Correction for ‘Microwave-assisted synthesis of polypyridyl ruthenium(II) complexes as potential tumor-targeting inhibitors against the migration and invasion of Hela cells through G2/M phase arrest’ by Jieqiong Cao et al., RSC Adv., 2017, 7, 26625–26632.

•Removal of Cu(II) from ethanol-aqueous solution by sulfur microparticles was examined.•The adsorption process could be fitted by the sigmoidal kinetic mode.•Mass transfer, coordination and physical adsorption controlled the process.•A key to further study the adsorption of the heavy metal by sulfur particles.In the present work, sulfur microparticles were produced by a facile method and employed as an adsorbent for removing copper(II) from ethanol-aqueous solution. The adsorption process attained equilibrium in 30 min and the pH was optimized at 4.5. Increasing initial metal concentration caused an increase in adsorption percentage, while increasing temperature caused a decrease. The adsorption process could be fitted by the sigmoidal kinetic model and be broken down into three stages: inducement, precipitation and equilibrium periods. The diffusion rate at the interface between solid and liquid phases determined the overall adsorption rate. Freundlich isothermal model could be used to describe the adsorption behavior. Furthermore, the XRD patterns and SEM images confirmed that the adsorption product is mainly a mixture of sulfur and CuSO4 with flower-like surface morphology. Results of this work suggest that the sulfur microparticle can be a promising adsorbent for the removal of copper ions in ethanol-aqueous solutions.Download high-res image (155KB)Download full-size image

A series of polypyridyl ruthenium(II) complexes coordinated by phenanthroimidazole derivatives [Ru(phen)2(R)](ClO4)2 (where 1 R = IP, 2 R = PIP, 3 R = p-HPIP, 4 R = p-OCH3PIP) was synthesized with an average yield of >85% under microwave irradiation at 140 °C for 30 min. The inhibitory effect of these complexes against various tumour cells were evaluated by MTT assay, and the results showed that these polypyridyl ruthenium(II) complexes exhibited acceptable inhibition against different tumour cells, especially 4, with an IC50 of 18.4 μM for Hela cells. The results showed that 4 inhibited the growth of cervical cancer Hela cells by inducing G2/M phase arrest, which was followed by slight apoptosis. Further studies showed that 4 displayed better inhibition against the invasion and metastasis of Hela cells than NAMI-A. Studies on the in vivo distribution and metabolism indicated that 4 was rapidly distributed in the entire body, absorbed by the tumour tissue and had only a small accumulation of toxicity in the body. These results demonstrated that this type of ruthenium(II) complex can block the growth of Hela cells and inhibit their migration and invasion through G2/M phase arrest, which suggests the complex could act as a potential tumour-targeting inhibitor in future clinical applications.

A synthetic method is proposed to produce nanostructures simply with diverse morphology and dimensions, which plays a critical role in the development of nanoscience and technology. Herein, a microwave-assisted approach is presented for the facile and fast synthesis of different selenium nanostructures including nanoball, nanotube and multi-armed nanorod, by reducing H2SeO3 with L-asparagine in polyethylene glycol (PEG200) for half an hour. The results showed that the diameter and morphology of selenium nanoparticles were controlled by the L-asparagine/H2SeO3 concentration ratio and the microwave irradiation time. Interestingly, morphology was changed from amorphous spherical nanoball to trigonal nanotube during the synthetic process. The morphology and chemical composition of products were characterized by spectroscopic and microscopic methods. Moreover, the DPPH and ABTS scavenging analysis of the amorphous selenium nanoball revealed that the nanoparticles with smaller diameters showed the stronger antioxidant activity. The cell viability assay showed that the amorphous selenium nanoball demonstrated low toxicity on the model cells. Our synthetic method provides a useful strategy to develop potential applications of selenium nanostructures on a large scale.

A novel selenium-containing ruthenium complex Ru(phtpy)(phenSe)Cl(ClO4) (phtpy = 4-phenyl-2,2′:6′,2′′-terpyridine, phenSe = 2-selenicimidazole[4,5-f]1,10-phenanthroline) has been synthesized and found be able to enhance radiation-induced DNA damage through superoxide overproduction, which leads to G2/M arrest and apoptosis in cancer cells by activating ROS-mediated pathways.

•A series of selenazolopyridine derivatives have been synthesized and characterized.•PSeD demonstrates novel anticancer activity.•PSeD could induce cancer cells apoptosis by scavenging intracellular ROS.A series of selenazolopyridine derivatives have been synthesized and characterized by X-ray diffraction, high resolution NMR and Mass spectrum. The in vitro anticancer activities of the synthetic compounds were screened against a panel of human cancer cell lines, human breast carcinoma MCF-7 cells, human liver carcinoma HepG2 cells and L02 normal cell line by MTT assay. By analyzing the structure–activity relationship among the synthetic compounds, it was found that 2-(phenylamino) selenazolo [5,4-b] pyridine, (PSeD, 7) had higher growth inhibitory effect on MCF-7 cells. The intracellular mechanism of cell death was evaluated by flow cytometric analysis and ROS assay, which revealed that PSeD could induce MCF-7 cells apoptosis by scavenging intracellular ROS. Taken together, we regard PSeD as an antioxidant which could inhibit cancer cell growth through induction of apoptosis.Herein we demonstrate the synthesis of selenazolopyridine derivatives and identify them as novel anticancer agents to induce cancer cells apoptosis through scavenging intracellular ROS.

