[Show abstract][Hide abstract] ABSTRACT: Formation of T-Hg(2+)-T complexes changes the configuration of a single-stranded DNA, leading to enhanced fluorescence of an anchored cyanine-based probe that displays restricted intramolecular rotation (RIR)-induced emission. This label-free system can be used as a sensor for mercury ions with a detection limit of 4 nM.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the size-dependent penetration ability of gold nanoparticles and the potential application of ultra-small gold nanoparticle for intra-nucleus delivery and therapy. We synthesized gold nanoparticles with diameters of 2 nm, 6 nm, 10 nm and 16 nm and compared their intracellular distribution in MCF-7 breast cancer cells. Nanoparticles smaller than 10 nm (2 nm and 6 nm) could enter the nucleus while larger ones (10 nm and 16 nm) were found only in the cytoplasm. We then investigated the possibility of using ultra-small 2 nm nanoparticles as carriers for nuclear delivery of a triplex forming oligonucleotide (TFO) that binds to the c-myc promoter. Compared to free TFO, the nanoparticle-conjugated TFO was more effective at reducing c-myc RNA and c-myc protein, which resulted in reduced cell viability. Our result demonstrated the entry of gold nanoparticles into the cell nucleus is critically dependent on the size of the nanoparticles. We developed a strategy for regulating gene expression, by directly delivering triplex-forming oligonucleotides (TFOs) into the nucleus using ultra-small gold nanoparticles. More importantly, guidelines were provided to choose appropriate nanocarriers for different bio-medical purposes.
[Show abstract][Hide abstract] ABSTRACT: An efficient synthetic method for 1,8-dioxo-decahydroacridines derivatives bearing the biologically active sulfonamide moiety is described. Aromatic aldehyde reacted with 5,5-dimethyl-1,3-cyclohexanedione and sulfanilamide, with molecular iodine as catalyst, to give 1,8-dioxo-decahydroacridines derivatives in high to excellent yield. The structures of these compounds were established on the basis of elemental (C, H and N) and spectral analysis (1H NMR, 13C NMR, MS and FTIR). All the compounds were tested for their cytotoxic activity in vitro against three human tumor cell lines: human mammary cancer cells (MCF-7), human cervical carcinoma cells (Hela), and human lung cancer cells (A549) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Most of them showed moderate to potent cytotoxic activity against the tested cell lines. Among them, the most active compound 4e exhibited more efficient activity (10.92 μM) against MCF-7 cells than cisplatin (11.06 μM).
Research on Chemical Intermediates 05/2014; · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Platinum-based anti-cancer drugs such as cisplatin, oxaliplatin, and carboplatin are some of the most potent chemotherapeutic agents but have limited applications due to severe dose-limiting side effects, and a tendency for cancer cells to rapidly develop resistance. The therapeutic index can be improved through use of nanocarrier systems to target cancer cells efficiently. We developed a unique strategy to deliver Platinum(IV) drug to prostate cancer cells by constructing glutathione-stabilized (Au@GSH) gold nanoparticles. Glutathione (GSH) has well-known anti-oxidant properties, which lead to cancer regression. Here, we exploit the advantages of both the anti-oxidant properties and high surface-area-to-volume ratio of Au@GSH NPs to demonstrate their potential for delivery of Platinum(IV) drug by targeting the neuropilin-1 receptor (Nrp-1). A lethal dose of Platinum(IV) drug functionalized with the Nrp-1-targeting peptide (CRGDK) was delivered speciﬁcally to prostate cancer cells in vitro. Targeted peptide ensures specific binding to Nrp-1 receptor, leading to enhanced cellular uptake level and cell toxicity. The nanocarriers were themselves non-toxic, but exhibited high cytotoxicity and increased efficacy when functionalized with targeting peptide and drug. The uptake of drug-loaded nanocarriers is dependent on the interaction with Nrp-1 in cell lines expressing high (PC-3) and low (DU-145) levels of Nrp-1 as confirmed through inductively coupled plasma mass spectrometry (ICP-MS) and confocal microscopy. The nanocarriers have effective anti-cancer activity, through upregulation of nuclear factor kappa-B (NF-κB) protein (p50 and p65) expression and activation of NF-κB-DNA-binding activity. Our preliminary investigations with Platinum(IV) functionalized gold nanoparticles along with a targeting peptide, holds significant promise for future cancer treatment.
