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Montmorillonite colloid plates with adsorbed cytochrome c: in vitro cytotoxic effect on colon cancer cell culture
Cancer Nanotechnology ( IF 5.7 ) Pub Date : 2021-08-23 , DOI: 10.1186/s12645-021-00095-7
Svetlana H. Hristova 1 , Alexandar M. Zhivkov 2
Affiliation  

The apoptosis (a cascade of biochemical reactions leading to suicide of damaged biological cells) is blocked in the cancer cells because of impossibility of cytochrome c (cytC) go out from the mitochondria. However, the apoptosis can be started by introducing of exogenous cytC into cytoplasm using colloid particles as a protein carrier due to ability of the cancer cells to phagocytize extracellular particles with submicron size. The clay mineral montmorillonite (MM) were used to prepare aqueous suspension of protein/mineral composite particles by electrostatic adsorption of the positively charged cytC globules on the negatively charged MM colloid plates, and then added to colon cancel culture. The results shows out that separately cytC and MM have no effect but the composite cytC-MM particles kill 95% of the cancer cells after 96 h treatment using equine cytC which is 97% structurally identical with the human cytC. To reach this high cytotoxicity we have formulated requirements to: (a) bare colloid particles (electric charge, form and size), (b) conditions for protein adsorption (concentrations, pH, ionic strength), and (c) suspension with the composite particles (positive total charge and optimal concentration). Due to satisfying these requirements we have reached cytotoxicity which is 1/3 higher than the reached by other authors using different artificial particles. The cytotoxicity rapidly increases with concentration of the cytC-MM particles but further it shows tendency to saturation. The optimal pH 6.5 and the 10:3 mg/mg cytC/MM concentration ratio at adsorption were found out by employing computer (protein electrostatics) and physicochemical methods (microelectrophoresis and colloid electrooptics) to prepare cytC-MM suspension. The anticancer capability of cytC-MM nanoplates were investigated using cell culture of metastasizing colon cancer. The in vitro experiments with colon cancer cell culture disclose that cytC-MM composite particles have potential for application in anticancer therapy of superficial neoplasms of the skin and the alimentary system (mouth cavity, esophagus, stomach, jejunum and colon).

中文翻译:

吸附细胞色素 c 的蒙脱石胶体板:体外对结肠癌细胞培养的细胞毒作用

由于细胞色素 c (cytC) 不可能从线粒体中排出,细胞凋亡(导致受损生物细胞自杀的一系列生化反应)在癌细胞中被阻止。然而,由于癌细胞具有吞噬亚微米大小的细胞外颗粒的能力,因此可以通过使用胶体颗粒作为蛋白质载体将外源性 cytC 引入细胞质来启动细胞凋亡。粘土矿物蒙脱石(MM)通过带正电荷的cytC小球在带负电荷的MM胶体板上静电吸附制备蛋白质/矿物质复合颗粒的水悬浮液,然后加入到结肠取消培养中。结果表明,单独的 cytC 和 MM 没有作用,但复合 cytC-MM 颗粒在使用马 cytC 处理 96 小时后杀死了 95% 的癌细胞,其结构与人 cytC 有 97% 的相同。为了达到这种高细胞毒性,我们制定了以下要求:(a)裸胶体颗粒(电荷、形状和大小),(b)蛋白质吸附条件(浓度、pH值、离子强度),以及(c)与复合材料悬浮粒子(正总电荷和最佳浓度)。由于满足这些要求,我们达到了比其他作者使用不同人工颗粒所达到的高 1/3 的细胞毒性。细胞毒性随着 cytC-MM 颗粒的浓度迅速增加,但进一步显示出饱和趋势。最佳 pH 值 6.5 和 10:通过使用计算机(蛋白质静电学)和物理化学方法(微电泳和胶体电光)制备 cytC-MM 悬浮液,发现吸附时 3 mg/mg cytC/MM 浓度比。使用转移性结肠癌的细胞培养物研究了 cytC-MM 纳米板的抗癌能力。结肠癌细胞培养体外实验表明,cytC-MM复合颗粒在皮肤和消化系统(口腔、食道、胃、空肠和结肠)浅表肿瘤的抗癌治疗中具有应用潜力。使用转移性结肠癌的细胞培养物研究了 cytC-MM 纳米板的抗癌能力。结肠癌细胞培养体外实验表明,cytC-MM复合颗粒在皮肤和消化系统(口腔、食道、胃、空肠和结肠)浅表肿瘤的抗癌治疗中具有应用潜力。使用转移性结肠癌的细胞培养物研究了 cytC-MM 纳米板的抗癌能力。结肠癌细胞培养体外实验表明,cytC-MM复合颗粒在皮肤和消化系统(口腔、食道、胃、空肠和结肠)浅表肿瘤的抗癌治疗中具有应用潜力。
更新日期:2021-08-23
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