Selenium nanoparticles (SeNPs) have been widely used in various biomedical applications, including cancer therapy, diagnosis and drug delivery. Herein, we fabricated a novel type of structure-transformable capsules by decoration of SeNPs with folate-chitosan to form smart-shell nanocapsules (FAC@CurP–SeNPs). The shrink particles could target cancer cells over expressing folate receptor and enter the cells via folate receptor-mediated endocytosis. FAC@CurP–SeNPs were expanded to snowflake particles under acidifying stimulus (pH 5.3), which led to enhanced drug-release over prolonged periods. Treatment with FAC@CurP–SeNPs significantly inhibited the growth of MCF-7 human breast carcinoma cells through induction of apoptosis, which was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. The contribution of extrinsic and intrinsic apoptotic pathways to the cell apoptosis was confirmed by activation of caspase-9 and caspase-8. Internalized FAC@CurP–SeNPs triggers intracellular ROS overproduction, thus activates p53, MAPKs pathways and inhibits NFκB and to promote cell apoptosis. Our results suggest that FAC@CurP–SeNPs may be a candidate for further evaluation as a agent for human cancers, and the strategy to use transformable nanocapsules could be a highly efficient way to enhance controlled drug release and anticancer efficacy.

The poor permeability of glioma parenchyma represents a major limit for antiglioblastoma drug delivery. Gracilaria lemaneiformis polysaccharide (GLP), which has a high binding affinity to αvβ3 integrin overexpressed in glioma cells, was employed in the present study to functionalize selenium nanoparticles (SeNPs) to achieve antiglioblastoma efficacy. GLP–SeNPs showed satisfactory size distribution, high stability, and selectivity between cancer and normal cells. In U87 glioma cell membrane, which has a high integrin expression level, GLP–SeNPs exhibited significantly higher cellular uptake than unmodified SeNPs. As expected, U87 cells exhibited a greater uptake of GLP–SeNPs than C6 cells with low integrin expression level. Furthermore, the internalization of GLP–SeNPs was inhibited by cyclo-(Arg-Gly-Asp-Phe-Lys) peptides, suggesting that cellular uptake into U87 cells and C6 cells occurred via αvβ3 integrin-mediated endocytosis. For U87 cells, the cytotoxicity of SeNPs decorated by GLP was enhanced significantly because of the induction of various apoptosis signaling pathways. Internalized GLP–SeNPs triggered intracellular reactive oxygen species downregulation. Therefore, p53, MAPKs, and AKT pathways were activated to advance cell apoptosis. These findings suggest that surface decoration of nanomaterials with GLP could be an efficient strategy for design and preparation of glioblastoma targeting nanodrugs.Keywords: apoptosis; cancer targeting; glioblastoma; polysaccharide; selenium nanoparticles

TrxR is an NADPH-dependent selenoenzyme upregulated in a number of cancers. It plays a pivotal role in cancer progression and represents an increasingly attractive target for anticancer drugs. The limitations of cisplatin in cancer treatment have motivated the extensive investigation to other metal complexes, especially ruthenium (Ru) complexes. In this study, we present the in vitro biological evaluation of four Ru(II) polypridyl complexes with diimine ligands, namely, [Ru(bpy)3]2+ (1), [Ru(phen)3]2+ (2), [Ru(ip)3]2+ (3), [Ru(pip)3]2+ (4) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, ip = imidazole[4,5-f][1,10]phenanthroline, pip = 2-phenylimidazo[4,5-f][1,10]phenanthroline), and demonstrate that they exhibit antiproliferative activities against A375 human melanoma cells through inhibition of TrxR. As the planarity of the structure increases, their TrxR-inhibitory effects and in vitro anticancer activities were enhanced. Among them, complex 4 exhibited higher antiproliferative activity than cisplatin, and the TrxR-inhibitory potency of 4 was more effective than auranofin, a positive TrxR inhibitor. Complex 4 suppressed the cancer cell growth through induction of apoptosis as evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Moreover, complex 4 was able to localize in mitochondria and therein induced ROS-dependent apoptosis by inhibition of TrxR activity. Activation of MAPKs, AKT, DNA damage-mediated p53 phosphorylation and inhibition of VEGFR signaling were also triggered in cells exposed to complex 4. On the basis of this evidence, we suggest that Ru polypyridyl complexes could be developed as TrxR-targeted agents that demonstrate application potentials for treatment of cancers.

The use of selenium for anticancer therapy has been heavily explored during the last decade. Amino acids (AAs) play central roles both as building blocks of proteins and intermediates in metabolism. In the present study, AAs-modified selenium nanoparticles (SeNPs@AAs) have been successfully synthesized in a simple redox system. Typical neutral (valine), acidic (aspartic acid) and basic (lysine) amino acids were used to decorate SeNPs, and the stable and homodisperse nanoparticles were characterized by zeta potential and transmission electron microscope. The result of X-ray photoelectron spectra (XPS) showed that the interaction of –NH3+ groups of the amino acids with negative-charged SeNPs could be a driving force for dispersion of the nanoparticles. The screening of in vitro anticancer activities demonstrated that SeNPs@AAs exhibited differential growth inhibitory effects on various human cancer cell lines. Among them, SeNPs decorated by Lys displayed higher anticancer efficacy than those of valine and aspartic acid. The studies on the in vitro cellular uptake mechanisms revealed that SeNPs@AAs were internalized by cancer cells through endocytosis. Flow cytometric analysis and the determination of caspase activity indicated that treatment of the MCF-7 breast adenocarcinoma cells with SeNPs@AAs led to a dose-dependent increase in apoptosis. Moreover, it was found that SeNPs@AAs-induced ROS overproduction could be the upstream signal of caspase activation and mitochondrial dysfunction in cancer cells. Taken together, our results suggest that these amino acid biocompatible nanoparticles might have potential application as chemopreventive and chemotherapeutic agents for human cancers.

