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Traditional Chinese herbal medicines are subject to heavy metal contamination. Standard detection methods are too complicated, time-consuming, and expensive for routine analysis, so low-cost methods are in high demand for rapid on-site screening. This study reports a high-sensitivity X-ray fluorescence (HS-XRF) method to determine As, Pb, and Cd residues simultaneously in herbal medicines. It couples monochromatic excitation energy dispersive X-ray fluorescence spectrometry and the fast fundamental parameters method. Each test takes only 10–30 min and costs 1/10th to 1/5th of the standard method. The detection limits, precision and accuracy were evaluated using different approaches, and application notes in practice are also proposed. This study is the first attempt to establish and evaluate HS-XRF in analyzing multiple heavy metals in herbal medicines. This rapid screening method would promote the testing efficiency and thus improve the monitoring of heavy metal contamination in herbal medicines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Multidrug resistance has been identified as a major cause of failure of cancer treatment. Due to their relative non-toxicity, selenium nanoparticles (SeNPs) have been reported as excellent cancer therapeutic nanodrugs. In this study, we designed and prepared a novel nanosystem with borneol surface-functionalized and liver targeting to overcome the multidrug resistance. Borneol (Bor)-modified SeNPs can significantly improve the stability of SeNPs and their anticancer activity. Fe(PiP)3 (PiP = 2-phenylimidazo [4,5-f][1,10] phenanthroline) is a novel anticancer agent with low solubility and stability. In this study, we have constructed a functionalized SeNPs (GAL/Bor@SeNPs) by the surface decoration of galactosamine (GAL), which is a liver targeting ligand that significantly enhanced the cellular uptake of Fe(PiP)3-loaded nanosystem via dynamin-mediated lipid raft endocytosis and clathrin-mediated endocytosis in liver cancer cells overexpressing asialoglycoprotein receptor, thus achieving amplified anticancer efficacy. This multifunctional nanosystem exhibited excellent hemocompatibility and anticancer activity comparing with Fe(PiP)3 or SeNPs alone. Remarkably, GAL/Bor@SeNPs antagonized the multidrug resistance in R-HepG2 cells by inhibiting the expression of ABC family proteins, resulting in enhanced drug accumulation and retention. Internalized nanoparticles released free iron complexes into the cytoplasm, which triggered ROS down-regulation and induced apoptosis through activating AKT and MAPKs pathways. Moreover, this nanosystem effectively prolonged the circulation time of encapsulated drugs. Taken together, this study suggests that GAL and Bor functionalization could be an effective strategy to design cancer-targeted nanomaterials to antagonize multidrug resistance in cancers. [ABSTRACT FROM AUTHOR]

The rational design and fabrication of nanodelivery systems to encapsulate drugs has been proven to be a promising and effective strategy for cancer therapy. Selenocystine (SeC), a naturally occurring selenoamino acid, has received more and more attention due to its novel pharmacological properties in the treatments of cancers. In this study, we fabricated a cancer-targeted nanodrug delivery system by encapsulating SeC into chitosan (CS) nanoparticles with folate surface decoration (FA–SeC–CSNPs) and evaluated its antiproliferative activities. The nanosystem entered the cells through endocytosis and released SeC in lysosomes under an acidic environment. Compared with SeC–CSNPs and SeC, FA–SeC–CSNPs significantly inhibited the growth of HeLa human cervical cancer cells that overexpressed folate receptors through the induction of apoptosis with the involvement of PARP cleavage and caspase activation. Moreover, FA–SeC–CSNPs also significantly suppressed the migration and invasion of HeLa cells in a dose-dependent manner. Furthermore, the intracellular nanosystem triggered the overproduction of reactive oxygen species (ROS) as early as 25 min after treatment, which activated various downstream signaling pathways such as p53, AKT and MAPKs to induce the cell death. Taken together, this study demonstrates a strategy for rational design of a cancer-targeted nanosystem loaded with selenocompounds to achieve selective cellular uptake and enhanced anticancer efficacy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The most frequent adverse effect of cisplatin-based chemotherapy is nephrotoxicity. Oxidative stress has been implicated as an important mechanism in the pathogenesis of cisplatin-induced nephrotoxicity. In the present study, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox) surface-functionalized selenium nanoparticles (Se@Trolox) with enhanced antioxidant activity have been prepared by self-assembly of trolox on the surface of the nanoparticles, and their nephroprotective effects have been investigated. Functionalization by trolox significantly enhanced cell uptake and in vitro antioxidant activities of the nanoparticles. In addition, pretreatment with Se@Trolox dose-dependently blocked cisplatin-induced cell growth inhibition against HK-2 cells. Mechanistic investigation suggested that Se@Trolox markedly prevented cisplatin-induced apoptosis in HK-2 cells, as evidenced by inhibition of chromatin condensation, DNA fragmentation, PARP cleavage and activation of caspase-3. Furthermore, Se@Trolox effectively blocked the cisplatin-induced reactive oxygen species (ROS) accumulation, activation of AKT and MAPK signaling and DNA damage-mediated p53 phosphorylation in HK-2 cells. Taken together, our findings suggest that Se@Trolox is a promising Se species with potential application in prevention of cisplatin-induced renal injury. [ABSTRACT FROM AUTHOR]