[Show abstract][Hide abstract] ABSTRACT: 9-Substituted berberine derivatives (4a–4f) with polyethylene glycol side chain and terminal group were synthesized and characterized by elemental (C, H, and N) and spectral analysis (NMR, HRMS and FTIR). These compounds were tested for their in vitro cytotoxic activity against four human tumor cell lines: granulocyte leukemia (HL-60), gastrocarcinoma (BGC-823), carcinoma (Bel-7402), and nasopharyngeal carcinoma (KB) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The DNA-binding properties were investigated by UV–Vis absorption, fluorescence, CD spectroscopies, and thermal denaturation measurements. The results indicated that 4a–4f exerted cytotoxic effects with selectivity against tested cell lines. 4a exhibited higher cytotoxicity than cisplatin, berberine, and berberrubine against HL-60 and BGC-823 cell lines. The length of side chains and nature of terminal groups played an important role in the cytotoxicity. Berberine derivatives binded to CT-DNA in an intercalating mode. The binding affinities decreased with the increasing length of side chains. Compounds 4a–4c and 4e could change the DNA conformation from B to A-like form.
Medicinal Chemistry Research 04/2014; 23(4). · 1.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A series of novel N-arylpyrazole derivatives, 5a–5i, were achieved from substituted phenylacetic acid via Vilsmeier–Haack reaction, hydrolysis, condensation, and aromatic substitution reaction. Their chemical structures were confirmed by 1H NMR, 13C NMR, FTIR, HRMS, and elemental analysis. The newly synthesized compounds were tested for their in vitro cytotoxic activity against Bel-7402, KB, HL-60, and BGC-823 cell lines and found to possess moderate activity.
Research on Chemical Intermediates 04/2014; · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oxidative damage is an important contributor to the morphological and the functional changes in the development of osteoporosis. In this reported work, the use of cerium oxide (CeO2) nanoparticles as a potential therapeutic agent for osteoporosis is explored. By using the primary osteoblasts (OBs) exposed to hydrogen peroxide (H2O2), it is shown that the CeO2 nanoparticles relieve the H2O2-induced oxidative damage. The protective effects of the CeO2 nanoparticles were because of a reduction in the reactive oxygen species (ROS). The level of the antioxidant enzymes was increased after treatment with the CeO2 nanoparticles in the OBs exposed to H2O2. Moreover, the cell apoptosis rate was decreased after treatment with the CeO2 nanoparticles. The CeO2 nanoparticles protect the OBs against the H2O2-induced oxidative damage, suppression of the antioxidant enzymes depletion and cell apoptosis via its ROS scavenging mechanism. The findings suggest that the CeO2 nanoparticles may have a potentially therapeutic value for the diseases related to the ROS.
[Show abstract][Hide abstract] ABSTRACT: Gold nanoparticles (AuNPs) have shown great promise for a variety of applications, including chemistry, biology, and medicine. Recently, AuNPs have found promising applications in cartilage and bone repair. However, to realize the above promised applications, more work needs to be carried out to clarify the interactions between biological systems and AuNPs. In the present study, primary osteoblasts were used to evaluate the biocompatibility of 20-nm and 40-nm AuNPs, including morphology, proliferation, differentiation, gene and protein expression, and the underlying mechanisms. The results demonstrated that AuNPs were taken up by osteoblasts and aggregated in perinuclear compartment and vescular structures, but no morphological changes were observed. AuNPs could significantly promote the proliferation of osteoblasts, enhance the ALP activities, and increase the number of bone nodules and calcium content in vitro. In addition, the expression of BMP-2, Runx-2, OCN and Col-1 was remarkably up-regulated in the presence of AuNPs. It is noteworthy that 20-nm AuNPs are more potent than 40-nm AuNPs in regulating osteoblast activities. Besides, AuNPs increased the level of ERK phosphorylation/total ERK, suggesting the activation of ERK/MAPK pathway is involved in above activities. In conclusion, AuNPs exhibited great biocompatibility with osteoblasts, and have tremendous potential to be used as drug and/or gene delivery carrier for bone and tissue engineering in the future.