Ruthenium (Ru) polypyridyl complexes have emerged as leading players among the potential metal-based candidates for cancer treatment. However, the roles of cellular translocation in their action mechanisms remain elusive. Herein we present the synthesis and characterization of a series of ruthenium (Ru) complexes containing phenanthroline derivatives with varying lipophilicities, and examine their mechanism of anticancer action. Results showed that increasing the lipophilicity of complexes can enhance the rates of cellular uptake. The in vitro anticancer efficacy of these complexes depended on the levels of ROS overproduction, rather than on cellular Ru uptake levels. The introduction of a phenolic group on the ligand effectively enhanced their intracellular ROS generation and anticancer activities. In particular, complex 4, with an ortho-phenolic group on the ligand, exhibited better selectivity between cancer and normal cells in comparison with cisplatin. Notably, complex 4 entered the cancer cells partially through transferrin receptor-mediated endocytosis, and then it translocated from lysosomes to the mitochondria, where it activated mitochondrial dysfunction by regulation of Bcl-2 family proteins, thus leading to intracellular ROS overproduction. Excess ROS amplified apoptotic signals by activating many downstream pathways such as p53 and MAPK pathways to promote cell apoptosis. Overall, this study provides a drug design strategy for discovery of Ru-based apoptosis inducers, and elucidates the intracellular translocation of these complexes.

Cisplatin-based therapy is one of the most important chemotherapy treatments for cancers. However, its efficacy is greatly limited by drug resistance and undesirable side effects. Therefore, it is of great importance to develop chemosensitizing agents to cisplatin. In the present study, we demonstrated the strategy to use methylseleninic acid (MeSe) as a synergistic agent of cisplatin and elucidated their action mechanisms. The combination of MeSe and cisplatin exhibited synergistic anticancer efficacy and achieved greater selectivity between cancer cell and normal cell. By inducing intracellular oxidative stress, MeSe potentiated cisplatin-induced DNA damage and led to enhanced p53 phosphorylation, followed by increased activation of both mitochondrial and death receptor pathway. Down-regulation of phosphorylated AKT and ERK also played important roles in the synergistic effects of MeSe and cisplatin. Our results suggested that the strategy to apply MeSe as a synergistic agent to cisplatin could be a highly efficient way to achieve anticancer synergism by targeting the intracellular redox system. MeSe might be a candidate for clinical application as a chemosensitizer to cisplatin-based therapy for cancer treatments, especially for hepatocellular carcinoma.Keywords: apoptosis; cisplatin; methylseleninic acid; ROS; synergetic effects;

Two arene Ru(II) complexes coordinated by 2-(3-methoxyphenyl)imidazole[4,5-f][1,10]phenanthroline, [(η6-RC6H5)Ru(m-MOPIP)Cl]Cl (R = H, 1; R = CH3, 2), have been prepared under microwave irradiation; the crystal structure of 2 exhibits a typical “piano stool” conformation, with bond angles for N1–Ru1–Cl1 86.02 (14)° and N2–Ru1–Cl1 84.51 (14)°. The Ru–C distance for the Ru atom bound to the benzene ring is about 0.2178(8) nm, and the average Ru–N distance for Ru atom to the two chelating N atoms is about 0.2092(4) nm. The evaluation of in vitro anticancer activities revealed that these synthetic Ru(II) complexes selectively inhibited the growth of HepG2 hepatocellular carcinoma cells, with low cytotoxicity toward LO2 human normal liver cells. The results demonstrated that the complexes exhibited great selectivity between human cancer and normal cells by comparing with the ligand m-MOPIP. Furthermore, complexes 1 and 2 could bind to c-myc G4 DNA in groove binding mode in promising affinity, and the insertion of the methyl groups in the arene ligand contributed to strengthen the binding affinity. This was also confirmed by molecular docking calculation and 1H NMR analysis which showed that both 1 and 2 can bind in the loop constructed by A6–G9 and G21–A25 base pairs in c-myc G4 DNA to block the replication of c-myc oligomer. Taken together, these results suggest that arene Ru(II) complexes display application potential as small molecule inhibitors of c-myc G4 DNA.

