通过纳米螯合技术合成的MSc1纳米复合物对实验性自身免疫性脑脊髓炎C57/BL6小鼠的治疗作用。
The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice.
作者信息
Fakharzadeh Saideh, Sahraian Mohammad Ali, Hafizi Maryam, Kalanaky Somayeh, Masoumi Zahra, Mahdavi Mehdi, Kamalian Nasser, Minagar Alireza, Nazaran Mohammad Hassan
机构信息
Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.
MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
Int J Nanomedicine. 2014 Aug 11;9:3841-53. doi: 10.2147/IJN.S64630. eCollection 2014.
PURPOSE
Currently approved therapies for multiple sclerosis (MS) at best only slow down its progression. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In the present study, for the first time we evaluated the therapeutic potential of MSc1 nanocomplex, which was designed based on novel nanochelating technology.
MATERIALS AND METHODS
MSc1 cell-protection capacity, with and without iron bond, was evaluated against hydrogen peroxide (H2O2)-induced oxidative stress in cultured rat pheochromocytoma-12 cells. The ability of MSc1 to maintain iron bond at pH ranges of 1-7 was evaluated. Nanocomplex toxicity was examined by estimating the intraperitoneal median lethal dose (LD50). Experimental autoimmune encephalomyelitic mice were injected with MSc1 14 days after disease induction, when the clinical symptoms appeared. The clinical score, body weight, and disease-induced mortality were monitored until day 54. In the end, after collecting blood samples for assessing hemoglobin and red blood cell count, the brains and livers of the mice were isolated for hematoxylin and eosin staining and analysis of iron content, respectively.
RESULTS
The results showed that MSc1 prevented H2O2-induced cell death even after binding with iron, and it preserved its bond with iron constant at pH ranges 1-7. The nanocomplex intraperitoneal LD50 was 1,776.59 mg/kg. MSc1 prompted therapeutic behavior and improved the disabling features of experimental autoimmune encephalomyelitis, which was confirmed by decreased clinical scores versus increased body mass and 100% survival probability. It did not cause any adverse effects on hemoglobin or red blood cell count. Histopathological studies showed no neural loss or lymphocyte infiltration in MSc1-treated mice, while the hepatic iron content was also normal.
CONCLUSION
These results demonstrate that MSc1 could be a promising beneficial novel agent and has the capacity to be evaluated in further studies.
目的
目前获批用于治疗多发性硬化症(MS)的疗法充其量只能减缓其病情进展。因此,有必要利用新技术来合成智能多功能结构。在本研究中,我们首次评估了基于新型纳米螯合技术设计的MSc1纳米复合物的治疗潜力。
材料与方法
评估了有铁键和无铁键的MSc1对培养的大鼠嗜铬细胞瘤-12细胞中过氧化氢(H2O2)诱导的氧化应激的细胞保护能力。评估了MSc1在pH值为1 - 7范围内保持铁键的能力。通过估计腹腔内半数致死剂量(LD50)来检测纳米复合物的毒性。在疾病诱导后14天,当临床症状出现时,给实验性自身免疫性脑脊髓炎小鼠注射MSc1。监测临床评分、体重和疾病诱导的死亡率直至第54天。最后,在采集血液样本以评估血红蛋白和红细胞计数后,分离小鼠的大脑和肝脏,分别进行苏木精和伊红染色以及铁含量分析。
结果
结果表明,即使与铁结合后,MSc1仍能防止H2O2诱导的细胞死亡,并且在pH值为1 - 7的范围内保持其与铁的结合稳定。纳米复合物的腹腔LD50为1,776.59 mg/kg。MSc1促进了治疗作用,并改善了实验性自身免疫性脑脊髓炎的致残特征,这通过临床评分降低、体重增加和100%的生存概率得到证实。它对血红蛋白或红细胞计数没有造成任何不良影响。组织病理学研究表明,接受MSc1治疗的小鼠没有神经损失或淋巴细胞浸润,同时肝脏铁含量也正常。
结论
这些结果表明,MSc1可能是一种有前景的有益新型药物,并有能力在进一步研究中进行评估。