School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin, 300350, China.
Small. 2024 Nov;20(46):e2402308. doi: 10.1002/smll.202402308. Epub 2024 Aug 8.
Metalloimmunotherapy has achieved great preclinical success against malignant tumors. Nonetheless, the limited immune cell infiltration and impaired immunogenicity within the tumor microenvironment (TME) significantly hinder its translation to clinical applications. In this study, a zinc coordination lipid nanoparticle is developed loaded with calcium peroxide hydrate (CaO) nanoparticles and the STING agonist diABZI-2, which is termed A-CaO-Zn-LNP. The release of Zn from the A-CaO-Zn-LNP and the calcium overload synergistically induced immunogenic cell death (ICD). In addition, CaO nanoparticles can consume H and release oxygen (O) under acidic conditions. This treatment increased the pH and alleviated the hypoxia of the TME. Along with cGAS-STING activation by diABZI-2, A-CaO-Zn-LNP ultimately results in enhanced anti-tumor systemic immunity and long-term immune memory via alleviating the immunosuppressive microenvironment. Taken together, A-CaO-Zn-LNP offers a new nanoplatform that expands its application for cancer treatment by metalloimmunotheray.
金属免疫疗法在对抗恶性肿瘤方面取得了巨大的临床前成功。然而，肿瘤微环境（TME）中免疫细胞浸润受限和免疫原性受损严重阻碍了其向临床应用的转化。在这项研究中，开发了一种负载过氧水合钙（CaO）纳米颗粒和 STING 激动剂二 ABZI-2 的锌配位脂质纳米颗粒，称为 A-CaO-Zn-LNP。A-CaO-Zn-LNP 中 Zn 的释放和钙超载协同诱导免疫原性细胞死亡（ICD）。此外，CaO 纳米颗粒在酸性条件下可以消耗 H 并释放氧（O）。这种治疗方法增加了 pH 值并缓解了 TME 的缺氧。随着二 ABZI-2 激活 cGAS-STING，A-CaO-Zn-LNP 通过减轻免疫抑制微环境最终导致增强的抗肿瘤全身免疫和长期免疫记忆。总之，A-CaO-Zn-LNP 提供了一种新的纳米平台，通过金属免疫疗法扩展了其在癌症治疗中的应用。