In the present study, two zinc(II) complexes containing bis-benzimidazole derivatives, Zn(bpbp)Cl2 (1) and [Zn(bpbp)2](ClO4)2·CH3CH2OH·H2O (2) (bpbp = 2,6-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)pyridine), have been designed, synthesized and evaluated for their in vitro anticancer activities. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. The complexes were identified as potent antiproliferative agents against a panel of five human cancer cell lines by comparing with cisplatin. Complex 2 demonstrated dose-dependent growth inhibition on MCF-7 human breast carcinoma cells with IC50 at 2.9 μM. Despite this potency, the complexes possessed great selectivity between human cancer cells and normal cells. Induction of apoptosis in MCF-7 cells by complex 2 was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Further investigation on intracellular mechanisms revealed that complex 2 was able to induce p53-dependent apoptosis in cancer cells by triggering DNA damage. On the basis of this evidence, we suggest that Zn(II) complexes containing bis-benzimidazole derivatives may be candidates for further evaluation as chemotherapeutic agents for human cancers.

Surface-capping agents play key roles in cellular uptake and biological activity of functional nanomaterials. In the present study, functionalized selenium nanoparticles (SeNPs) have been successfully synthesized using Polyporus rhinocerus water-soluble polysaccharide–protein complexes (PRW) as the capping agent during the reduction of selenium salts. The acquired monodisperse, spherical PRW-SeNPs presented desirable size distribution and stability in the solution. Moreover, PRW surface decoration significantly enhanced the cellular uptake of SeNPs via endocytosis. Exposure to PRW-SeNPs significantly inhibited the growth of A549 cells through induction of apoptosis and G2/M phase arrest (IC50 = 4.06 ± 0.25 μM) supported by an increase of sub-G1 and G2/M phase cell populations, DNA fragmentation, and chromatin condensation. Caspase-3/8 activation induced by PRW-SeNPs indicated that the activation of death receptors was the main cause of PRW-SeNP-induced apoptosis. Collectively, the results suggest that it is highly efficient to use PRW as a surface decorator of SeNPs to enhance cellular uptake and anticancer efficacy, and the PRW-SeNPs are potential chemopreventive agents for lung cancer therapy.

Surface charge plays a key role in cellular uptake and biological actions of nanomaterials. Selenium nanoparticles (SeNPs) are novel Se species with potent anticancer activity and low toxicity. This study constructed positively charged SeNPs by chitosan surface decoration to achieve selective cellular uptake and enhanced anticancer efficacy. The results of structure characterization revealed that hydroxyl groups in chitosan reacted with SeO32– ion to form special chain-shaped intermediates, which could be decomposed to form crystals upon reduction by ascorbic acid. The initial colloids nucleated and then assembled into spherical SeNPs. The positive charge of the NH3+ group on the outer surface of the nanoparticles contributed to the high stability in aqueous solutions. Moreover, a panel of four human cancer cell lines were found to be susceptible to SeNPs, with IC50 values ranging from 22.7 to 49.3 μM. Chitosan surface decoration of SeNPs significantly enhanced the selective uptake by endocytosis in cancer cells and thus amplified the anticancer efficacy. Treatment of the A375 melanoma cells with chitosan–SeNPs led to dose-dependent apoptosis, as evidenced by DNA fragmentation and phosphatidylserine translocation. Our results suggest that the use of positively charged chitosan as a surface decorator could be a simple and attractive approach to achieve selective uptake and anticancer action of nanomaterials in cancer cells.

DNA has been identified as a primary target for anticancer drug design and remains one of the most promising biological receptors for the development of chemotherapeutic agents. We have previously demonstrated that ruthenium complex [Ru(bmbp)(phen)Cl]ClO4 (RuBmP; bmbp = 2,6-bis(4-methylbenzimidazol-2-yl)pyridine) is a novel apoptosis-inducer by triggering mitochondria-mediated ROS overproduction in cancer cells. In the present work, the underlying mechanisms of the anticancer action of RuBmP were further elucidated by evaluating its DNA interaction properties and the regulating signalling pathways. Our results showed that RuBmP could effectively activate DNA strand breaks in A375 cells in a dose-dependent manner after cellular internalization. Phosphorylation of a DNA damage marker Histone H2A.X (Ser139) was thus up-regulated in treated cells. DNA damage subsequently activated p53 phosphorylation and inhibited the expression of Bcl-xL, resulting in activation of caspase-3, -8 and -9, and cleavage of poly(ADP-ribose) polymerase (PARP). The interactions between the complexes and cancer cell chromosomal and calf thymus DNA were characterized by UV–vis absorption, fluorescence intensity and viscosity measurements, which clearly demonstrated the intercalative binding of the complexes to DNA. Taken together, these results suggest that RuBmP, as a promising anticancer agent, induces cancer cell apoptosis by triggering DNA damage-mediated p53 phosphorylation.

A novel thiophene-based compound N-(4′-hydroxyphenyl)-2,5-di(2′′-thienyl)pyrrole (SNS-OH) has been synthesized and evaluated for its in vitro anticancer activities. The results showed SNS-OH effectively induced apoptosis in neuroblastoma cells through regulating the AKT and MAPK pathways.

