Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway is an essential DNA-sensing pathway to regulate the innate and adaptive immune response, which plays an important role in tumor immunotherapy. Although the STING agonists can be used, they are limited by their inability to target immune cells and systemic immunotoxicity, calling for novel strategies to accurately and effectively activate the cGAS-STING signaling pathway. Herein, mannose-modified stearic acid-grafted chitosan (M-CS-SA) micelles with the ability to activate the cGAS-STING signaling pathway and absorb tumor antigens were constructed. The chitosan-based nano-micelles showed valid dendritic cell (DCs) targeting and could escape from lysosomes leading to the activation of the cGAS-STING signaling pathway and the maturation of DCs. In addition, a combinatorial therapy was presented based on the programmed administration of oxaliplatin and M-CS-SA. M-CS-SA adsorbed tumor antigens released by chemotherapy to construct an autologous tumor vaccine and built a comprehensive antitumor immune response. In vivo, the combinatorial therapy achieved a tumor inhibition rate of 76.31 % at the oxaliplatin dose of 5 mg/kg and M-CS-SA dose of 15 mg/kg, and increased the CD3⁺ CD8⁺ T cell infiltration. This work demonstrated that M-CS-SA and its co-treatment with oxaliplatin showed great potential in tumor immunotherapy.

环 GMP-AMP 合酶 (cGAS)-干扰素基因刺激剂 (STING) 信号通路是调节先天性和适应性免疫反应的重要 DNA 传感通路，在肿瘤免疫治疗中发挥着重要作用。尽管可以使用 STING 激动剂，但它们由于无法靶向免疫细胞和全身免疫毒性而受到限制，需要新的策略来准确有效地激活 cGAS-STING 信号通路。在此，构建了具有激活cGAS-STING信号通路和吸收肿瘤抗原能力的甘露糖修饰的硬脂酸接枝壳聚糖（M-CS-SA）胶束。基于壳聚糖的纳米胶束显示出有效的树突状细胞（DC）靶向性，并且可以逃离溶酶体，导致 cGAS-STING 信号通路的激活和 DC 的成熟。此外，还提出了一种基于奥沙利铂和 M-CS-SA 程序化给药的组合疗法。M-CS-SA吸附化疗释放的肿瘤抗原构建自体肿瘤疫苗并建立全面的抗肿瘤免疫反应。在体内，奥沙利铂剂量5 mg/kg和M-CS-SA剂量15 mg/kg的组合治疗取得了76.31%的肿瘤抑制率，并增加了CD3+CD8+ ^T细胞^浸润。这项工作表明M-CS-SA及其与奥沙利铂的联合治疗在肿瘤免疫治疗中显示出巨大的潜力。