Evaluation of Cytotoxicity of Gold Glyconanoparticles of Human Colon Adenocarcinoma Cells

I. V. Chernykh, Mariya A. Kopanitsa, A. V. Shchul’kin, E. Yakusheva, Andrey Yu. Ershov, A. Martynenkov, I. V. Lagoda, Alexandra M. Volkova
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Abstract

INTRODUCTION: Use of metal nanoparticles is a promising trend in oncotherapy. AIM: To evaluate cytotoxicity of gold nanoparticles (GNPs) modified with fucose, lactose and galactose residues, on Caco-2 cells. MATERIALS AND METHODS: Cells were cultured to a monolayer with GHPs in concentrations of 10 g/ml600 g/ml for particles with fucose, 10 g/ml900 g/ml for particles with lactose and 10 g/ml550 g/ml for particles with galactose. As non-tumor cells, Caco-2 cells were used after differentiation into small-intestine enterocytes (incubation time 21 days). The cytotoxicity of GNPs was evaluated in MTT-test after incubation with cells for 2 hours, 8 hours and 24 hours. A comparison drug was fluorouracil in concentrations of 50 g/ml2000 g/ml. The half-maximal inhibitory concentration (IC50) was calculated in GraphPad Prism 8.4.3 program. RESULTS: IC50 for GNPs with fucose for tumor cells was 582 29 and 336 36 g/ml after incubation for 2 hours and 8 hours, respectively; for GNPs with lactose 769 50 and 515 45 g/ml, for GNPs with galactose 467 299 and 299 28 g/ml. For differentiated cells, IC50 for all types of GNPs was higher than for tumor cells after incubation for 2 and 8 hours: for particles with fucose 530 3 and 410 15 g/ml; for particles with lactose 831 7 and 639 14 g/ml; for particles with galactose 511 21 (p = 0.018) and 376 36 g/ml, respectively. After 24-hour incubation of Caco-2 cells with fucose, IC50 did not differ for tumor and differentiated varieties. For other GNPs, IC50 for tumor cells was higher than for differentiated cells. Fluorouracil showed cytotoxicity for tumor cells with IC50 2108 19 and 1764 193 g/ml after 2 hours and 8 hours of incubation, respectively. For differentiated cells, IC50 of fluorouracil was 1694 102 g/ml after 2-hour incubation and 1694 102 g/ml after 8-hour incubation. There were no differences between IC50 of fluorouracil for differentiated and tumor cells with equal incubation time. CONCLUSION: GNPs with fucose, lactose and galactose have a cytotoxic effect on human colon adenocarcinoma cells and in the activity are superior to fluorouracil.
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金聚糖颗粒对人结肠腺癌细胞的细胞毒性评价
金属纳米颗粒在肿瘤治疗中的应用是一个很有前途的趋势。目的:评价焦糖、乳糖和半乳糖残基修饰的金纳米颗粒(GNPs)对Caco-2细胞的细胞毒性。材料与方法:用GHPs单层培养细胞,有聚焦颗粒浓度为10 g/ml600 g/ml,有乳糖颗粒浓度为10 g/ml900 g/ml,有半乳糖颗粒浓度为10 g/ml550 g/ml。作为非肿瘤细胞,Caco-2细胞分化成小肠肠细胞后使用(孵育时间21 d)。在细胞孵育2小时、8小时和24小时后,采用mtt试验评价GNPs的细胞毒性。比较药物为氟尿嘧啶,浓度为50 g/ml, 2000 g/ml。在GraphPad Prism 8.4.3程序中计算半最大抑制浓度(IC50)。结果:GNPs作用于肿瘤细胞2 h、8 h后的IC50分别为582 29、336 36 g/ml;含乳糖769 50和515 45 g/ml的GNPs,含半乳糖467 299和299 28 g/ml的GNPs。对于已分化的细胞,2小时和8小时后,所有类型GNPs的IC50均高于肿瘤细胞:聚焦颗粒为530 3和410 15 g/ml;含有乳糖831 7和639 14 g/ml的颗粒;对于含有半乳糖的颗粒,分别为511 21 (p = 0.018)和376 36 g/ml。Caco-2细胞与病灶孵育24小时后,肿瘤和分化品种的IC50无差异。其他GNPs在肿瘤细胞中的IC50值高于分化细胞。氟尿嘧啶对肿瘤细胞的杀伤作用分别为IC50 2108 19 g/ml和1764 193 g/ml。对分化细胞,孵育2小时后,氟尿嘧啶的IC50为1694 102 g/ml,孵育8小时后,IC50为1694 102 g/ml。在相同孵育时间下,氟尿嘧啶对分化细胞和肿瘤细胞的IC50值无差异。结论:带病灶GNPs、乳糖GNPs和半乳糖GNPs对人结肠腺癌细胞具有细胞毒作用,且活性优于氟尿嘧啶。
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