In vitro antiproliferative effects of selenium nanoparticles (nanoSe0, 10–40 μmol/L) on HeLa (human cervical carcinoma) cells and MDA-MB-231 (human breast carcinoma) cells were examined by optical microscopic inspection and MTT assay in the present study. The nanoSe0 effectively inhibited the growth of MDA-MB-231cells and HeLa cells in a dose-dependent manner. The morphology analysis with atomic force microscope showed that the HeLa cells treated with 10 μmol/L nanoSe0 were rough and shrunken with truncated lamellipodia at terminal part of the cells. Flow cytometric analysis demonstrated that HeLa cells were arrested at S phase of the cell cycle after exposed to nanoSe0 (10 μmol/L). Taken together, our results suggested that nanoSe0 may be more helpful in cancer chemoprevention as a potential anticancer drug.Graphical abstractHighlights► Antiproliferative effects of Se nanoparticles on cancer cells were examined in vitro. ► Se nanoparticles were able to kill the HeLa and MDA-MB-231 cells. ► Se nanoparticles inhibited the growth of HeLa cells via induction of S phase arrest. ► Se nanoparticles may be as a cancer chemopreventive and chemotherapeutic agent.

A simple method for preparing 5-fluorouracil surface-functionalized selenium nanoparticles (5FU-SeNPs) with enhanced anticancer activity has been demonstrated in the present study. Spherical SeNPs were capped with 5FU through formation of Se–O and Se–N bonds and physical adsorption, leading to the stable structure of the conjugates. 5FU surface decoration significantly enhanced the cellular uptake of SeNPs through endocytosis. A panel of five human cancer cell lines was shown to be susceptible to 5FU-SeNPs, with IC50 values ranging from 6.2 to 14.4 μM. Despite this potency, 5FU-SeNP possesses great selectivity between cancer and normal cells. Induction of apoptosis in A375 human melanoma cells by 5FU-SeNPs was evidenced by accumulation of sub-G1 cell population, DNA fragmentation, and nuclear condensation. The contribution of the intrinsic apoptotic pathway to the cell apoptosis was confirmed by activation of caspase-9 and depletion of mitochondrial membrane potential. Pretreatment of cells with a general caspase inhibitor z-VAD-fmk significantly prevented 5FU-SeNP-induced apoptosis, indicating that 5FU-SeNP induced caspase-dependent apoptosis in A375 cells. Furthermore, 5FU-SeNP-induced apoptosis was found dependent on ROS generation. Our results suggest that the strategy to use SeNPs as a carrier of 5FU could be a highly efficient way to achieve anticancer synergism. 5FU-SeNPs may be a candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancers, especially melanoma.Keywords: 5-fluorouracil; apoptosis; cellular uptake; selenium nanoparticles; synergistic effects

Both selenium and allophycocyanin (APC) have been reported to show novel antioxidant activities. In this study, a fast protein liquid chromatographic method for purification of selenium-containing allophycocyanin (Se-APC) from selenium-enriched Spirulina platensis and the protective effect of Se-APC on 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress have been described. After fractionation by ammonium sulfate precipitation, and separation by DEAE-Sepharose ion-exchange and Sephacryl S-300 size exclusion chromatography, Se-APC with purity ratio (A652/A280) of 5.30 and Se concentration of 343.02 μg g–1 protein was obtained. Se-APC exhibited stronger antioxidant activity than APC by scavenging ABTS (2,2′-azinobis-3-ethylbenzothiazolin-6-sulfonic acid) and AAPH free radicals. The oxidative hemolysis and morphological changes induced by AAPH in human erythrocytes were effectively reversed by coincubation with Se-APC. Lipid oxidation induced by the pro-oxidant agent cupric chloride in human plasma, as evaluated by formation of conjugated diene, was blocked by Se-APC. The accumulation of malondialdehyde, loss of reduced glutathione, and increase in enzyme activities of glutathione peroxidase and reductase induced by AAPH in human erythrocytes were effectively suppressed by Se-APC. Furthermore, Se-APC significantly prevented AAPH-induced intracellular reactive oxygen species (ROS) generation. Taken together, our results suggest that Se-APC demonstrates application potential in treatment of diseases in which excess production of ROS acts as a casual or contributory factor.

Different crystal structure of TeO2 nanoparticles were used as the host materials to prepare the Er3+/Yb3+ ions co-doped upconversion luminescent materials. The TeO2 nanoparticles mainly kept the original morphology and phase after having been co-doped the Er3+/Yb3+ ions. All the as-prepared TeO2:Er3+/Yb3+ nanoparticles showed the green emissions (525 nm, 545 nm) and red emission (667 nm) under 980 nm excitation. The green emissions at 525 nm, 545 nm and red emission at 667 nm were attributed to the 2H11/2 → 4I15/2, 4S3/2 → 4I15/2 and 4F9/2 → 4I15/2 transitions of the Er3+ ions, respectively. For the α-TeO2:Er3+/Yb3+ (3/10 mol%) nanoparticles, three-photon process involved in the green (2H11/2 → 4I15/2) emission, while two-photon process involved in the green (4S3/2→4I15/2) and red (4F9/2 → 4I15/2) emissions. For the β-TeO2:Er3+/Yb3+ (3/10 mol%) nanoparticles, two-photon process involved in the green (2H11/2 → 4I15/2), green (4S3/2 → 4I15/2) and red (4F9/2 → 4I15/2) emissions. It suggested that the crystal structure of TeO2 nanoparticles had an effect on transition processes of the Er3+/Yb3+ ions. The emission intensities of the α-TeO2:Er3+/Yb3+ (3/10 mol%) nanoparticles and β-TeO2:Er3+/Yb3+ (3/10 mol%) nanoparticles were much stronger than those of the (α + β)-TeO2:Er3+/Yb3+ (3/10 mol%) nanoparticles.Highlights► Different crystal structure of TeO2 nanoparticles were used as the host materials to prepare TeO2:Er3+/Yb3+ nanoparticles. ► Upconversion luminescence of TeO2:Er3+/Yb3+ nanoparticles was investigated. ► The emission intensities of α (or β)-TeO2:Er3+/Yb3+ nanoparticles were stronger than those of (α + β)-TeO2:Er3+/Yb3+ nanoparticles.

