Boosting tumor treatment by dredging the hurdles of chemodynamic therapy synergistic ion therapy
Boosting tumor treatment by dredging the hurdles of chemodynamic therapy synergistic ion therapy
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疏通化学动力学疗法协同离子疗法的障碍，促进肿瘤治疗
DOI：
10.1016/j.cej.2021.128440
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发表时间：
2021-01-16
影响因子：
15.1
通讯作者：
Shi, Jinjin
中科院分区：
文献类型：
--
作者：
Liu, Junjie;Jin, Yajie;Shi, Jinjin
化疗动力学疗法（chemodynamic therapy， CDT）虽然具有不需要O-2参与而产生羟基自由基（中心点OH）的肿瘤治疗优势，但H2O2不足和Fe离子循环受阻仍是其临床应用的主要障碍。在此，我们开发了一种具有H2O2自供应和铁离子自循环特性的混合纳米颗粒，用于增强CDT。通过ZIF-8包埋CaO2，并在表面原位组装Fe3+/TA（单宁酸），制备了杂化纳米粒子CaO2@ZIF8@MPN。Fe3+/TA包被在溶酶体酸性条件下解离，释放Fe3+和TA。值得注意的是，未受保护的CaO2可以降解为H2O2和Ca2+，为CDT提供足够的材料，并产生离子治疗的Ca2+“风暴”。同时，TA可以将Fe3+转化为Fe2+，实现自循环，促进中心点OH的持续生成。有趣的是，Fe3+/TA涂层赋予纳米颗粒光热性质，加速了降解，进一步提高了Fenton反应的效率，在荷瘤小鼠中获得了77.7%的肿瘤生长抑制率，且无明显不良反应。我们的研究结果表明CaO2@ZIF8@MPN具有应用于增强CDT协同抗肿瘤离子治疗的潜力。
Although chemodynamic therapy (CDT) holds the advantage of tumor treatment by generating hydroxyl radicals (center dot OH) without the participation of O-2, insufficient H2O2 and the hindered Fe ion circulation remain major hurdles for its clinical application. Herein, we developed a hybrid nanoparticle with H2O2 self-supply and iron ion selfcirculation properties for enhanced CDT. Through encapsulation of CaO2 with ZIF-8 and in situ assembled Fe3+/TA (tannic acid) on the surface, the hybrid nanoparticles (CaO2@ZIF8@MPN) were prepared. The Fe3+/TA coating could dissociate in response to lysosomal acidity, and release Fe3+ and TA subsequently. Significantly, the unprotected CaO2 can be degraded to H2O2 and Ca2+, providing sufficient materials for CDT and resulting in a Ca2+ "storm" for ion therapy. Meanwhile, TA could convert Fe3+ to Fe2+, realizing a self-circulation for promoting the sustained generation of center dot OH. Interestingly, Fe3+/TA coating endows the nanoparticles with photothermal property, which accelerated the degradation and further improved the efficiency of Fenton reaction, obtaining 77.7% of tumor growth inhibited rate without obvious adverse effect in tumor-bearing mice. Our findings showed CaO2@ZIF8@MPN had potential to be applied for enhanced CDT synergistic antitumor ion therapy.