model, MTA using PAM@Fe(CO)₅ MSs showcased excellent safety and efficacy, with minimal impact on liver function and no observable toxicity in critical organs. This innovative approach not only enhances anti-tumor efficacy by activating the host's T-cell immune response but also overcomes the immune-suppressive tumor microenvironment. Our findings suggest that combining MTA with immunotherapy may offer a viable treatment approach for HCC and possibly other solid tumors, paving the way for safer and more effective clinical applications.