Materials Science and Engineering: C. 01/2014; 42:70–77.
[Show abstract][Hide abstract] ABSTRACT: Monodisperse barium tungstate (BaWO4) hierarchical ellipsoidal particles have been prepared via a simple citrate-assisted hydrothermal method. The as-synthesized particles are non-aggregated with narrow size distribution and are composed of closely packed nanoparticles. The possible formation process of the BaWO4 ellipsoids were investigated by time-dependent experiments. During the hydrothermal process, the chelating agent trisodium citrate plays a crucial role for the formation of BaWO4 hierarchical ellipsoidal particles. The as-synthesized BaWO4:Tb3+ phosphor shows intense green emission under ultraviolet light excitation, which may find potential applications in fields of fluorescent lamps, display systems, and optoelectronic devices. Moreover, this simple synthesis route may be of great significance in the preparation of other well-defined tungstate functional materials.
Science of Advanced Materials 01/2014; 6(4). · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lanthanide-doped sodium yttrium fluoride (NaYF4) nanoparticles exhibit novel optical properties which make them be widely used in various fields. The extensive applications increase the chance of human exposure to these nanoparticles and thus raise deep concerns regarding their riskiness. In the present study, we have synthesized europium doped NaYF4 (NaYF4:Eu(3+)) nanoparticles with three diameters and used endothelial cells (ECs) as a cell model to explore the potential toxic effect. The cell viability, cytomembrane integrity, cellular uptake, intracellular localization, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis detection, caspase-3 activity and expression of inflammatory gene were studied. The results indicated that these nanoparticles could be uptaken into ECs and decrease the cell viability, induce the intracellular lactate dehydrogenase (LDH) release, increase the ROS level, and decrease the cell MMP in a size-dependent manner. Besides that, the cells were suffered to apoptosis with the caspase-3 activation, and the inflammation specific gene expressions (ICAM1 and VCAM1) were also increased. Our results suggest that the damage pathway may be related to the ROS generation and mitochondrial damage. The results provide novel evidence to elucidate their toxicity mechanisms and may be helpful for more rational applications of these compounds in the future.
Materials Science and Engineering: C. 01/2014; 43:330–342.
[Show abstract][Hide abstract] ABSTRACT: In order to evaluate the biodistribution and toxicity of europium-doped Gd2O3 nanotubes, we synthesized Gd2O3:Eu3+ nanotubes via a simple wet-chemical route at ambient pressure. The as-obtained Gd2O3:Eu3+ sample is composed of uniform and well-dispersed nanotubes. The diameters and lengths of the nanotubes are about 50 and 300 nm, respectively. All mice of the experimental groups were administered by intraperitoneal injection everyday over a period of 60 days at doses ranging from 1.25 to 125 mg/kg. Haematological and biochemical parameters and histopathology were examined, and the biodistribution of Gd element in different organs was analyzed. The results indicate that the spleen shows significant higher coefficient than the control, and other organs have no obvious difference from the control in the middle-dose and high-dose groups. There was no significant difference in the blood-elements between the control group and the experimental groups, and no significant change of all parameters can be observed in both low-dose and middle-dose groups. However, in the high-dose group, the ALT, AST, the ratio of AST/ALT, UA, LDH, and HBDH levels was increased significantly in comparison with the control group. The pathology results show that the ischemia of myocardial cell, hemorrhage of lung tissue, hepatocyte necrosis, congestion of renal interstitium, mesangial cell proliferation, and congestion of spleen sinus were induced by high-dose Gd2O3:Eu3+ nanotubes. Biodistribution experiment exhibits that Gd mainly accumulates in spleen, lung, and liver. Therefore, it can be concluded that high-dose Gd2O3:Eu3+ nanotubes were toxic, but low-dose and middle-dose groups did not show significant toxicity. The results provide novel toxicology data of Gd2O3:Eu3+ nanotubes and may be helpful for more rational applications of Gd-based compounds in the future.
