Prajapati Neela, Karan Anik, Khezerlou Elnaz, DeCoster Mark A
Department of Biomedical Engineering, Louisiana Tech University, Ruston, LA, United States.
Institute for Micromanufacturing, Louisiana Tech University, Ruston, LA, United States.
Front Chem. 2021 Jan 27;8:629835. doi: 10.3389/fchem.2020.629835. eCollection 2020.
Copper high aspect ratio structures (CuHARS) and silver cystine nanoparticles (AgCysNPs) are two unique micro/nano particles under study here that show extensive anti-cancer effects on a glioma tumor cell line. These micro/nano particles have shown potent toxicity in the presence of inflammatory stimulus (combination of tumor necrosis factor, [TNF] and lipo-polysaccharide, LPS). CuHARS with a concentration of 20 μg/ml uniquely increased the catalytic generation of nitric oxide (NO), an important contributor in the immune system. This NO was generated in a cell culture tumor microenvironment (TME) in the presence of 25 µM S-nitrosothiol (cysteine-NO) and the inflammatory stimulus. CuHARS increased the NO production by 68.75% when compared to untreated glioma cells with CysNO and inflammatory stimulus. The production of NO was significantly higher under similar circumstances in the case of normal primary structural cells like brain microvascular endothelial cells (BMVECs). The production of NO by BMVECs went up by 181.25% compared to glioma cells. This significant increase in the NO concentration could have added up to tumorigenesis but the anti-cancer effect of CuHARS was prominent enough to lower down the viability of glioma cells by approximately 20% and increased the metabolism of structural cells, BMVECs by approximately 200%. The immunomodulatory effect of NO in the TME under these circumstances in the presence of the novel micro/nano material, CuHARS has risen up compared to the effect of inflammatory stimulus alone. The potency and specific nature of these materials toward tumor cells may make them suitable candidates for cancer treatment. Successive treatment of CuHARS to glioma cells also proved to be an effective approach considering the decrease in the total count of cells by 11.84 fold in case of three successive treatments compared to a single dose which only decreased the cell count by 2.45 fold showing the dose-dependent increasing toxicity toward glioma cells. AgCysNPs are another potent nanomaterial which also proved its significant toxic nature toward tumor cell lines as demonstrated here, but their immunomodulatory response is still unclear and needs to be explored further.
铜高纵横比结构（CuHARS）和银胱氨酸纳米颗粒（AgCysNPs）是本文正在研究的两种独特的微/纳米颗粒，它们对胶质瘤肿瘤细胞系显示出广泛的抗癌作用。这些微/纳米颗粒在存在炎性刺激（肿瘤坏死因子[TNF]和脂多糖[LPS]的组合）时表现出强大的毒性。浓度为20μg/ml的CuHARS独特地增加了一氧化氮（NO）的催化生成，NO是免疫系统中的一个重要成分。这种NO是在存在25μM S-亚硝基硫醇（半胱氨酸-NO）和炎性刺激的细胞培养肿瘤微环境（TME）中生成的。与未用CysNO和炎性刺激处理的胶质瘤细胞相比，CuHARS使NO产量增加了68.75%。在类似情况下，对于像脑微血管内皮细胞（BMVECs）这样的正常原代结构细胞，NO的产量显著更高。与胶质瘤细胞相比，BMVECs产生的NO增加了181.25%。NO浓度的这种显著增加本可能促进肿瘤发生，但CuHARS的抗癌作用足够显著，可使胶质瘤细胞的活力降低约20%，并使结构细胞BMVECs的代谢增加约200%。在这些情况下，在存在新型微/纳米材料CuHARS的情况下，TME中NO的免疫调节作用相比于单独的炎性刺激有所增强。这些材料对肿瘤细胞的效力和特异性可能使其成为癌症治疗的合适候选物。考虑到连续三次处理后细胞总数减少了11.84倍，而单次剂量仅使细胞计数减少了2.45倍，显示出对胶质瘤细胞的剂量依赖性毒性增加，对胶质瘤细胞连续进行CuHARS处理也被证明是一种有效的方法。AgCysNPs是另一种强大的纳米材料，此处也证明了其对肿瘤细胞系具有显著的毒性，但它们的免疫调节反应仍不清楚，需要进一步探索。
