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N-acetylcysteine-PLGA nano-conjugate: effects on cellular toxicity and uptake of gadopentate dimeglumine.
IET Nanobiotechnology ( IF 3.8 ) Pub Date : 2020-08-06 , DOI: 10.1049/iet-nbt.2019.0374
Elham Poonaki 1 , Mohammad Esfandyar 1 , Hadi Hejazinia 1 , Seyed Esmaeil Sadat Ebrahimi 2 , Morteza Pirali Hamedani 2 , Jafar Farzaneh 1 , Mehdi Shafiee Ardestani 1
Affiliation  

Gadolinium as a contrast agent in MRI technique combined with DTPA causes contrast induced nephropathy (CIN) and nephrogenic systemic fibrosis (NSF) which can reduce by usage of antioxidants such as N-acetyl cysteine by increasing the membrane's permeability leads to lower cytotoxicity. In this study, N -acetyl cysteine-PLGA Nano-conjugate was synthesized according to stoichiometric rules of molar ratios andafter assessment by FTIR, NMR spectroscopy and Atomic Force Microscopy (AFM) imaging was combined with Magnevist® (gadopentetate dimeglumine) and its effects on the renal cells were evaluated. MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] and cellular uptake assays have indicated relatively significant toxicity of magnevist ( P < 0.05) on three cell lines including HEK293, MCF7 and L929 compared to other synthesized ligands that shown no toxicity. Moreover, systemic evaluation has shown no notable changes of blood urea nitrogen (BUN) and creatinine in kidney of mice. In consequence, antioxidant effect was increased as well as the renal toxicity of the contrast agent reduced at the cell level. As a result, PLGA-NAC nano-conjugate can be a promising choice for decreasing the magnevist toxicity for treatment and prevention of CIN and will be able to open a new horizon to research on reduction of toxicity of contrast agents by using nanoparticles.

中文翻译:

N-乙酰半胱氨酸-PLGA 纳米缀合物:对钆喷酸葡胺的细胞毒性和摄取的影响。

钆作为 MRI 技术中的造影剂与 DTPA 相结合会导致造影剂诱导的肾病 (CIN) 和肾源性系统性纤维化 (NSF),通过使用抗氧化剂(如 N-乙酰半胱氨酸)可通过增加膜的通透性来降低细胞毒性。在这项研究中,ñ -乙酰半胱氨酸-PLGA纳米缀合物根据摩尔比的化学计量规则合成,并通过FTIR、NMR光谱和原子力显微镜(AFM)成像评估后与Magnevist®(钆喷酸葡胺)相结合,评估其对肾细胞的影响. MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] 和细胞摄取试验表明 magnevist 的毒性相对显着。 < 0.05) 在包括 HEK293、MCF7 和 L929 在内的三种细胞系上,与其他没有显示毒性的合成配体相比。此外,系统评价显示小鼠肾脏的血尿素氮(BUN)和肌酐没有显着变化。结果,抗氧化作用增加并且造影剂的肾毒性在细胞水平上降低。因此,PLGA-NAC 纳米偶联物可以成为降低磁力毒性治疗和预防 CIN 的有希望的选择,并将能够为使用纳米颗粒降低造影剂毒性的研究开辟新的视野。
更新日期:2020-08-20
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