负载过氧化铜的介孔二氧化硅纳米粒子协同化学动力学疗法和化疗联合治疗肿瘤

Copper Peroxide Coated Mesoporous Silica Nanoparticles for Tumor Treatment by the Combination of Chemodynamic Therapy and Chemotherapy

化学动力学治疗(CDT)是通过使用芬顿催化剂将细胞内过氧化氢(H_(2)O_(2))催化成羟基自由基(·OH)以杀死癌细胞的一种新型治疗方法。然而,内源性H_(2)O_(2)含量不足以及单一治疗的局限性限制了CDT的治疗效率。本工作报道了一种负载过氧化铜(CuO_(2))的介孔二氧化硅纳米颗粒(MSN)。其中,MSN内部负载化疗药物阿霉素(DOX),其表面负载催化剂CuO_(2)封堵孔道,避免药物提前早释。在肿瘤微环境(TME)刺激下,CuO_(2)分解产生外源性H_(2)O_(2)和类芬顿离子Cu~(2+),Cu^(2+)消耗细胞内谷胱甘肽(GSH)生成Cu^(+),Cu^(+)催化外源性H_(2)O_(2)生成高细胞毒性的·OH,协同化疗药物DOX实现CDT和化疗的联合治疗,提高抗肿瘤疗效。此外,体外细胞实验研究表明,该芬顿催化剂表现出良好的细胞相容性和优异的细胞毒性,为协同治疗肿瘤提供了一种新策略。

Chemodynamic therapy is a novel method,which uses a Fenton catalyst to catalyze intracellular hydrogen peroxide into hydroxyl radicals to kill cancer cells.However,the low level of intracellular H_(2)O_(2)in tumor cells and the limitations of monotherapy limit the effective treatment performance.Here we report a kind of copper peroxide-loaded mesoporous silica nanoparticle(MSN)in which doxorubicin(DOX)was loaded into the pores,then CuO_(2)catalyst was coated on the surface of MSN to prevent the premature of drug release.Under the stimulus of the tumor microenvironment(TME),CuO_(2)was decomposed to produce hydrogen peroxide(H_(2)O_(2))and the Fenton-like ion Cu^(2+).Then,Cu^(2+)consumed the intracellular glutathione(GSH)to produce Cu+,which catalyzed H_(2)O_(2)to produce the highly cytotoxic·OH.Meanwhile,the successful delivery of DOX from MSN realizes the integration of chemodynamic therapy and chemotherapy.In addition,the experiments in vitro showed that this Fenton catalyst DOX@MSN@CuO_(2)exhibits good cytocompatibility and excellent cytotoxicity,which provides a new strategy for tumor treatment.