Journal of Nanoparticle Research 01/2014; 16(3). · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A novel series of 4-pyrazolyl-1,8-naphthalimide derivatives have been designed and facilely synthesized. For anticancer activity in vitro, most of the compounds were found to be more toxic against human mammary cancer cells (MCF-7) than human cervical carcinoma cells (Hela) and human lung cancer cells (A549). Compounds 4i, 4h, 4b and 4a showed improved cytotoxic activity against MCF-7 cells over amonafide, in particular compounds 4i and 4h, the IC50 values of which against cell lines of MCF-7 were 0.51μM and 0.79μM, respectively. The DNA-binding properties of 4i were investigated by UV-vis, fluorescence, and Circular Dichroism (CD) spectroscopies and thermal denaturation. The results indicated that compound 4i as the DNA-intercalating agent exhibited middle binding affinity with CT-DNA.
[Show abstract][Hide abstract] ABSTRACT: A novel series of N-arylpyrazole derivatives (5a–5d, 7a–7c) has been designed and synthesized via aromatic substitution reaction of N-nonsubstituted pyrazoles with 4-fluoronitrobenzene in the presence of base. The structures of these compounds were established on the basis of elemental (C, H, and N) and spectral analysis (1H NMR, 13C NMR, HRMS, and FT-IR). All the compounds were tested for their cytotoxic activity in vitro against four human tumor cell lines: carcinoma (Bel-7402), nasopharyngeal carcinoma (KB), immature granulocyte leukemia (HL-60), and gastrocarcinoma (BGC-823) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results showed that most of the obtained compounds exhibited promising cytotoxicity against tested carcinoma cell lines with low IC50 values. The bis-pyrazole derivative 7c, bearing alkoxy group on the 5-position of phenyl ring, was the most effective one. It is inhibition of cell growth of Bel-7402 cells was 1.5-fold higher than that found for cisplatin. And, also mono-pyrazole derivatives 5a and 5b, decorated with trifluoromethyl group on the phenyl ring, displayed better cytotoxicity than that of cisplatin against Bel-7402 cell line.
Medicinal Chemistry Research 11/2013; · 1.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor cells with genetic amplifications or mutations in the fibroblast growth factor receptor (FGFR) family are often addicted to FGFR and heavily dependent on its signaling to survive. Although it is critical to understand which signaling pathway downstream of FGFR plays an essential role to guide the research and development of FGFR inhibitors, it has remained unclear partly because the tool compounds used in the literature also hit many other kinases, making the results difficult to interpret. With the development of a potent FGFR-specific inhibitor, BGJ398, we are now able to dissect various pathways with low drug concentrations to minimize multiple-target effects. Importantly, here, we show that inhibition of FGFR signaling by BGJ398 leads to only transient inhibition of ERK1/2 phosphorylation, whereas the inhibitory effect on AKT phosphorylation is sustainable, indicating that AKT, not ERK as commonly believed, serves as an appropriate pharmacodynamic biomarker for BGJ398. Although AKT inhibition by a pan-PI3K inhibitor alone has almost no effect on cell growth, heterologous expression of myr-AKT, an active form of AKT, rescues BGJ398-mediated suppression of tumor cell proliferation. These results indicate that AKT is an essential component downstream of FGFR. Finally, combination of the FGFR inhibitor BGJ398 with rapamycin significantly inhibits AKT phosphorylation and enhances their antiproliferative effects in FGFR-addicted cells, suggesting an effective combination strategy for clinical development of FGFR inhibitors.
