The immunosuppressive microenvironment of malignant tumors severely hampers the effectiveness of anti-tumor therapy. Moreover, abnormal tumor vasculature interacts with immune cells, forming a vicious cycle that further interferes with anti-tumor immunity and promotes tumor progression. Our pre-basic found excellent anti-tumor effects of -di-AMP and RRx-001, respectively, and we further explored whether they could be combined synergistically for anti-tumor immunotherapy. We chose to load these two drugs on PVA-TSPBA hydrogel scaffolds that expressly release drugs within the tumor microenvironment by in situ injection. Studies have shown that -di-AMP activates the STING pathway, enhances immune cell infiltration, and reverses tumor immunosuppression. Meanwhile, RRx-001 releases nitric oxide, which increases oxidative stress injury in tumor cells and promotes apoptosis. Moreover, the combination of the two presented more powerful pro-vascular normalization and reversed tumor immunosuppression than the drug alone. This study demonstrates a new design option for anti-tumor combination therapy and the potential of tumor environmentally responsive hydrogel scaffolds in combination with anti-tumor immunotherapy.

中文翻译：

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环境响应性水凝胶促进血管正常化，增强 STING 抗肿瘤免疫力


恶性肿瘤的免疫抑制微环境严重阻碍了抗肿瘤治疗的有效性。而且，异常的肿瘤血管系统与免疫细胞相互作用，形成恶性循环，进一步干扰抗肿瘤免疫，促进肿瘤进展。我们的预基础发现-di-AMP和RRx-001分别具有优异的抗肿瘤作用，我们进一步探讨了它们是否可以协同联合用于抗肿瘤免疫治疗。我们选择将这两种药物负载在 PVA-TSPBA 水凝胶支架上，通过原位注射在肿瘤微环境中明确释放药物。研究表明-di-AMP可激活STING通路，增强免疫细胞浸润，逆转肿瘤免疫抑制。同时，RRx-001释放一氧化氮，增加肿瘤细胞的氧化应激损伤并促进细胞凋亡。此外，两者的组合比单独使用药物具有更强大的促血管正常化和逆转肿瘤免疫抑制的作用。这项研究展示了抗肿瘤联合疗法的新设计选择以及肿瘤环境响应性水凝胶支架与抗肿瘤免疫疗法相结合的潜力。