School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China.
Clinical Research Institute, The First People's Hospital of Foshan & Sun Yat-sen University Foshan Hospital, Foshan, 528000, China.
Biomaterials. 2022 May;284:121503. doi: 10.1016/j.biomaterials.2022.121503. Epub 2022 Mar 29.
Tumor cells reprogram the metabolic pathways to acquire abundant nutrients and sustain malignant proliferation. This fierce metabolic competition in tumor ecosystem has been uncovered to be associated with tumor microenvironmental immunosuppression. Here we develop an adenosine triphosphate (ATP)-exhausted nanocomplex (IR@ZIF-RGD) to intervene in tumor energy metabolism and regulate tumor immune microenvironment. IR@ZIF-RGD could effectively deplete intracellular ATP and inhibit ATP synthesis by ATP-responsive ZIF-90 and siRNA targeting thioredoxin reductase-2, respectively, thus leading to tumor metabolism disorders and immunosuppressive reversion. Meanwhile, IR@ZIF-RGD induced oxidative stress and ICG triggered photothermal therapy could provoke potent immunogenic cell death to enhance antitumor immunogenicity. Such a photo-immunometabolic nanocomplex has been demonstrated to be an efficient vaccine to elicit protective anticancer immune response in vivo, achieving suppressed growth of both primary and abscopal tumors, as well as inhibited tumor metastasis.
肿瘤细胞重新编程代谢途径以获取丰富的营养物质并维持恶性增殖。肿瘤生态系统中的这种激烈代谢竞争已被发现与肿瘤微环境免疫抑制有关。在这里，我们开发了一种三磷酸腺苷（ATP）耗竭纳米复合物（IR@ZIF-RGD）来干预肿瘤能量代谢并调节肿瘤免疫微环境。IR@ZIF-RGD 能够通过 ATP 响应型 ZIF-90 和针对硫氧还蛋白还原酶 2 的 siRNA 分别有效耗尽细胞内 ATP 并抑制 ATP 合成，从而导致肿瘤代谢紊乱和免疫抑制逆转。同时，IR@ZIF-RGD 诱导的氧化应激和 ICG 触发的光热治疗可以引发强烈的免疫原性细胞死亡，从而增强抗肿瘤免疫原性。这种光免疫代谢纳米复合物已被证明是一种有效的疫苗，可在体内引发保护性抗癌免疫反应，抑制原发性和远隔肿瘤的生长，并抑制肿瘤转移。