[Show abstract][Hide abstract] ABSTRACT: Bone is one of the main target organs for the lanthanides (Ln). Biodistribution studies of Tm-based compounds in vivo showed that bone had significant uptake. But the effect of Tm(3+) on primary mouse bone marrow stromal cells (BMSCs) has not been reported. So we investigated the effect and underlying mechanisms of Tm(3+) on BMSCs. Cell viability, cell apoptosis, reactive oxygen species (ROS) level, lactate dehydrogenase (LDH) activity and mitochondrial membrane potential (MMP) were studied. The results indicated that Tm(3+) increased the viability of BMSCs at concentrations of 1 × 10(-7), 1 × 10(-6), 1 × 10(-5), and 1 × 10(-4) mol/L in a dose-dependent manner, turned to decrease the viability of BMSCs at the highest concentration of 1 × 10(-3) mol/L for 24, 48, and 72 h. Tm(3+) at 1 × 10(-3) mol/L promoted apoptosis of BMSCs, increased the ROS and LDH levels, and decreased MMP in BMSCs. Taken together, we demonstrated that Tm(3+) at 1 × 10(-3) mol/L might induce cellular apoptosis through mitochondrial pathway. These results may be helpful for more rational application of Tm-based compounds in the future.
Biological trace element research 10/2013; · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was designed to confirm the effect of the novel immunostimulators CH1b and CH2b with a thiazolidin-4-one ring on the function of macrophages. We used these two molecules to stimulate LPS-activated RAW 264.7 macrophages in vitro. After a series of essential assays, we found that CH1b and CH2b could significantly increase the production of nitric oxide (NO) by the LPS-activated RAW 264.7 macrophages, and also found that CH2b could more significantly increase the proliferation, phagocytic activity, and secretion of IL-6, IL-8 and TNF-α by LPS-activated RAW 264.7 cells more than CH1b. Furthermore, CH2b could increase the degradation of IκB-α and could promote the nuclear translocation of nuclear factor (NF)-κB p65 in LPS-activated RAW 264.7 cells. However, CH2b could also increase the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Taken together, we got that CH2b could further increase the LPS-induced activation of NF-κB and p38 MAPK in RAW 264.7 macrophages to elevate the function of macrophages, including iNOS expression, NO production, cytokines secretion, and phagocytosis.
International immunopharmacology 09/2013; · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pd(II), Cu(II) and Zn(II) complexes (1-3) based on 4'-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-2,2':6',2″-terpyridine were synthesized and characterized by UV, IR, NMR, EPR, HRMS, elemental analyses, and molar conductivity measurements. The cytotoxicity of these complexes against HL-60, BGC-823, KB, Bel-7402, A549, Hela, K562 and MCF-7 cell lines in vitro was measured by MTT method. The DNA binding property of the complexes was evaluated by UV, fluorescence, CD spectroscopies and thermal denaturation. The cytotoxicity of complexes 1 and 3 against all the tested cell lines is better than that of cisplatin. Complexes 1 and 2 exhibit 7- and 4-folds higher cytotoxicity than cisplatin against Bel-7402 cell line. Complex 3 displays the highest cytotoxicity against all the cell lines tested, and shows 7-, 14-, 8-, 11- and 8-folds higher cytotoxicity than cisplatin against Bel-7402, A549, Hela, K562 and MCF-7 cell lines. The complexes bind to DNA via intercalation mode and complex 3 stabilizes the G-quadruplex. The results reveal that all the complexes display high cytotoxicity against all the tested cancer cell lines, and complex 3 is selective for G-quadruplex over duplex DNA.
