Smartly Assembled near-Micron RF-Responsive Agents Bridge Transarterial Embolization and Immunothermal Potentiation.

Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to the limited efficacy of conventional treatments like surgery, radiofrequency ablation (RFA), and transarterial embolization (TAE). Here, we develop an innovative TAE and immunothermal therapy strategy based on smartly assembled near-micron layered double hydroxide particles co-loaded with STING agonist (NM-LDHs-cGP). By smartly responding to local charge fluctuations and microenvironmental changes, NM-LDHs undergo self-assembly and hierarchical stacking to form stable vascular embolic agents, thereby achieving superior embolization efficacy and excellent responsiveness to radiofrequency-induced thermal stimulation. NM-LDHs-cGP activates the cGAS-STING pathway, promotes dendritic cell maturation, and elicits robust CD8 T and NK cell responses. Translational studies using human HCC tissues and immune cells confirm its ability to enhance RFA-induced cytotoxicity and trigger potent innate and adaptive immune activation. These findings establish smartly assembled NM-LDHs-cGP as a promising paradigm for combinatorial embolization-thermal ablation-immunotherapy in liver cancer.