An anti-galvanic replacement reaction (AGRR) of copper(ii) ions reduced by ultra-small ssDNA-templated silver nanoclusters forming Ag–Cu alloy nanoparticles was observed. The reaction is against the classic galvanic theory and was monitored sensitively by the light-scattering technique. [ABSTRACT FROM AUTHOR]

DNA-functionalized gold nanoparticles are shown to act as a light-scattering switch. Ag+ion turns on the switch through the DNA–Au NPs conjugates based on the formation of cytosine–Ag+–cytosine base pairs, whereas cysteine turns off the light-scattering signal because it competitively binds to Ag+. [ABSTRACT FROM AUTHOR]

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.

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.

We report 3-(4,5-diphenyl-1H-imidazol-2-yl)naphthalen-2-ol (DPIN) as an interesting luminescent material displaying ESIPT with a large Stokes shift of ∼180 nm even in protic/polar solvents. Stable homo-dispersed nanoparticles formed by inter- and intramolecular H-bonds in aqueous media and the corresponding aggregation induced enhanced emission with a high quantum yield up to 0.45 were observed. Factors such as pH value and ions (cations and anions) showed a negligible effect on the fluorescence performance. A probe of 3-(4,5-diphenyl-1H-imidazol-2-yl)naphthalen-2-yl-acrylate (DPIN-A) based on this molecule was designed. The results revealed that it can be used for sensing of Cys with high selectivity and sensitivity.

Two arene Ru(II) complexes coordinated by 2-(3-methoxyphenyl)imidazole[4,5-f][1,10]phenanthroline, [(η(6)-RC6H5)Ru(m-MOPIP)Cl]Cl (R = H, ; 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 (1)H 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.

Herein we demonstrated that dinuclear zinc complexes could overcome drug resistance in R-HepG2 drug resistance hepatocellular carcinoma cells through induction of mitochondria-mediated apoptosis or by triggering mitochondria fragmentation, depletion of the membrane potential and intracellular ATP levels.

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.

In this contribution, we constructed a biosensor for screening G-quadruplex stabilizers based on the assembly of gold nanoparticles functionalized with guanine-rich (G-rich) ssDNA using a light-scattering technique. We synthesized a series of metal-terpyridine complexes and investigated their affinity for quadruplex-DNA using the biosensor. Using the ratio of intensity of the light-scattering peak (I-I 0 )/I 0 , it can intuitively present the sequence of ability of stabilizing G-quadruplex DNA as follows: complex 1 > complex 3 > MTX > complex 2 > complex 5 > complex 6 > complex 7 > complex 4 > methyl green > TO > complex 8 > cisplatin. As our method allows the quantitative analysis of stabilizer affinity, EC 50 values obtained are 4.8, 5.3, 6.1, 6.6, 6.7, 18.2, 20.2, 21.5, 32.2, 41.5 and 48.1 μM for complex 1, complex 3, MTX, complex 2, complex 5, complex 6, complex 7, complex 4, methyl green, TO and complex 8, respectively. The results have been verified by G-quadruplex fluorescent intercalator displacement (G4-FID) analysis. The proposed approach is a simple, convenient, intuitive and highly sensitive assay for screening G-quadruplex stabilizers. Our developed biosensor provides a promising tool for screening anticancer drugs.

A strategy for rapid synthesis of a chemopalette of fluorescent Ag nanoclusters based on efficient directors by only incorporating mutated bases of a C-rich ssDNA as template was proposed and used as a new fluorescence turn-on highly selective and sensitive detection method for cysteine without the interference of GSH and Hcy.

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.

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]ClO(4) (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 series of ruthenium complexes containing bis-benzimidazole derivatives have been synthesized and identified as able to target mitochondria and induce caspase-dependent apoptosis in cancer cells through superoxide overproduction.