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Silica Nanoparticles Decorated with Ceria Quantum Dots Modulate Intra- and Extracellular Reactive Oxygen Species Formation and Selectively Reduce Human A375 Melanoma Cell Proliferation
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2024-09-16 , DOI: 10.1021/acsami.4c11483
Marcela L. Chaki Borrás, Rajib Chandra Das, Philip J. Barker, Ronald Sluyter, Konstantin Konstantinov

Nanomaterials show great promise for cancer treatment. Nonetheless, most nanomaterials lack selectivity for cancer cells, damaging healthy ones. Cerium dioxide (ceria, CeO2) nanoparticles have been shown to exert selective toxicity toward cancer cells due to the redox modulating properties they display as their size decreases. However, these particles suffer from poor suspension stability. The efficacy of CeO2 nanoparticles for cancer treatment is hampered by their innate high surface energy, which leads to particle agglomeration and, consequently, reactivity loss. This effect increases as particle size decreases; as such, quantum dots (QDs) suffer most from this phenomenon. In this study, it is proposed that silicon dioxide (silica, SiO2) nanoparticles can provide an inert platform for surface encrusted CeO2 QDs and that the resulting nanocomposite (hereafter QDCeO2/SiO2) not only will exhibit negligible agglomeration compared with CeO2 alone but also will improve the modulation of reactive oxygen species (ROS) leading to selective reduction of human A375 melanoma cell proliferation. The SiO2 nanoparticles had a bimodal size distribution with median particle size of 66 and 168 nm, while the CeO2 quantum dots encrusted on their surface had a size of 3.2 nm. An elevated Ce3+/Ce4+ ratio led to the QDCeO2/SiO2 nanocomposite displaying synergistic superoxide dismutase- and catalase-like activity, favoring the accumulation of ROS at pH 6.5 which translated into QDCeO2/SiO2 exerting selective oxidative stress in, and toward, the melanoma cells. Treatment with 50 μg mL–1 QDCeO2/SiO2 significantly reduced cell proliferation by 27% compared to untreated control cells in the colony formation assay. Treatment with either SiO2 or CeO2 alone did not affect the cell proliferation. These results highlight the benefit of dispersing CeO2 QDs on the surface of core nanoparticles and the resulting enhancement of selective redox reactivity and proliferation arrest when compared to CeO2 nanoparticles alone. Furthermore, the method employed here to encrust CeO2 QDs could lead to the facile synthesis of new nanocomposites with enhanced control of ROS activity, not only for in vitro studies using other cancer cell lines of interest but also in animal models and perhaps leading to clinical trials in melanoma patients.

中文翻译:


用二氧化铈量子点装饰的二氧化硅纳米颗粒调节细胞内和细胞外活性氧的形成并选择性减少人 A375 黑色素瘤细胞增殖



纳米材料在癌症治疗方面显示出巨大的前景。尽管如此,大多数纳米材料缺乏对癌细胞的选择性,从而损害健康细胞。二氧化铈(ceria,CeO 2 )纳米颗粒已被证明对癌细胞具有选择性毒性,因为它们随着尺寸的减小而表现出氧化还原调节特性。然而,这些颗粒的悬浮稳定性较差。 CeO 2纳米颗粒用于癌症治疗的功效因其固有的高表面能而受到阻碍,这会导致颗粒团聚,从而导致反应性损失。这种效应随着颗粒尺寸的减小而增强;因此,量子点 (QD) 受此现象影响最大。在这项研究中,提出二氧化硅(silica,SiO 2 )纳米颗粒可以为表面包覆的CeO 2 QD提供惰性平台,并且所得纳米复合材料(以下简称QD CeO 2 /SiO 2 )与单独的 CeO 2也将改善活性氧 (ROS) 的调节,从而选择性减少人 A375 黑色素瘤细胞的增殖。 SiO 2纳米粒子具有双峰尺寸分布,中值粒径为66和168 nm,而包覆在其表面上的CeO 2量子点的尺寸为3.2 nm。 Ce 3+ /Ce 4+比率升高导致QD CeO 2 /SiO 2纳米复合材料表现出协同超氧化物歧化酶和过氧化氢酶样活性,有利于 ROS 在 pH 6 下的积累。5 转化为QD CeO 2 /SiO 2 ,​​在黑色素瘤细胞中和向黑色素瘤细胞施加选择性氧化应激。在集落形成测定中,与未处理的对照细胞相比,用 50 μg mL –1 QD CeO 2 /SiO 2处理的细胞增殖显着降低了 27%。单独用SiO 2或CeO 2处理不影响细胞增殖。这些结果凸显了将CeO 2 QD分散在核心纳米粒子表面上的好处,以及与单独使用CeO 2纳米粒子相比所导致的选择性氧化还原反应性和增殖抑制的增强。此外,这里采用的包覆 CeO 2 QD 的方法可以轻松合成新型纳米复合材料,并增强对 ROS 活性的控制,不仅适用于使用其他感兴趣的癌细胞系的体外研究,而且还适用于动物模型,并可能导致临床研究在黑色素瘤患者中进行的试验。
更新日期:2024-09-16
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