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牛血清白蛋白纳米球包裹的水果提取物在多种人类癌细胞系中诱导的活性氧介导的细胞凋亡

ROS-Mediated Apoptosis Induced by BSA Nanospheres Encapsulated with Fruit Extract of in Various Human Cancer Cell Lines.

作者信息

Gupta Shruti, Tejavath Kiran Kumar

机构信息

Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India.

出版信息

ACS Omega. 2021 Apr 6;6(15):10383-10395. doi: 10.1021/acsomega.1c00755. eCollection 2021 Apr 20.

Abstract

In recent decades, biodegradable polymeric nanoparticles have been used as a nanocarrier for the delivery of anticancer drugs. In the present study, we synthesize bovine serum albumin (BSA) nanospheres and evaluate their ability to incorporate a plant extract with anticancer activity. The plant extract used was the methanol fruit extract of , which is a medicinal herb. The fruit-extract-encapsulated BSA nanospheres (Cp-BSA nanospheres) were prepared using a desolvation method at various pH values of 5, 7, and 9. The nanosphere formulations were characterized using various techniques such as dynamic light scattering (DLS), ζ-potential, Fourier transform infrared spectroscopy (FTIR), and field-effect scanning electron microscopy (FESEM). The results show that the Cp-BSA nanospheres prepared at pH 7 were spherical with a uniform particle size, low polydispersity index (PDI), ζ-potential, and high entrapment efficiency (82.3%) and showed sustained release of fruit extract from Cp-BSA nanospheres in phosphate-buffered saline (PBS), pH 5. The anticancer activity was evaluated on A549, HepG2, MCF-7 cancer cell lines and HEK 293 normal cell lines. In vitro, antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, intracellular reactive oxygen species (ROS) production, and mitochondrial membrane potential were estimated. An in vitro cellular uptake study was performed using fluorescein isothiocyanate (FITC) dye at a different time of incubation, and DNA fragmentation was observed in a dose-dependent manner. The gene expression level of Bax and the suppression level of Bcl-2 were observed upon the treatment of Cp-BSA nanospheres. Thus, the Cp-BSA nanospheres triggered ROS-dependent mitochondrial apoptosis in different human cancer cell lines when compared to the noncancerous cell lines and could be used as a potential candidate for anticancer agents.

摘要

近几十年来,可生物降解的聚合物纳米颗粒已被用作抗癌药物递送的纳米载体。在本研究中,我们合成了牛血清白蛋白(BSA)纳米球,并评估了它们包载具有抗癌活性的植物提取物的能力。所使用的植物提取物是一种药草的甲醇果实提取物。采用去溶剂法在5、7和9的不同pH值下制备了包载果实提取物的BSA纳米球(Cp-BSA纳米球)。使用动态光散射(DLS)、ζ电位、傅里叶变换红外光谱(FTIR)和场效应扫描电子显微镜(FESEM)等各种技术对纳米球制剂进行了表征。结果表明,在pH 7条件下制备的Cp-BSA纳米球呈球形,粒径均匀,多分散指数(PDI)低,ζ电位低,包封率高(82.3%),并且在pH 5的磷酸盐缓冲盐水(PBS)中,Cp-BSA纳米球中的果实提取物呈现持续释放。对A549、HepG2、MCF-7癌细胞系和HEK 293正常细胞系进行了抗癌活性评估。在体外,使用2,2-二苯基-1-苦基肼(DPPH)测定法评估抗氧化活性,估算细胞内活性氧(ROS)的产生和线粒体膜电位。在不同孵育时间使用异硫氰酸荧光素(FITC)染料进行体外细胞摄取研究,并观察到剂量依赖性的DNA片段化。在处理Cp-BSA纳米球后,观察到Bax的基因表达水平和Bcl-2的抑制水平。因此,与非癌细胞系相比,Cp-BSA纳米球在不同的人类癌细胞系中触发了ROS依赖性的线粒体凋亡,可作为抗癌剂的潜在候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ef/8153748/600ae445b651/ao1c00755_0002.jpg

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