Yadav Nisha, Sharma Kikku, Sengupta Souvik, Singh Sanjay
Division of Biological and Life Sciences, School of Arts and Sciences, Central Campus, Ahmedabad University, Navrangpura, Ahmedabad, Gujarat 380009 India.
National Institute of Animal Biotechnology (NIAB), Opposite Journalist Colony, Near Gowlidoddy, Extended Q-City Road, Gachibowli, Hyderabad, Telangana 500032 India.
3 Biotech. 2023 Dec;13(12):413. doi: 10.1007/s13205-023-03813-7. Epub 2023 Nov 22.
Globally, Leishmaniasis affects underprivileged communities of the nations and chemotherapy remains one of the preferred treatment options. However, the cytotoxicity, side effects, and cost of the present chemotherapies limit their utilization. Auranofin [an organogold compound having significant structural similarity with triethyl-phosphine (TEP)] has been reported as an effective therapy for Leishmaniasis treatment. Considering the high cost of gold and the strong affinity of cerium oxide nanoparticles (CeNPs) to phosphine ligands, we designed TEP-decorated CeNPs (CeNPs-TEP) and used them as a novel antileishmanial agent. The hydrodynamic size of synthesized CeNPs and CeNPs-TEP was observed to be 22.2 ± 3.7 nm and 92.11 ± 6.2 nm, respectively. CeNPs-TEP provided aqueous stability to TEP as TEP alone is extremely unstable in water. Exposure of CeNPs-TEP showed ~ 60 and ~ 82% cell death in Ag83 promastigotes after 24 and 48 h, respectively. The same concentration of CeNPs-TEP did not affect the cellular viability of RAW 264.7 macrophage cells significantly. The oxidative stress and depolarization of the mitochondrial membrane were also observed after the treatment of CeNPs-TEP. Exposure of CeNPs-TEP induced a ~ 2.2-fold increase in ROS generation inside Ag83 cells. Dual staining with ethidium bromide and acridine orange reveals that these processes ultimately result in cell death. The results conclude that a combination of CeNPs and TEP could open the door for developing novel antileishmanial therapeutics in the future.
The online version contains supplementary material available at 10.1007/s13205-023-03813-7.
在全球范围内,利什曼病影响着各国的贫困社区,化疗仍然是首选的治疗选择之一。然而,目前化疗的细胞毒性、副作用和成本限制了它们的应用。金诺芬[一种与三乙膦(TEP)具有显著结构相似性的有机金化合物]已被报道为治疗利什曼病的有效疗法。考虑到金的高成本以及氧化铈纳米颗粒(CeNPs)对膦配体的强亲和力,我们设计了TEP修饰的CeNPs(CeNPs-TEP)并将其用作新型抗利什曼原虫剂。观察到合成的CeNPs和CeNPs-TEP的流体动力学尺寸分别为22.2±3.7nm和92.11±6.2nm。CeNPs-TEP为TEP提供了水相稳定性,因为单独的TEP在水中极不稳定。暴露于CeNPs-TEP后,Ag83前鞭毛体在24小时和48小时后分别显示约60%和约82%的细胞死亡。相同浓度的CeNPs-TEP对RAW 264.7巨噬细胞的细胞活力没有显著影响。在CeNPs-TEP处理后还观察到氧化应激和线粒体膜去极化。暴露于CeNPs-TEP会导致Ag83细胞内活性氧生成增加约2.2倍。用溴化乙锭和吖啶橙进行双重染色表明,这些过程最终导致细胞死亡。结果表明,CeNPs和TEP的组合可能为未来开发新型抗利什曼病治疗方法打开大门。
在线版本包含可在10.1007/s13205-023-03813-7获取的补充材料。