State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown Heights, 10598, NY, USA.
Nat Commun. 2018 Nov 19;9(1):4861. doi: 10.1038/s41467-018-07257-z.
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 O 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.
静脉内给予药理剂量的抗坏血酸已被提议作为一种潜在的抗肿瘤治疗方法；然而，由于其自动氧化速度较慢，其治疗效果受到限制。在这里，我们报告钯（Pd）纳米晶体具有内在的氧化酶样活性，可加速抗坏血酸的自动氧化，从而增强其抗肿瘤功效。Pd 纳米晶体的氧化酶样活性与晶面依赖性有关，由高指数晶面封闭的凹面纳米结构比由低指数晶面封闭的平面纳米结构更有效地催化抗坏血酸的自动氧化。我们的第一性原理计算为 O 分子的晶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实验证明了这些 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，联合使用抗坏血酸和 Pd 凹面纳米立方体的方法比目前可用的临床药物具有更好的疗效，对正常细胞没有明显的细胞毒性。
