Coupling tumor necrosis factor-related apoptosis-inducing ligand to iron oxide nanoparticles increases its apoptotic activity on HCT116 and HepG2 malignant cells: effect of magnetic core size

Hanene Belkahla, Amranul Haque, Alexander Revzin, Tijani Gharbi, Andrei Alexandru Constantinescu, Olivier Micheau, Miryana Hémadi, Souad Ammar
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引用次数: 6

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been considered as a potential anticancer agent owing to its selectivity for malignant cells. However, its clinical use remains limited because of its poor efficacy. Attempts to increase its antitumor activity include, among others, its functionalization by nanoparticles (NPs). In the present study, TRAIL was grafted onto magnetic spinel iron oxide NPs of defined core size, 10 and 100 nm on average, to see whether the size of the resulting nanovectors, NV10 and NV100, respectively, might affect TRAIL efficacy and selectivity. Apoptosis induced by NV10 and NV100 was higher than by TRAIL alone in both HCT116 and HepG2 cells. At equimolar concentrations, neither the nanovectors nor the corresponding NPs displayed cytotoxicity towards normal primary hepatocytes or TRAIL receptor-deficient HCT116 cells. NV100 exhibited superior proapoptotic activity than NV10, as evidenced by methylene blue and annexin V staining. Consistently, both caspase activation and TRAIL death-induced signaling complex formation, as assessed by immunoblot analysis, were found to be increased in cells treated with NV100 as compared with NV10 or TRAIL alone. These results suggest that the size of NPs is important when TRAIL is vectorized for cancer therapy.

Abstract Image

将肿瘤坏死因子相关的凋亡诱导配体与氧化铁纳米颗粒偶联可增加其对HCT116和HepG2恶性细胞的凋亡活性:磁芯大小的影响
肿瘤坏死因子相关凋亡诱导配体(TRAIL)因其对恶性细胞的选择性而被认为是一种潜在的抗癌剂。然而,由于其疗效不佳,其临床应用仍然有限。增加其抗肿瘤活性的尝试包括通过纳米颗粒(NP)对其进行功能化。在本研究中,将TRAIL接枝到具有确定核心尺寸(平均为10和100nm)的磁性尖晶石氧化铁NP上,以观察所得纳米载体NV10和NV100的尺寸是否分别会影响TRAIL的功效和选择性。NV10和NV100诱导的HCT116和HepG2细胞凋亡均高于TRAIL单独诱导的细胞凋亡。在等摩尔浓度下,纳米载体和相应的NP均未显示出对正常原代肝细胞或TRAIL受体缺陷型HCT116细胞的细胞毒性。亚甲蓝和膜联蛋白V染色证明,NV100表现出比NV10更好的促凋亡活性。一致地,通过免疫印迹分析评估,在用NV100处理的细胞中,与单独的NV10或TRAIL相比,胱天蛋白酶激活和TRAIL死亡诱导的信号复合物形成都增加。这些结果表明,当TRAIL被矢量化用于癌症治疗时,NP的大小是重要的。
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