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姜黄素修饰的硒纳米颗粒通过调节肠道微生物群和化疗改善小鼠S180肿瘤治疗效果。

Curcumin-Modified Selenium Nanoparticles Improve S180 Tumour Therapy in Mice by Regulating the Gut Microbiota and Chemotherapy.

作者信息

Zhang Rong, Zhang Wenjuan, Zhang Qiuhua, Wang Lijun, Yang Fengzhu, Sun Wenlong, Xu Zhengbao, Wang Chao, Song Xinhua, Wang Meng

机构信息

School of Life Science and Medicine, Shandong University of Technology, Zibo, 255000, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Dec 20;19:13653-13669. doi: 10.2147/IJN.S476686. eCollection 2024.

DOI:10.2147/IJN.S476686
PMID:39720218
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11668068/
Abstract

PURPOSE

This study aimed to synthesize curcumin-modified selenium (Cur/Se) nanoparticles via a simple and green method for tumour treatment and explore their effects on the gut microbiota.

METHODS

Curcumin was applied as a reducing and capping agent for the construction of Cur/Se nanoparticles with Tween 80 as a stabilizer. The drug release behaviour and DPPH and ABTS radical scavenging activities of the Cur/Se nanoparticles were detected. MTT and CCK8 assays were used to evaluate the cytotoxicity against HeLa and S180 tumour cells. The cellular distribution, uptake and reactive oxygen species (ROS) levels were detected. In vivo anti-S180 tumour activity was studied by oral administration. 16S rRNA Illumina high-throughput sequencing technology was used to analyse the gut microbiota in ileocecal faeces.

RESULTS

Nanoparticles with good water dispersibility and a size of 6.86 nm were obtained. The characteristic peaks of curcumin were observed in the UV and FTIR spectra of the Cur/Se nanoparticles. Curcumin release from the Cur/Se nanoparticles occurred in a pH-dependent and sustained manner at 48 h. The Cur/Se nanoparticles presented significantly higher DPPH and ABTS radical scavenging rates than the same concentration of free curcumin. At 48 h, the Cur/Se nanoparticles showed higher cytotoxicity against HeLa and S180 tumour cells. The results of the cellular uptake experiments revealed that the Cur/Se nanoparticles significantly delivered more curcumin into the HeLa tumour cells and induced greater ROS production. In vivo, the Cur/Se nanoparticles significantly inhibited S180 tumours, with a 54.33% tumour inhibitory rate. Cur and Cur/Se nanoparticles significantly reduced the relative abundances of and and increased the relative abundance of . Moreover, Cur/Se nanoparticle treatment significantly improved the relative abundance of compared with that in the curcumin group.

CONCLUSION

Cur/Se nanoparticles could increase the bioactivity of curcumin and improve cancer therapy by regulating the gut microbiota.

摘要

目的

本研究旨在通过一种简单绿色的方法合成姜黄素修饰的硒(Cur/Se)纳米粒子用于肿瘤治疗,并探索其对肠道微生物群的影响。

方法

以姜黄素作为还原剂和封端剂,吐温80作为稳定剂构建Cur/Se纳米粒子。检测Cur/Se纳米粒子的药物释放行为以及对DPPH和ABTS自由基的清除活性。采用MTT和CCK8法评估对HeLa和S180肿瘤细胞的细胞毒性。检测细胞内分布、摄取及活性氧(ROS)水平。通过口服给药研究体内抗S180肿瘤活性。利用16S rRNA Illumina高通量测序技术分析回盲部粪便中的肠道微生物群。

结果

获得了具有良好水分散性、尺寸为6.86 nm的纳米粒子。在Cur/Se纳米粒子的紫外和傅里叶变换红外光谱中观察到了姜黄素的特征峰。Cur/Se纳米粒子在48小时时姜黄素的释放呈pH依赖性且具有缓释特性。Cur/Se纳米粒子对DPPH和ABTS自由基的清除率明显高于相同浓度的游离姜黄素。在48小时时,Cur/Se纳米粒子对HeLa和S180肿瘤细胞显示出更高的细胞毒性。细胞摄取实验结果表明,Cur/Se纳米粒子能显著将更多姜黄素递送至HeLa肿瘤细胞并诱导产生更多的ROS。在体内,Cur/Se纳米粒子显著抑制S180肿瘤,肿瘤抑制率为54.33%。Cur和Cur/Se纳米粒子显著降低了[具体菌种1]和[具体菌种2]的相对丰度,并增加了[具体菌种3]的相对丰度。此外,与姜黄素组相比,Cur/Se纳米粒子处理显著提高了[具体菌种4]的相对丰度。

结论

Cur/Se纳米粒子可提高姜黄素的生物活性,并通过调节肠道微生物群改善癌症治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b17/11668068/546c52b58366/IJN-19-13653-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b17/11668068/2755c5bfd7c6/IJN-19-13653-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b17/11668068/dfedece62da4/IJN-19-13653-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b17/11668068/ca0372a95970/IJN-19-13653-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b17/11668068/cd8106e140db/IJN-19-13653-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b17/11668068/cca40b6effed/IJN-19-13653-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b17/11668068/a195eb6553b8/IJN-19-13653-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b17/11668068/149796c59b70/IJN-19-13653-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b17/11668068/546c52b58366/IJN-19-13653-g0008.jpg

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