Selenium nanoparticles (SeNPs) have attracted increasing attention due to their potential application as an effective drug delivery system. However, the conventional synthetic methods are mostly confined to solution-based synthesis that are time consuming and with low efficiency. Herein, we demonstrate the facile synthesis of highly uniform SeNPs using glucose as the reductant and surface decorator (Glu–SeNPs) that could induce cancer cell apoptosis. Glucose was used as the reducing agent to reduce sodium selenite (Na2SeO3) at high temperature (115 °C), which also acted as the surface decorator of SeNPs to prevent aggregation in an aqueous solution, thus enhancing its stability under physiological conditions. The functionalized nanoparticles demonstrated high hemocompatibility and showed selective cytotoxicity towards various human cancer cells, but not normal cells, through induction of apoptosis by initiating both intrinsic and extrinsic pathways. Furthermore, studies on the action mechanisms revealed that internalized Glu–SeNPs significantly and rapidly triggered intracellular ROS overproduction and mitochondria dysfunction to regulate the cell fate. Taken together, this study provides a new and effective method for facile synthesis of SeNPs possessing potent anticancer efficacy.

Ethnopharmacological relevanceThe roots of Actinidia eriantha Benth (AER) are commonly used traditional folk medicine for the treatment of gastric carcinoma, nasopharyngeal carcinoma, and breast carcinoma. Besides, the anti-proliferative and immunomodulatory effects of AER polysaccharides on tumor-bearing mice have been reported previously.Aim of the studyThis work was carried out to investigate the anticancer and anti-angiogenic activities of AER.Materials and methodsThe growth inhibitory effects of ethanol extracts from the leaves (EEL), stems (EES) and roots (EER) of A. eriantha on human gastric carcinoma SGC7901 cells, human nasopharyngeal carcinoma CNE2 cells, human breast carcinoma MCF7 cells and human umbilical vein endothelial cells (HUVECs) were evaluated by MTT assay. The ethyl acetate fraction from EER (EA-EER) was further investigated for the anticancer activity against SGC7901 cells and the anti-angiogenic activity in HUVECs in vitro. The apoptosis in SGC7901 cells and HUVECs was confirmed by DAPI nuclear staining and flow cytometry analysis, the effect on cellular DNA fragmentation was detected in SGC7901 cells. And the cell cycle-arresting activity in HUVECs was determined by flow cytometry. Moreover, the inhibitory effect of EA-EER on cell migration in HUVECs was observed by both wound-healing and Transwell migration assays. RT-PCR and Western-blotting were performed to determine the mRNA and protein expression levels, respectively, including Bax, Bcl-2 and caspase-3 in SGC7901 cells, as well as VEGF-A and VEGFR-2 in HUVECs. Furthermore, the in vivo anti-angiogenic activity of EA-EER was evaluated by using chick embryo chorioallantoic membrane (CAM) assay. Ultimately, the chemical components in EA-EER were isolated and purified by repeated column chromatography followed by structure characterization using 1H and 13C nuclear magnetic resonance and mass spectroscopy.ResultsCompared with EEL and EES, EER displayed the strongest growth inhibitory effect on SGC7901 cells, CNE2 cells and HUVECs. Among the EER fractions, EA-EER exhibited the most potent growth inhibitory activity against SGC7901 cells, CNE2 cells and HUVECs. Moreover, EA-EER induced obvious apoptosis in SGC7901 and HUVECs, and significantly inhibited the proliferation of HUVECs via blockade of cell cycle G1 to S progression. Furthermore, EA-EER suppressed the expression of Bcl-2 and improved the expression Bax and caspase-3 in SGC7901 cells. EA-EER not only inhibited migration of HUVECs, but also down-regulated the expression of VEGF-A and VEGFR-2 in HUVECs. In vivo, EA-EER exposure reduced the formation of blood vessels in chick embryos. A bio-guided isolation of EA-EER led to the isolation of three compounds for the first time, namely (6R, 7E, 9S)-6, 9-hydroxy-megastigman-4, 7-dien-3-one-9-O-β-D-glucopyranoside, Oleanolic acid-23-O-β-D-glucopyranoside, 3β, 23, 24-trihydroxyl-12-oleanen-28-oic acid.ConclusionThe present research demonstrated that the significant anticancer and anti-angiogenic effects of AER, providing the supportive evidence for its traditional use in the treatment for cancer. It was suggested that AER could be use as a potential source of cancer therapeutic drug.Download high-res image (302KB)Download full-size image

Selenium nanoparticles (SeNPs) have attracted increasing attention due to their potential application as an effective drug delivery system. However, the conventional synthetic methods are mostly confined to solution-based synthesis that are time consuming and with low efficiency. Herein, we demonstrate the facile synthesis of highly uniform SeNPs using glucose as the reductant and surface decorator (Glu–SeNPs) that could induce cancer cell apoptosis. Glucose was used as the reducing agent to reduce sodium selenite (Na2SeO3) at high temperature (115 °C), which also acted as the surface decorator of SeNPs to prevent aggregation in an aqueous solution, thus enhancing its stability under physiological conditions. The functionalized nanoparticles demonstrated high hemocompatibility and showed selective cytotoxicity towards various human cancer cells, but not normal cells, through induction of apoptosis by initiating both intrinsic and extrinsic pathways. Furthermore, studies on the action mechanisms revealed that internalized Glu–SeNPs significantly and rapidly triggered intracellular ROS overproduction and mitochondria dysfunction to regulate the cell fate. Taken together, this study provides a new and effective method for facile synthesis of SeNPs possessing potent anticancer efficacy.