A simple method for fabrication of sialic acid surface-decorated selenium nanoparticles (SA–Se–NPs) with enhanced cancer-targeting and cell-penetrating abilities has been demonstrated in the present study. Monodisperse and homogeneous spherical SA–Se–NPs with striking stability were prepared under the optimized conditions. SA surface decoration significantly increased the cellular uptake and cytotoxicity of Se–NPs in HeLa human cervical carcinoma cells. Treatments of SA–Se–NPs induced dose-dependent apoptosis in HeLa cells, as evidenced by increase in sub-G1 cell populations, nuclear condensation and formation of apoptotic bodies. Further investigation on molecular mechanisms reveals that SA–Se–NPs triggered cancer cell apoptosis through activation of caspase-3 and subsequent cleavage of PARP.Graphical abstractSialic acid surface-decorated selenium nanoparticles (SA–Se–NPs) with enhanced cancer-targeting and cell-penetrating abilities have been fabricated in the present study. SA surface decoration significantly increased the cellular uptake and cytotoxicity of Se–NPs in HeLa human cervical carcinoma cells. Treatments of SA–Se–NPs induced dose-dependent apoptosis in HeLa cells through activation of caspase-3 and subsequent cleavage of PARP.Research highlights▶ A simple method for fabrication of sialic acid surface-decorated selenium nanoparticles (SA–Se–NPs) with enhanced cancer-targeting and cell-penetrating abilities has been demonstrated. ▶ SA surface decoration significantly increased the cellular uptake and cytotoxicity of Se–NPs in HeLa human cervical carcinoma cells. ▶ SA–Se–NPs induced dose-dependent apoptosis in HeLa cells through activation of caspase-3 and subsequent cleavage of PARP.

A simple and solution-phase approach for large-scale synthesis of selenium nanoparticles (Nano-Se) by reducing sodium selenite (Na2SeO3) with l-cysteine has been demonstrated in this study. l-cysteine was used as both the reducing agent and surface modifier to control the formation of Nano-Se. The effects of reactant concentrations and ratios, and reaction time on the size and stability of Nano-Se were also investigated. The morphology and chemical composition of Nano-Se were characterized using various spectroscopic and microscopic methods. The results showed that varying the concentration ratio of l-cysteine to Na2SeO3 could control the diameter and morphology of Nano-Se, but not affecting their crystalline phases and chemical compositions. Monodisperse and homogeneous spherical Nano-Se with an average diameter of about 100 nm could be synthesized with the concentration ratio of l-cysteine to Na2SeO3 at 4:1. A striking feature of the as-synthesized Nano-Se was their good stability when dispersed in the reaction solutions, which indicates their potential in medical applications.

A series of chiral ruthenium polypyridyl complexes have been synthesized and evaluated for their in vitro anticancer activities. Λ-[Ru(bpy)2(o-tFMPIP)]Cl2 · 3H2O was identified as a novel mitochondria-targeted complex, which was able to induce mitochondria-mediated apoptosis in melanoma A375 cells through regulation of Bcl-2 family members and activation of caspases.

The preparation of tellurium dioxide (TeO2) nanoparticles in a mild condition had been studied. The acid medium, such as gallic acid or acetum was used to prepare the TeO2 nanoparticles at room temperature. The functions of acids were investigated by Nano-ZS, TEM, SEM, FTIR, Raman spectra and XRD. The results showed that the modification and modulation of gallic acid on the TeO2 nanoparticles were stronger than that of acetum. The TeO2 nanoparticles prepared in gallic acid were the orthorhombic phase β-TeO2 spheres in the range of 30–200 nm. The TeO2 nanoparticles prepared in acetum were the tetragonal phase α-TeO2 irregular flakes in the range of 40–400 nm.

A novel sulfur form, insect-like nano elemental sulfur (nano-S0) was prepared by adding cystine to sulfur-ethanol solution. The modification and modulation of cystine on elemental sulfur (S0) nanoparticles in liquid phase were studied. Transmission electron microscope (TEM), resonance Rayleigh scattering (RRS), infrared (IR) and Raman spectra (RS) were used to study the function of cystine in modification and assembly of S0 nanoparticles. The results show that the cystine modulated the S0 nanoparticles in the aspects of the size, shape and stability in the liquid phase. The cystine-nano-S0 Sol obtained was stable in solution for long time.

Chemical modulation of calcium oxalate (CaC2O4) crystals morphologies by elemental selenium nanoparticles (nanoSe0) was investigated with scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX), Fourier transform infrared spectrometry (FTIR), and X-ray diffraction (XRD) analysis. The coordination between nanoSe0 and C2O42− had great effect on the formation of CaC2O4 crystals. NanoSe0 inhibited the growth of calcium oxalate monohydrate (COM) crystals, prevented the aggregation of COM crystals and induced the formation of the spherical calcium oxalate dihydrate (COD) crystals containing selenium, which are the thermodynamically less stable phase and has a weaker affinity to the cell membranes than COM crystals. The inhibition of the crystal growth and aggregation of CaC2O4 crystals by nanoSe0 displayed concentration effects.

