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生物相容性纳米多孔ZIF-8-阿拉伯树胶的合成作为姜黄素靶向递送的新型载体

Synthesis of Biocompatible Nanoporous ZIF-8-Gum Arabic as a New Carrier for the Targeted Delivery of Curcumin.

作者信息

Khalilian Seyedeh Fatemeh, Tohidi Maryam, Rastegari Banafsheh

机构信息

Department of Nanochemical Engineering, Faculty of Advanced Technologies, Shiraz University, Shiraz 71946-84636, Iran.

Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz 7143918596, Iran.

出版信息

ACS Omega. 2023 Jan 12;8(3):3245-3257. doi: 10.1021/acsomega.2c06705. eCollection 2023 Jan 24.

Abstract

The synthesis of biocompatible nanoporous zeolitic imidazolate framework-8 (ZIF-8) was performed in the presence of gum arabic (GA), curcumin (CCM), and folic acid (FA) as a template for the biomineralization process, a natural anticancer component, and a targeting agent, respectively. The synthesis of ZIF-8-GA-CCM-FA was completed in a single step at room temperature in aqueous media with a minimum amount of ethanol at a linker/metal molar ratio of 10. FA was dissolved by the alkaline medium produced by a 2-methyl imidazolium (HmIm) linker without using any toxic organic solvent or additional conjugation agents. The FA-modified carrier can target the folate receptors on Hela cells. To the best of our knowledge, this is the first report about the one-pot encapsulation of CCM and FA in a biocompatible ZIF-8-GA framework in a green solvent. This method enables high CCM loading in the ZIF-8-GA framework structure (ca. 90%) at a short time of 15 min. The effect of CCM concentration was investigated on the size, morphology, and crystallinity of the synthesized structures. The products were characterized with field emission scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, X-ray diffraction, Fourier transform infrared, and UV-vis spectroscopy techniques. The release rate of CCM from ZIF-8-GA-CCM-FA was studied at different pH values. In vitro drug release of CCM was higher in the acidic medium (pH 5.5, 6.5) compared to physiological pH (7.4). The cytotoxicity of ZIF-8-GA, ZIF-8-GA-CCM, and ZIF-8-GA-CCM-FA structures was evaluated by the standard 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the three cell lines (fibroblast (normal cell), Hela (FR-positive), and A549 (FR-negative). These results suggested that the ZIF-8-GA-CCM-FA framework can have a promising effect on the targeted treatment of cancer cells.

摘要

在阿拉伯树胶(GA)、姜黄素(CCM)和叶酸(FA)存在的情况下进行了生物相容性纳米多孔沸石咪唑酯骨架-8(ZIF-8)的合成,它们分别作为生物矿化过程的模板、天然抗癌成分和靶向剂。ZIF-8-GA-CCM-FA的合成在室温下于水性介质中以最少的乙醇一步完成,连接体/金属摩尔比为10。FA通过2-甲基咪唑鎓(HmIm)连接体产生的碱性介质溶解,无需使用任何有毒有机溶剂或额外的共轭剂。FA修饰的载体可以靶向Hela细胞上的叶酸受体。据我们所知,这是关于在绿色溶剂中将CCM和FA一锅封装到生物相容性ZIF-8-GA骨架中的首次报道。该方法能够在15分钟的短时间内使ZIF-8-GA骨架结构中CCM的负载量很高(约90%)。研究了CCM浓度对合成结构的尺寸、形态和结晶度的影响。用场发射扫描电子显微镜、布鲁诺尔-埃米特-泰勒表面积分析、X射线衍射、傅里叶变换红外光谱和紫外-可见光谱技术对产物进行了表征。研究了CCM从ZIF-8-GA-CCM-FA在不同pH值下的释放速率。与生理pH值(7.4)相比,CCM在酸性介质(pH 5.5、6.5)中的体外药物释放更高。通过标准的3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定法对三种细胞系(成纤维细胞(正常细胞)、Hela(FR阳性)和A549(FR阴性))评估了ZIF-8-GA、ZIF-8-GA-CCM和ZIF-8-GA-CCM-FA结构的细胞毒性。这些结果表明,ZIF-8-GA-CCM-FA骨架对癌细胞的靶向治疗可能有显著效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d373/9878544/5eed57753606/ao2c06705_0016.jpg

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