A hydrogen peroxide economizer for on-demand oxygen production-assisted robust sonodynamic immunotherapy.
A hydrogen peroxide economizer for on-demand oxygen production-assisted robust sonodynamic immunotherapy.
复制标题
用于按需产氧辅助的稳健声动力免疫疗法的过氧化氢节约器
作者：
Jiang Q;Qiao B;Lin X;Cao J;Zhang N;Guo H;Liu W;Zhu L;Xie X;Wan L;Tang R;Liang B;Wang D;Wang Z;Zhou Y;Ran H;Li P
声动力学免疫疗法的结果受到肿瘤缺氧的显着限制。为了克服这一障碍，一种常见的解决方案是催化内源性 H2O2 转化为 O2。然而，该策略的有效性受到肿瘤微环境（TME）中H2O2浓度不足的限制。在此，我们开发了一种 H2O2 节约器，用于在超声激活过程中按需供应 O2 和声敏剂介导的活性氧产生，从而减轻缺氧相关的限制并增强声动力免疫疗法的功效。方法：通过Fe掺杂聚二氨基吡啶（Fe-PDAP）纳米酶与二氢卟酚e6之间的静电吸附和π-π相互作用构建H2O2省煤器。通过对癌细胞膜采用仿生工程策略，我们解决了过早渗漏问题并增加了纳米颗粒（膜包被的 Fe-PDAP/Ce6、MFC）在肿瘤部位的积累。结果：所制备的MFC可以通过减少Fe-PDAP与H2O2的接触来显着减弱Fe-PDAP的催化活性。超声波照射促进了 MFC 的解离和 Fe-PDAP 的暴露，以获得更强劲的 O2 供应。此外，MFC增强声动力疗法与抗程序性细胞死亡蛋白1抗体（aPD-1）免疫检查点阻断相结合，可诱导针对原发肿瘤和远处肿瘤的强烈抗肿瘤反应。结论：这种制备的 H2O2 节约器通过减少 H2O2 消耗显着缓解肿瘤缺氧，按需增氧声动力免疫疗法可以有效对抗肿瘤。
The outcome of sonodynamic immunotherapy is significantly limited by tumor hypoxia. To overcome this obstacle, one common solution is to catalyze the conversion of endogenous H2O2 into O2. However, the effectiveness of this strategy is limited by the insufficient concentration of H2O2 in the tumor microenvironment (TME). Herein, we developed a H2O2 economizer for on-demand O2 supply and sonosensitizer-mediated reactive oxygen species production during ultrasound activation, thereby alleviating hypoxia-associated limitations and augmenting the efficacy of sonodynamic immunotherapy. Methods: The H2O2 economizer is constructed by electrostatic adsorption and π-π interactions between the Fe-doped polydiaminopyridine (Fe-PDAP) nanozyme and chlorin e6. By employing a biomimetic engineering strategy with cancer cell membranes, we addressed the premature leakage issue and increased tumor-site accumulation of nanoparticles (membrane-coated Fe-PDAP/Ce6, MFC). Results: The prepared MFC could significantly attenuate the catalytic activity of Fe-PDAP by reducing their contact with H2O2. Ultrasound irradiation promoted MFC dissociation and the exposure of Fe-PDAP for a more robust O2 supply. Moreover, the combination of MFC-enhanced sonodynamic therapy with anti-programmed cell death protein-1 antibody (aPD-1) immune checkpoint blockade induced a strong antitumor response against both primary tumors and distant tumors. Conclusion: This as-prepared H2O2 economizer significantly alleviates tumor hypoxia via reducing H2O2 expenditure and that on-demand oxygen-elevated sonodynamic immunotherapy can effectively combat tumors.
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DOI：
10.1002/advs.202001983
发表时间：
2020-01
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
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