Thermal ablation (TA) as an effective method treating hepatocellular carcinoma (HCC) in clinics is facing great challenges of high recurrence and metastasis. Although immune-checkpoint blockade (ICB)-based immunotherapy has shown potential to inhibit recurrence and metastasis, the combination strategy of ICB and thermal ablation has shown little progress in HCC treatments. The tremendous hurdle for combining ICB with thermal ablation lies with the insufficient antigen internalization and immaturity of tumor-infiltrating dendritic cells (TIDCs) which leads to an inferior immune response to distant tumor growth and metastasis. Herein, an antigen-capturing nanoplatform, whose surface was modified with mannose as a targeting ligand, was constructed for co-delivering tumor-associated antigens (TAAs) and m6A demethylases inhibitor (i.e., fat mass and obesity associated gene (FTO) inhibitor) into TIDCs. In vivo results demonstrate that the intratumoral injection of nanodrug followed by HCC thermal ablation promotes dendritic cells (DCs) maturation, improves tumor infiltration of effector T cells and generates immune memory, which synergize with ICB treatment to inhibit the distant tumor growth and lung metastasis. Therefore, the antigen-capturing and FTO-inhibiting nanodrug holds potential to boost the ICB-based immunotherapy against HCC after thermal ablation.

热消融（TA）作为临床治疗肝细胞癌（HCC）的有效方法，面临着高复发和高转移的巨大挑战。尽管基于免疫检查点阻断 (ICB) 的免疫疗法已显示出抑制复发和转移的潜力，但 ICB 和热消融的组合策略在 HCC 治疗中几乎没有进展。将 ICB 与热消融相结合的巨大障碍在于抗原内化不足和肿瘤浸润树突状细胞 (TIDC) 的不成熟，导致对远处肿瘤生长和转移的免疫反应较差。在此，构建了一种表面用甘露糖作为靶向配体修饰的抗原捕获纳米平台，用于共同递送肿瘤相关抗原（TAA）和m6A去甲基化酶抑制剂。即，脂肪量和肥胖相关基因 (FTO) 抑制剂）进入 TIDC。体内结果表明，肿瘤内注射纳米药物，然后进行 HCC 热消融可促进树突状细胞 (DC) 成熟，改善效应 T 细胞的肿瘤浸润并产生免疫记忆，与 ICB 治疗协同抑制远处肿瘤生长和肺转移。因此，抗原捕获和抑制 FTO 的纳米药物具有促进热消融后基于 ICB 的 HCC 免疫疗法的潜力。