A series of octahedral Ru(II) polypyridyl complexes, [Ru(phen)2L]2+ (L = R-PIP and PIP = 2-phenylimidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elementary analysis, 1H NMR and ES-MS, as well as UV–visible spectra and emission spectra. The antitumor activities of these complexes and their corresponding ligands were investigated against mouse leukemia L1210 cells, human oral epidermoid carcinoma KB cells, human promyelocytic leukemia cells (HL-60) and Bel-7402 liver cancer cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. It was found that the complexes [Ru(phen)2L]2+ (L = R-PIP) exert rather potent activities against all of these cell lines, especially for the KB cells (IC50 = 4.7 ± 1.3 μM). The binding affinities of these Ru(II) complexes to CT-DNA (calf thymus DNA), as well as the DNA-unwinding properties on supercoiled pBR322 DNA were also investigated. The results showed that these Ru(II) polypyridyl complexes not only had an excellent DNA-binding property but also possessed a highly effective DNA-photocleavage ability. The structure–activity relationships and antitumor mechanism were also carefully discussed.

Selenium nanoparticle (Nano-Se) is a novel Se species with novel biological activities and low toxicity. In the present study, we demonstrated a simple method for synthesis of size-controlled Nano-Se by adding Undaria pinnatifida polysaccharides to the redox system of selenite and ascorbic acid. A panel of four human cancer cell lines was shown to be susceptible to Nano-Se, with IC50 values ranging from 3.0 to 14.1 μM. Treatment of A375 human melanoma cells with the Nano-Se resulted in dose-dependent cell apoptosis as indicated by DNA fragmentation and phosphatidylserine translocation. Further investigation on intracellular mechanisms found that Nano-Se treatment triggered apoptotic cell death in A375 cells with the involvement of oxidative stress and mitochondrial dysfunction. Our results suggest that Nano-Se may be a candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancers, especially melanoma cancer.

DNA has been identified as a primary target for anticancer drug design and remains one of the most promising biological receptors for the development of chemotherapeutic agents. We have previously demonstrated that ruthenium complex [Ru(bmbp)(phen)Cl]ClO4 (RuBmP; bmbp = 2,6-bis(4-methylbenzimidazol-2-yl)pyridine) is a novel apoptosis-inducer by triggering mitochondria-mediated ROS overproduction in cancer cells. In the present work, the underlying mechanisms of the anticancer action of RuBmP were further elucidated by evaluating its DNA interaction properties and the regulating signalling pathways. Our results showed that RuBmP could effectively activate DNA strand breaks in A375 cells in a dose-dependent manner after cellular internalization. Phosphorylation of a DNA damage marker Histone H2A.X (Ser139) was thus up-regulated in treated cells. DNA damage subsequently activated p53 phosphorylation and inhibited the expression of Bcl-xL, resulting in activation of caspase-3, -8 and -9, and cleavage of poly(ADP-ribose) polymerase (PARP). The interactions between the complexes and cancer cell chromosomal and calf thymus DNA were characterized by UV–vis absorption, fluorescence intensity and viscosity measurements, which clearly demonstrated the intercalative binding of the complexes to DNA. Taken together, these results suggest that RuBmP, as a promising anticancer agent, induces cancer cell apoptosis by triggering DNA damage-mediated p53 phosphorylation.

Two arene Ru(II) complexes coordinated by 2-(3-methoxyphenyl)imidazole[4,5-f][1,10]phenanthroline, [(η6-RC6H5)Ru(m-MOPIP)Cl]Cl (R = H, 1; R = CH3, 2), have been prepared under microwave irradiation; the crystal structure of 2 exhibits a typical “piano stool” conformation, with bond angles for N1–Ru1–Cl1 86.02 (14)° and N2–Ru1–Cl1 84.51 (14)°. The Ru–C distance for the Ru atom bound to the benzene ring is about 0.2178(8) nm, and the average Ru–N distance for Ru atom to the two chelating N atoms is about 0.2092(4) nm. The evaluation of in vitro anticancer activities revealed that these synthetic Ru(II) complexes selectively inhibited the growth of HepG2 hepatocellular carcinoma cells, with low cytotoxicity toward LO2 human normal liver cells. The results demonstrated that the complexes exhibited great selectivity between human cancer and normal cells by comparing with the ligand m-MOPIP. Furthermore, complexes 1 and 2 could bind to c-myc G4 DNA in groove binding mode in promising affinity, and the insertion of the methyl groups in the arene ligand contributed to strengthen the binding affinity. This was also confirmed by molecular docking calculation and 1H NMR analysis which showed that both 1 and 2 can bind in the loop constructed by A6–G9 and G21–A25 base pairs in c-myc G4 DNA to block the replication of c-myc oligomer. Taken together, these results suggest that arene Ru(II) complexes display application potential as small molecule inhibitors of c-myc G4 DNA.

A novel selenium-containing ruthenium complex Ru(phtpy)(phenSe)Cl(ClO4) (phtpy = 4-phenyl-2,2′:6′,2′′-terpyridine, phenSe = 2-selenicimidazole[4,5-f]1,10-phenanthroline) has been synthesized and found be able to enhance radiation-induced DNA damage through superoxide overproduction, which leads to G2/M arrest and apoptosis in cancer cells by activating ROS-mediated pathways.

