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

Rong Zhang,* Wenjuan Zhang,* Qiuhua Zhang,* Lijun Wang, Fengzhu Yang, Wenlong Sun, Zhengbao Xu, Chao Wang, Xinhua Song, Meng Wang School of Life Science and Medicine, Shandong University of Technology, Zibo, 255000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meng Wang, Email [email protected]: 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 Rikenellaceae_RC9_gut_group, Enterorhabdus and Bilophila and increased the relative abundance of Lachnospiraceae_UCG-006. Moreover, Cur/Se nanoparticle treatment significantly improved the relative abundance of Limosilactobacillus 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.Keywords: curcumin, nanodelivery system, chemotherapy, ROS, gut microbiota