Chaki Borrás Marcela L, Das Rajib Chandra, Barker Philip J, Sluyter Ronald, Konstantinov Konstantin
Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong, 2500 North Wollongong, New South Wales, Australia.
Illawarra Health and Medical Research Institute, University of Wollongong, 2500 North Wollongong, New South Wales, Australia.
ACS Appl Mater Interfaces. 2024 Sep 25;16(38):50430-50441. doi: 10.1021/acsami.4c11483. Epub 2024 Sep 16.
Nanomaterials show great promise for cancer treatment. Nonetheless, most nanomaterials lack selectivity for cancer cells, damaging healthy ones. Cerium dioxide (ceria, CeO) 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 CeO 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, SiO) nanoparticles can provide an inert platform for surface encrusted CeO QDs and that the resulting nanocomposite (hereafter CeO/SiO) not only will exhibit negligible agglomeration compared with CeO alone but also will improve the modulation of reactive oxygen species (ROS) leading to selective reduction of human A375 melanoma cell proliferation. The SiO nanoparticles had a bimodal size distribution with median particle size of 66 and 168 nm, while the CeO quantum dots encrusted on their surface had a size of 3.2 nm. An elevated Ce/Ce ratio led to the CeO/SiO nanocomposite displaying synergistic superoxide dismutase- and catalase-like activity, favoring the accumulation of ROS at pH 6.5 which translated into CeO/SiO exerting selective oxidative stress in, and toward, the melanoma cells. Treatment with 50 μg mL CeO/SiO significantly reduced cell proliferation by 27% compared to untreated control cells in the colony formation assay. Treatment with either SiO or CeO alone did not affect the cell proliferation. These results highlight the benefit of dispersing CeO QDs on the surface of core nanoparticles and the resulting enhancement of selective redox reactivity and proliferation arrest when compared to CeO nanoparticles alone. Furthermore, the method employed here to encrust CeO QDs could lead to the facile synthesis of new nanocomposites with enhanced control of ROS activity, not only for studies using other cancer cell lines of interest but also in animal models and perhaps leading to clinical trials in melanoma patients.
纳米材料在癌症治疗方面显示出巨大的潜力。尽管如此，大多数纳米材料对癌细胞缺乏选择性，会损害健康细胞。二氧化铈（氧化铈，CeO）纳米颗粒由于其尺寸减小后所表现出的氧化还原调节特性，已被证明对癌细胞具有选择性毒性。然而，这些颗粒的悬浮稳定性较差。CeO纳米颗粒用于癌症治疗的功效受到其固有的高表面能的阻碍，这会导致颗粒团聚，进而导致反应活性丧失。随着颗粒尺寸减小，这种效应会增强；因此，量子点（QDs）受此现象影响最为严重。在本研究中，提出二氧化硅（硅胶，SiO）纳米颗粒可为表面包覆CeO量子点提供一个惰性平台，并且由此产生的纳米复合材料（以下简称CeO/SiO）不仅与单独的CeO相比团聚可忽略不计，而且还将改善活性氧（ROS）的调节，导致人A375黑色素瘤细胞增殖的选择性降低。SiO纳米颗粒具有双峰尺寸分布，中位粒径分别为66和168 nm，而包覆在其表面的CeO量子点尺寸为3.2 nm。Ce/Ce比率升高导致CeO/SiO纳米复合材料表现出协同的超氧化物歧化酶和过氧化氢酶样活性，有利于在pH 6.5时ROS的积累，这转化为CeO/SiO在黑色素瘤细胞中并对其施加选择性氧化应激。在集落形成试验中，用50 μg/mL CeO/SiO处理与未处理的对照细胞相比，显著降低了27%的细胞增殖。单独用SiO或CeO处理均不影响细胞增殖。这些结果突出了将CeO量子点分散在核心纳米颗粒表面的益处，以及与单独的CeO纳米颗粒相比，由此产生的选择性氧化还原反应性增强和增殖停滞。此外，这里采用的包覆CeO量子点的方法可能会导致轻松合成具有增强的ROS活性控制的新型纳米复合材料，不仅适用于使用其他感兴趣的癌细胞系的研究，也适用于动物模型，甚至可能导致黑色素瘤患者的临床试验。
