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石墨烯氧化物/聚乙二醇/叶酸/马钱子堿纳米复合材料的合成与表征及其对 HepG2 细胞的抗癌活性。

Synthesis and Characterization of Graphene Oxide/Polyethylene Glycol/Folic Acid/Brucine Nanocomposites and Their Anticancer Activity on HepG2 Cells.

机构信息

Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura university, Makkah, Saudi Arabia.

Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan, Bangi, Selangor, Malaysia.

出版信息

Int J Nanomedicine. 2024 Feb 5;19:1109-1124. doi: 10.2147/IJN.S445206. eCollection 2024.

DOI:10.2147/IJN.S445206
PMID:38344441
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10854405/
Abstract

BACKGROUND

Liver cancer is the sixth most prevalent form of cancer and the second major cause of cancer-associated mortalities worldwide. Cancer nanotechnology has the ability to fundamentally alter cancer treatment, diagnosis, and detection.

OBJECTIVE

In this study, we explained the development of graphene oxide/polyethylene glycol/folic acid/brucine nanocomposites (GO/PEG/Bru-FA NCs) and evaluated their antimicrobial and anticancer effect on the liver cancer HepG2 cells.

METHODOLOGY

The GO/PEG/Bru-FA NCs were prepared using the co-precipitation technique and characterized using various techniques. The cytotoxicity of the GO/PEG/Bru-FA NCs was tested against both liver cancer HepG2 and non-malignant Vero cells using an MTT assay. The antimicrobial activity of the GO/PEG/Bru-FA NCs was tested against several pathogens using the well diffusion technique. The effects of GO/PEG/Bru-FA NCs on endogenous ROS accumulation, apoptosis, and MMP levels were examined using corresponding fluorescent staining assays, respectively. The apoptotic protein expressions, such as Bax, Bcl-2, and caspases, were studied using the corresponding kits.

RESULTS

The findings of various characterization assays revealed the development of GO/PEG/Bru-FA NCs with face-centered spherical morphology and an agglomerated appearance with an average size of 197.40 nm. The GO/PEG/Bru-FA NCs treatment remarkably inhibited the growth of the tested pathogens. The findings of the MTT assay evidenced that the GO/PEG/Bru-FA NCs effectively reduced the HepG2 cell growth while not showing toxicity to the Vero cells. The findings of the fluorescent assay proved that the GO/PEG/Bru-FA NCs increased ROS generation, reduced MMP levels, and promoted apoptosis in the HepG2 cells. The levels of Bax, caspase-9, and -3 were increased, and Bcl-2 was reduced in the GO/PEG/Bru-FA NCs-treated HepG2 cells.

CONCLUSION

The results of this work demonstrate that GO/PEG/Bru-FA NCs suppress viability and induce apoptosis in HepG2 cells, indicating their potential as an anticancer candidate.

摘要

背景

肝癌是全球第六大常见癌症，也是癌症相关死亡的第二大主要原因。癌症纳米技术有能力从根本上改变癌症的治疗、诊断和检测方式。

目的

本研究中，我们解释了氧化石墨烯/聚乙二醇/叶酸/马钱子碱纳米复合材料（GO/PEG/Bru-FA NCs）的开发，并评估了其对肝癌 HepG2 细胞的抗菌和抗癌作用。

方法

采用共沉淀技术制备 GO/PEG/Bru-FA NCs，并采用多种技术对其进行表征。采用 MTT 法检测 GO/PEG/Bru-FA NCs 对肝癌 HepG2 和非恶性 Vero 细胞的细胞毒性。采用平板扩散法检测 GO/PEG/Bru-FA NCs 对几种病原体的抗菌活性。采用相应的荧光染色法分别检测 GO/PEG/Bru-FA NCs 对内源性 ROS 积累、凋亡和 MMP 水平的影响。采用相应试剂盒研究 GO/PEG/Bru-FA NCs 对凋亡蛋白表达的影响，如 Bax、Bcl-2 和 caspase。

结果

各种特征分析结果表明，成功制备了具有面心立方球形形态和团聚外观的 GO/PEG/Bru-FA NCs，平均粒径为 197.40nm。GO/PEG/Bru-FA NCs 处理显著抑制了受试病原体的生长。MTT 检测结果表明，GO/PEG/Bru-FA NCs 有效抑制 HepG2 细胞生长，而对 Vero 细胞无毒性。荧光检测结果证明，GO/PEG/Bru-FA NCs 增加了 HepG2 细胞中 ROS 的产生，降低了 MMP 水平，并促进了其凋亡。GO/PEG/Bru-FA NCs 处理的 HepG2 细胞中 Bax、caspase-9 和 caspase-3 水平升高，Bcl-2 水平降低。

结论

本工作结果表明，GO/PEG/Bru-FA NCs 抑制 HepG2 细胞活力并诱导其凋亡，表明其具有作为抗癌候选物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/61122d91a12e/IJN-19-1109-g0012.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/61122d91a12e/IJN-19-1109-g0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/9918199c2e8b/IJN-19-1109-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/ac976c34c23b/IJN-19-1109-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/ea779d6022ce/IJN-19-1109-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/284f23be3ef8/IJN-19-1109-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/2b3cc9b46a69/IJN-19-1109-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/310f62afda26/IJN-19-1109-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/2375f68c67cf/IJN-19-1109-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/c141a3f0f27b/IJN-19-1109-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/80e8b5104267/IJN-19-1109-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/3cfe1916051c/IJN-19-1109-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/0cdca846b9de/IJN-19-1109-g0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ad/10854405/61122d91a12e/IJN-19-1109-g0012.jpg

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