FeO 涂层 CNTs-阿拉伯胶纳米杂化复合材料通过 ROS 介导的信号转导增强抗白血病活性，针对 AML 细胞。

BACKGROUND: Prior studies on magnetite (FeO) NPs and carbon nanotubes (CNTs) cytotoxic effects against acute myeloid leukemia (AML) are inconclusive rather than definitive. PURPOSE: Investigation of the effects of Gum Arabic (GA)-stabilized/destabilized FeO NPs and CNTs, alone or in combination, on AML cell proliferation. METHODS: Hybrid NPs were synthesized, characterized, and assessed for their cytotoxicity against Kasumi-1, HL-60, and THP-1 in comparison to normal primary bone marrow CD34 cells. The molecular pathways of nanostructures' cytotoxicity were also investigated. RESULTS: The FeO NPs were effectively synthesized and attached to the surface of the CNTs, resulting in the formation of a novel hybrid through their interaction with the GA colloidal solution in an aqueous media. Although the evaluated nanostructured nanoparticles had significant growth suppression ability against the leukemia cell lines, with IC values ranging from 42.437 to 189.842 μg/mL, they exhibited comparatively modest toxicity towards normal hematopoietic cells (IC: 113.529‒162.656 μg/mL). The incorporation of FeO NPs with CNTs in a hybrid nanocomposite significantly improved their effectiveness against leukemia cells, with the extent of improvement varying depending on the specific cell type. The nanostructured particles were stabilized by GA, which enhances their ability to inhibit cell proliferation in a manner that depends on the specific cell type. Also, nanoparticles exhibit cytotoxicity due to their capacity to stimulate the production of intracellular ROS, halt the cell cycle at the G1 phase, and induce apoptosis. This is supported by the activation of p53, BAX, cytochrome C, and caspase-3, which are triggered by ROS. The nanostructures lead to an increase in the expression of genes encoding proteins related to oxidative stress (SIRT1, FOXO3, NFE2L2, and MAP3K5) and cyclin-dependent kinase inhibitors (CDKN1A and CDKN1B) in response to ROS. CONCLUSION: We provide an effective FeO NPs/CNTs nano-hybrid composite that induces apoptosis and has strong anti-leukemic capabilities. This hybrid nanocomposite is promising for in vivo testing and validation.

背景：先前关于磁铁矿（FeO）纳米粒子和碳纳米管（CNT）对急性髓系白血病（AML）的细胞毒性作用的研究结果并不明确。

目的：研究阿拉伯树胶（GA）稳定/不稳定的 FeO 纳米粒子和 CNT 单独或联合使用对 AML 细胞增殖的影响。

方法：合成了杂化纳米粒子，对其进行了表征，并与正常原代骨髓 CD34 细胞进行了比较，评估了它们对 Kasumi-1、HL-60 和 THP-1 的细胞毒性。还研究了纳米结构细胞毒性的分子途径。

结果：成功合成了 FeO 纳米粒子，并将其附着在 CNT 的表面上，通过在水介质中与 GA 胶体溶液相互作用，形成了一种新型的杂化纳米粒子。虽然评估的纳米结构纳米粒子对白血病细胞系具有显著的生长抑制能力，其 IC 值范围为 42.437 至 189.842 μg/mL，但它们对正常造血细胞的毒性相对较小（IC：113.529 至 162.656 μg/mL）。将 FeO 纳米粒子与 CNT 结合在杂化纳米复合材料中，显著提高了它们对白血病细胞的作用，其增强程度取决于特定的细胞类型。GA 稳定了纳米结构颗粒，增强了它们抑制细胞增殖的能力，这种能力取决于特定的细胞类型。此外，纳米颗粒还通过刺激细胞内 ROS 的产生、使细胞周期停滞在 G1 期并诱导细胞凋亡来发挥细胞毒性作用。这得到了 ROS 触发的 p53、BAX、细胞色素 C 和 caspase-3 的激活的支持。纳米结构导致与氧化应激相关的蛋白质（SIRT1、FOXO3、NFE2L2 和 MAP3K5）和细胞周期蛋白依赖性激酶抑制剂（CDKN1A 和 CDKN1B）的编码基因表达增加，以响应 ROS。

结论：我们提供了一种有效的 FeO NPs/CNTs 纳米杂化复合材料，它能诱导细胞凋亡并具有强大的抗白血病能力。这种杂化纳米复合材料有望进行体内测试和验证。