The use of selenium for anticancer therapy has been heavily explored during the last decade. Amino acids (AAs) play central roles both as building blocks of proteins and intermediates in metabolism. In the present study, AAs-modified selenium nanoparticles (SeNPs@AAs) have been successfully synthesized in a simple redox system. Typical neutral (valine), acidic (aspartic acid) and basic (lysine) amino acids were used to decorate SeNPs, and the stable and homodisperse nanoparticles were characterized by zeta potential and transmission electron microscope. The result of X-ray photoelectron spectra (XPS) showed that the interaction of –NH3+ groups of the amino acids with negative-charged SeNPs could be a driving force for dispersion of the nanoparticles. The screening of in vitro anticancer activities demonstrated that SeNPs@AAs exhibited differential growth inhibitory effects on various human cancer cell lines. Among them, SeNPs decorated by Lys displayed higher anticancer efficacy than those of valine and aspartic acid. The studies on the in vitro cellular uptake mechanisms revealed that SeNPs@AAs were internalized by cancer cells through endocytosis. Flow cytometric analysis and the determination of caspase activity indicated that treatment of the MCF-7 breast adenocarcinoma cells with SeNPs@AAs led to a dose-dependent increase in apoptosis. Moreover, it was found that SeNPs@AAs-induced ROS overproduction could be the upstream signal of caspase activation and mitochondrial dysfunction in cancer cells. Taken together, our results suggest that these amino acid biocompatible nanoparticles might have potential application as chemopreventive and chemotherapeutic agents for human cancers.

Ruthenium (Ru) polypyridyl complexes have emerged as leading players among the potential metal-based candidates for cancer treatment. However, the roles of cellular translocation in their action mechanisms remain elusive. Herein we present the synthesis and characterization of a series of ruthenium (Ru) complexes containing phenanthroline derivatives with varying lipophilicities, and examine their mechanism of anticancer action. Results showed that increasing the lipophilicity of complexes can enhance the rates of cellular uptake. The in vitro anticancer efficacy of these complexes depended on the levels of ROS overproduction, rather than on cellular Ru uptake levels. The introduction of a phenolic group on the ligand effectively enhanced their intracellular ROS generation and anticancer activities. In particular, complex 4, with an ortho-phenolic group on the ligand, exhibited better selectivity between cancer and normal cells in comparison with cisplatin. Notably, complex 4 entered the cancer cells partially through transferrin receptor-mediated endocytosis, and then it translocated from lysosomes to the mitochondria, where it activated mitochondrial dysfunction by regulation of Bcl-2 family proteins, thus leading to intracellular ROS overproduction. Excess ROS amplified apoptotic signals by activating many downstream pathways such as p53 and MAPK pathways to promote cell apoptosis. Overall, this study provides a drug design strategy for discovery of Ru-based apoptosis inducers, and elucidates the intracellular translocation of these complexes.

In the present study, two zinc(II) complexes containing bis-benzimidazole derivatives, Zn(bpbp)Cl2 (1) and [Zn(bpbp)2](ClO4)2·CH3CH2OH·H2O (2) (bpbp = 2,6-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)pyridine), have been designed, synthesized and evaluated for their in vitro anticancer activities. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. The complexes were identified as potent antiproliferative agents against a panel of five human cancer cell lines by comparing with cisplatin. Complex 2 demonstrated dose-dependent growth inhibition on MCF-7 human breast carcinoma cells with IC50 at 2.9 μM. Despite this potency, the complexes possessed great selectivity between human cancer cells and normal cells. Induction of apoptosis in MCF-7 cells by complex 2 was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Further investigation on intracellular mechanisms revealed that complex 2 was able to induce p53-dependent apoptosis in cancer cells by triggering DNA damage. On the basis of this evidence, we suggest that Zn(II) complexes containing bis-benzimidazole derivatives may be candidates for further evaluation as chemotherapeutic agents for human cancers.

Selenium nanoparticles (SeNPs) have been widely used in various biomedical applications, including cancer therapy, diagnosis and drug delivery. Herein, we fabricated a novel type of structure-transformable capsules by decoration of SeNPs with folate-chitosan to form smart-shell nanocapsules (FAC@CurP–SeNPs). The shrink particles could target cancer cells over expressing folate receptor and enter the cells via folate receptor-mediated endocytosis. FAC@CurP–SeNPs were expanded to snowflake particles under acidifying stimulus (pH 5.3), which led to enhanced drug-release over prolonged periods. Treatment with FAC@CurP–SeNPs significantly inhibited the growth of MCF-7 human breast carcinoma cells through induction of apoptosis, which was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. The contribution of extrinsic and intrinsic apoptotic pathways to the cell apoptosis was confirmed by activation of caspase-9 and caspase-8. Internalized FAC@CurP–SeNPs triggers intracellular ROS overproduction, thus activates p53, MAPKs pathways and inhibits NFκB and to promote cell apoptosis. Our results suggest that FAC@CurP–SeNPs may be a candidate for further evaluation as a agent for human cancers, and the strategy to use transformable nanocapsules could be a highly efficient way to enhance controlled drug release and anticancer efficacy.