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氮掺杂石墨烯包覆的混合氧化铁纳米颗粒对肝癌细胞HepG2的选择性细胞毒性作用作为一种新的潜在治疗方法。

Selective cytotoxic effects of nitrogen-doped graphene coated mixed iron oxide nanoparticles on HepG2 as a new potential therapeutic approach.

作者信息

Demir Zeynep, Sungur Berkay, Bayram Edip, Özkan Aysun

机构信息

Department of Biology, Institute of Natural and Applied Sciences, Akdeniz University, 07070, Antalya, Turkey.

Department of Chemistry, Institute of Natural and Applied Sciences, Akdeniz University, 07070, Antalya, Turkey.

出版信息

Discov Nano. 2024 Feb 22;19(1):33. doi: 10.1186/s11671-024-03977-y.

DOI:10.1186/s11671-024-03977-y
PMID:38386123
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10884380/
Abstract

New selective therapeutics are needed for the treatment of hepatocellular carcinoma (HCC), the 7th most common cancer. In this study, we compared the cytotoxic effect induced by the release of pH-dependent iron nanoparticles from nitrogen-doped graphene-coated mixed iron oxide nanoparticles (FeO/N-GN) with the cytotoxic effect of nitrogen-doped graphene (N-GN) and commercial graphene nanoflakes (GN) in Hepatoma G2 (HepG2) cells and healthy cells. The cytotoxic effect of nanocomposites (2.5-100 ug/ml) on HepG2 and healthy fibroblast (BJ) cells (12-48 h) was measured by Cell Viability assay, and the half maximal inhibitory concentration (IC) was calculated. After the shortest (12 h) and longest incubation (48 h) incubation periods in HepG2 cells, IC values of FeO/N-GN were calculated as 21.95 to 2.11 µg.mL, IC values of N-GN were calculated as 39.64 to 26.47 µg.mL and IC values of GN were calculated as 49.94 to 29.94, respectively. After 48 h, FeO/N-GN showed a selectivity index (SI) of 10.80 for HepG2/BJ cells, exceeding the SI of N-GN (1.27) by about 8.5-fold. The high cytotoxicity of FexOy/N-GN was caused by the fact that liver cancer cells have many transferrin receptors and time-dependent pH changes in their microenvironment increase iron release. This indicates the potential of FeO/N-GN as a new selective therapeutic.

摘要

肝细胞癌（HCC）是第七大常见癌症，治疗该疾病需要新的选择性疗法。在本研究中，我们比较了氮掺杂石墨烯包覆的混合氧化铁纳米颗粒（FeO/N-GN）释放pH依赖性铁纳米颗粒所诱导的细胞毒性效应，以及氮掺杂石墨烯（N-GN）和商业石墨烯纳米片（GN）对肝癌G2（HepG2）细胞和健康细胞的细胞毒性效应。通过细胞活力测定法测量纳米复合材料（2.5 - 100微克/毫升）对HepG2和健康成纤维细胞（BJ）细胞（12 - 48小时）的细胞毒性效应，并计算半数最大抑制浓度（IC）。在HepG2细胞中最短（12小时）和最长孵育期（48小时）后，FeO/N-GN的IC值计算为21.95至2.11微克/毫升，N-GN的IC值计算为39.64至26.47微克/毫升，GN的IC值计算为49.94至29.94微克/毫升。48小时后，FeO/N-GN对HepG2/BJ细胞的选择性指数（SI）为10.80，比N-GN的SI（1.27）高出约8.5倍。FexOy/N-GN的高细胞毒性是由于肝癌细胞有许多转铁蛋白受体，且其微环境中随时间变化的pH值增加了铁的释放。这表明FeO/N-GN作为一种新的选择性疗法具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/0dfea5a3a890/11671_2024_3977_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/cfd8d1919daa/11671_2024_3977_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/e60f1b754eaa/11671_2024_3977_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/9ee153183cad/11671_2024_3977_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/250f0fbb99a1/11671_2024_3977_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/293b1cb21795/11671_2024_3977_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/ef23d2350de2/11671_2024_3977_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/0dfea5a3a890/11671_2024_3977_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/cfd8d1919daa/11671_2024_3977_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/e60f1b754eaa/11671_2024_3977_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/9ee153183cad/11671_2024_3977_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/250f0fbb99a1/11671_2024_3977_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/293b1cb21795/11671_2024_3977_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/ef23d2350de2/11671_2024_3977_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/902a/10884380/0dfea5a3a890/11671_2024_3977_Fig7_HTML.jpg

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[3]
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[4]
Ultrasmall iron oxide nanoparticles cause significant toxicity by specifically inducing acute oxidative stress to multiple organs.

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[5]
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Superparamagnetic Iron Oxide Nanoparticles: Cytotoxicity, Metabolism, and Cellular Behavior in Biomedicine Applications.

Int J Nanomedicine. 2021

[7]
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