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Palladium concave nanocrystals with high-index facets accelerate ascorbate oxidation in cancer treatment

机译:高折射率刻面的钯凹面纳米晶体在癌症治疗中加速抗坏血酸的氧化

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摘要

Intravenous pharmacological dose of ascorbate has been proposed as a potential antitumor therapy; however, its therapeutic efficacy is limited due to the slow autoxidation. Here, we report that palladium (Pd) nanocrystals, which possess intrinsic oxidase-like activity, accelerate the autoxidation of ascorbate, leading to the enhancement of its antitumor efficacy. The oxidase-like activity of Pd nanocrystals was facet-dependent, with the concave nanostructure enclosed by high-index facets catalyzing ascorbate autoxidation more efficiently than the planar nanostructure enclosed by low-index facets. Our first-principles calculations provide the underlying molecular mechanisms for the facet-dependent activation of O2 molecule and subsequent ascorbate oxidation. Further in vitro and in vivo assays demonstrate the enhancement of the antitumor efficacy of ascorbate with these Pd concave nanocubes. Our animal experiments also indicate the combined approach with both ascorbate and Pd concave nanocubes displays an even better efficacy than currently available clinical medicines, with no obvious cytotoxicity to normal cells.
机译:静脉注射抗坏血酸的药理学剂量已被建议作为一种潜在的抗肿瘤疗法。然而,由于缓慢的自氧化作用,其治疗效果有限。在这里,我们报道具有固有的氧化酶样活性的钯(Pd)纳米晶体可加速抗坏血酸的自氧化,从而增强其抗肿瘤功效。 Pd纳米晶体的氧化酶样活性是依赖于小平面的,高折射率小平面包围的凹面纳米结构比低折射率小平面包围的平面纳米结构更有效地催化抗坏血酸自氧化。我们的第一原理计算为O2分子的面依赖性活化和随后的抗坏血酸氧化提供了潜在的分子机制。进一步的体外和体内试验证明了这些Pd凹面纳米立方体增强了抗坏血酸的抗肿瘤功效。我们的动物实验还表明,与抗坏血酸和Pd凹面纳米立方联合使用的方法比目前的临床药物具有更好的疗效,并且对正常细胞没有明显的细胞毒性。

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