[Show abstract][Hide abstract] ABSTRACT: The response of E. coli to Hg(2+) exposure was investigated using proteomic and metalloproteomic approaches. E. coli was cultured in the LB medium containing HgCl2 and/or selenomethionine. The growth curve of E. coli was measured to estimate the toxicity of Hg(2+) or selenomethionine. After two-dimensional gel electrophoresis (2-DE), distribution of Hg in 2-DE gel was detected with synchrotron radiation X-ray fluorescence (SRXRF) at 4W1B, Beijing Synchrotron Radiation Facility. The proteins with differential expression and those containing Hg were identified with electrospray ionization tandem mass spectrometry (ESI-MS/MS) and peptide mass fingerprinting analysis. The results showed that Hg(2+) can inhibit the growth of E. coli, while supplement of selenomethionine can shorten the lag period induced by Hg(2+), indicating an antagonistic effect of selenomethionine against Hg(2+) toxicity. Mechanistically, Hg was observed to be able to bind pyruvate kinase, a glycolytic enzyme, and modulate the expression of five other proteins, including down-regulation of outer membrane protein W and up-regulation of transcription termination factor rho, cysteine synthase, transaldolase A and alkyl hydroperoxide reductase subunit C. Therefore, our results indicated that mercury may influence osmosis of plasma membrane, antioxidant defense, and glycometabolism of the microorganism. This study demonstrates the high sensitivity of SRXRF in identifying metal-associated proteins compared to conventional proteomic approaches.
[Show abstract][Hide abstract] ABSTRACT: Oxidative stress is well documented to cause injury to endothelial cells (ECs), which in turn trigger cardiovascular diseases. Previous studies revealed that cerium oxide nanoparticles (nanoceria) had antioxidant property, but the protective effect of nanoceria on ROS injury to ECs and cardiovascular diseases has not been reported. In the current study, we investigated the protective effect and underlying mechanisms of nanoceria on oxidative injury to ECs. The cell viability, lactate dehydrogenase release, cellular uptake, intracellular localization and reactive oxygen species (ROS) levels, endocytosis mechanism, cell apoptosis, and mitochondrial membrane potential were performed. The results indicated that nanoceria had no cytotoxicity on ECs but had the ability to prevent injury by H2O2. Nanoceria could be uptaken into ECs through caveolae- and clathrin-mediated endocytosis and distributed throughout the cytoplasma. The internalized nanoceria effectively attenuated ROS overproduction induced by H2O2. Apoptosis was also alleviated greatly by nanoceria pretreatment. These results may be helpful for more rational application of nanoceria in biomedical fields in the future.
Biological trace element research 06/2013; · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of cerium oxide nanoparticles on the proliferation, differentiation, and mineralization function of primary osteoblasts in vitro were evaluated. The results showed that the cell biological effects of cerium oxide nanoparticles varied with different diameters. The cytotoxicity of cerium oxide nanoparticles on primary osteoblasts varies with the size and incubation time. Sixty-nanometer cerium oxide nanoparticles show significant cytotoxicity on primary osteoblasts at 48 h exposure. Cerium oxide nanoparticles with diameters of 40 nm promoted the differentiation of osteoblasts and the promotion rate was enhanced with increasing concentration. Cerium oxide nanoparticles with diameters of 60 nm promoted the differentiation of osteoblasts at lower concentrations, but turned to inhibit the differentiation at higher concentrations. Cerium oxide nanoparticles promoted the adipogenic transdifferentiation of osteoblasts at all tested concentrations. Moreover, the effects of 60-nm cerium oxide nanoparticles were stronger than that of 40-nm cerium oxide nanoparticles. Cerium oxide nanoparticles promoted the formation of mineralized matrix nodules of osteoblasts at all tested concentrations in a dose-dependent manner and the promotion rate increased with decreasing size. The results showed that cerium oxide nanoparticles had no acute cytotoxic effects on osteoblasts and could promote the osteogenic differentiation and mineralization of osteoblasts. Moreover, the size, concentration, and culture time of nanoparticles have significant influence on the proliferation, differentiation, and mineralization of osteoblasts.
Biological trace element research 04/2013; · 1.92 Impact Factor