Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran.
Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Ultrason Sonochem. 2018 May;43:248-261. doi: 10.1016/j.ultsonch.2018.01.022. Epub 2018 Jan 31.
In this work, a magnetic bio-metal-organic framework (MBMOF) nanocomposite with porous-layer open morphology is synthesized through a simple sonochemical approach and its effects on Leishmania major (MRHO/IR/75/ER) under both in vitro and in vivo conditions are investigated. The effects of sonication time, initial concentration of reagents and sonication power on size and morphology of MBMOF nanocomposites have been investigated and optimized. A comparison was then made between the structural information of the nanostructures and that of the bio-metal-organic framework crystals. Using the powder X-ray diffraction (PXRD), field emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), energy dispersive analysis of X-ray (EDAX), vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA), and Brunauer-Emmet-Teller (BET) techniques, the prepared MBMOF nanocomposites were characterized. The mean numbers of promastigotes (cell/ml) in different MBMOF concentrations (3.12, 6.25, 12.5, 25, 50, 100, 200 and 400 µg mL) were determined by direct counting after 24, 48 and 72 h. Using MTT assays, the cytotoxic impacts of the MBMOF nanocomposites on promastigotes, intracellular amastigotes, and J774 macrophages were estimated. In order to investigate their therapeutic effects, the prepared MBMOF nanocomposites (25 and 12.5 µg mL) were used as ointment three times a week to treat Leishmania major in BALB/c mice. The lesion size and weight of mice were assessed before and during the treatment. The parasitic loads were measured in spleen and liver through the culture. After 72 h, the INF-γ and IL-4 cytokines levels in the supernatant of the spleen culture were measured. To the best of the authors' knowledge, this study is the first to attempt to synthesize the bio-MOFs through an in-situ sonosynthesis route under ultrasound irradiation and examine their cytotoxicity effects on Leishmania major under in vitro and in vivo conditions.
在这项工作中，通过简单的超声化学方法合成了具有多孔层开放形态的磁性生物金属有机骨架（MBMOF）纳米复合材料，并研究了其在体外和体内条件下对利什曼原虫（MRHO/IR/75/ER）的影响。研究并优化了超声时间、试剂初始浓度和超声功率对 MBMOF 纳米复合材料尺寸和形态的影响。然后比较了纳米结构的结构信息与生物金属有机骨架晶体的结构信息。使用粉末 X 射线衍射（PXRD）、场发射扫描电子显微镜（FE-SEM）、透射电子显微镜（TEM）、傅里叶变换红外光谱（FTIR）、X 射线能谱（EDAX）、振动样品磁强计（VSM）、热重分析（TGA）和 Brunauer-Emmett-Teller（BET）技术对制备的 MBMOF 纳米复合材料进行了表征。通过直接计数，在 24、48 和 72 小时后，确定不同 MBMOF 浓度（3.12、6.25、12.5、25、50、100、200 和 400μg/mL）下的前鞭毛体（细胞/ml）的平均数量。使用 MTT 测定法评估 MBMOF 纳米复合材料对前鞭毛体、内阿米巴和 J774 巨噬细胞的细胞毒性影响。为了研究其治疗效果，将制备的 MBMOF 纳米复合材料（25 和 12.5μg/mL）作为软膏每周使用三次，以治疗 BALB/c 小鼠中的利什曼原虫。在治疗前后评估了病变大小和小鼠体重。通过培养测量脾脏和肝脏中的寄生虫负荷。72 小时后，测量脾脏培养物上清液中 INF-γ和 IL-4 细胞因子的水平。据作者所知，这项研究首次尝试通过超声辐射下的原位声合成路线合成生物 MOFs，并研究其在体外和体内条件下对利什曼原虫的细胞毒性作用。
