探讨加载裂解的 OK-432 (lyOK-432) 和阿霉素 (DOX) 的可注射水凝胶对肝细胞癌 (HCC) 不完全射频消融 (iRFA) 后残留肝癌的疗效，并探讨其潜在机制。比较了 OK-432 和 lyOK-432 在激活树突状细胞 (DC) 方面的作用。将 RADA16-I (R) 肽溶解在 lyOK-432 (O) 和 DOX (D) 的混合物中以形成 ROD 水凝胶。评估了ROD水凝胶的特性。在不同的治疗后测量肿瘤反应和小鼠存活率。测量免疫细胞数量和细胞因子水平，并在体外和体内评估 DC 中 cGAS/STING/IFN-I 信号通路的激活情况。LyOK-432 在促进 DC 成熟和促进 DC 成熟方面比 OK-432 更有效。激活 IFN-I 途径。 ROD是一种可注射水凝胶，可有效负载lyOK-432和DOX，并具有控释特性。与其他疗法相比，ROD 治疗实现了最高的肿瘤坏死率 (p<0.001) 和最长的生存时间 (p<0.001)。 ROD组还表现出最高的DC、CD4 T细胞和CD8 T细胞百分比(p < 0.001)，最低水平的Treg细胞(p < 0.001)，以及最高的IFN-γ和TNF-α表达水平(p < 0.001)。 p < 0.001）与其他组相比。 lyOK-432联合DOX治疗后DC中pSTING、pIRF3和IFN-β的表达水平明显高于其他治疗。 ROD组中存活的小鼠表现出对皮下肿瘤再次攻击的生长抑制。新型ROD肽水凝胶通过激活STING通路诱导抗肿瘤免疫，这对HCC iRFA后残留肝癌的治疗有效。© 2023。作者（ s）。

To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC), and explore the underlying mechanism.The effect of OK-432 and lyOK-432 was compared in activating dendritic cells (DCs). RADA16-I (R) peptide was dissolved in a mixture of lyOK-432 (O) and DOX (D) to develop an ROD hydrogel. The characteristics of ROD hydrogel were evaluated. Tumor response and mice survival were measured after different treatments. The number of immune cells and cytokine levels were measured, and the activation of cGAS/STING/IFN-I signaling pathway in DC was evaluated both in vitro and in vivo.LyOK-432 was more effective than OK-432 in promoting DC maturation and activating the IFN-I pathway. ROD was an injectable hydrogel for effectively loading lyOK-432 and DOX, and presented the controlled-release property. ROD treatment achieved the highest tumor necrosis rate (p < 0.001) and the longest survival time (p < 0.001) compared with the other therapies. The ROD group also displayed the highest percentages of DCs, CD4+ T cells and CD8+ T cells (p < 0.001), the lowest level of Treg cells (p < 0.001), and the highest expression levels of IFN-γ and TNF-α (p < 0.001) compared with the other groups. The expression levels of pSTING, pIRF3, and IFN-β in DCs were obviously higher after treatment of lyOK-432 in combination with DOX than the other therapies. The surviving mice in the ROD group showed a growth inhibition of rechallenged subcutaneous tumor.The novel ROD peptide hydrogel induced an antitumor immunity by activating the STING pathway, which was effective for treating residual liver cancer after iRFA of HCC.© 2023. The Author(s).