[Show abstract][Hide abstract] ABSTRACT: Small-molecule ligands for stabilizing the G-quadruplex in telomeres are promising chemotherapeutic agents. Despite extensive research, few G-quadruplex-stabilizing ligands have been clinically approved to date. We hypothesized that metal ions may be able to interfere with the ligand-mediated stabilization of the G-quadruplex. Here we found that several metal ions could interfere with the Na(+)-induced G-quadruplex conformation even in the presence of a ligand. The destabilizing effects of metal ions may not be negligible as most of them are essential elements in organisms. In contrast, Ba(2+) was found to be a potent stabilizing cation, which could compete with other destabilizing cations to modulate the stability of the G-quadruplex. Moreover, the destabilizing effects of divalent or trivalent cations were considerably inhibited when a metal chelator was used. These data suggested that the unfavorable effects of destabilizing cations must be minimized for enhancing the ligand-mediated stabilization of the G-quadruplex.
[Show abstract][Hide abstract] ABSTRACT: In this study, Cu(II)-mediated differential alteration of cysteine (Cys) reactivity is reported by using a Cys-specific fluorescent probe. The probe could react with Cys to give out strong fluorescence. When Cys was preincubated with Cu(II), the fluorescence of the probe was decreased due to the inhibition of Cys's reactivity by Cu(II). Remarkably, experimental results reveal that the probe could detect Cu(II) at subnanomolar concentrations. In contrast, Cu(II) could only partially inhibit the reaction between Cys and Ellman's reagent (DTNB). Furthermore, selectivity experiments show that Cu(II) is a much more potent inhibitor for Cys compared to other metal ions. Cell imaging experiments also confirm the inhibitory effects of Cu(II) on Cys's reactivity in living cells. We envision that the probe could add a useful tool for sensitive and selective detection of Cu(II) for biomedical research.
[Show abstract][Hide abstract] ABSTRACT: The effects of cerium oxide nanoparticles (nanoceria) on the proliferation, osteogenic and adipogenic differentiation of primary mouse bone marrow stromal cells (BMSCs) were studied by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), alkaline phosphatase
(ALP) activity, collagen production, alizarin red-S (ARS) and oil red o stain assays. The results indicated that nanoceria increased the viability of BMSCs at all tested concentrations with evident dose dependence for 24 and 72 h. On day 14, nanoceria inhibited the osteogenic differentiation
of BMSCs at all tested concentrations. On day 19 and 24, nanoceria inhibited the formation of mineralized matrix nodules of BMSCs at all tested concentrations. On day 17, nanoceria inhibited the adipogenic differentiation of BMSCs at all tested concentrations. This suggests that the effects
of nanoceria on the proliferation, osteogenic differentiation and adipogenic differentiation of BMSCs are very complicated. Both the concentration and culture time have significant influence on the proliferation, osteogenic differentiation and adipogenic differentiation of BMSCs. These results
will be helpful for rational applications of nanoceria in the future.
Journal of Nanoscience and Nanotechnology 09/2015; 15(9):6444-6451. DOI:10.1166/jnn.2015.10709 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Potential bioaccumulation is one of the biggest limitations for silica nano drug delivery system in cancer therapy. In this study, mesoporous silica nanoparticles/hydroxylapatite (MSNs/HAP) hybrid drug carrier, which enhanced the biodegradability of silica, was developed by a one-step method. The morphology and structure of the nanoparticles were characterized by TEM, DLS, FT-IR, XRD, N2 adsorption-desorption isotherms, XPS, and the drug loading and release behaviors were tested. TEM and ICP-OES results indicate that the degradability of the nanoparticles has been significantly improved by Ca2+ flee from the skeleton in acid environment. The MSNs/HAP sample exhibits higher drug loading content as about five times as that of MSNs. The biological experiment results show that the MSNs/HAP not only exhibits good biocompatibility and antitumor effect, but also greatly reduces the side effects of free DOX. The as-synthesized hybrid nanoparticles may act as a promising drug delivery system due to their good biocompatibility, high drug loading efficiency, pH sensitivity, and excellent biodegradability.
[Show abstract][Hide abstract] ABSTRACT: To better understand the potential impact of Eu3+ doped gadolinium oxide nanotubes (Gd2O3:Eu3+ nanotubes) on human health, we investigated their biodistribution, subacute toxicity, and hepatic injury in mice under different dosages (4.0, 40.0, and 400.0 mg kg-1). The results showed that the gadolinium element was mainly accumulated in the spleen, liver, lung, kidney, and bone. The relative organ weight of spleen in the middle-dose group and high-dose group was significant higher than that of the control group. However, the relative organ weight of liver and kidney had no obvious difference from the control group. Besides, the change of toxicity on the hematological system was not noticeable under the tested doses. The high-dose Gd2O3:Eu3+ nanotubes increased the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels, but no significant difference was observed in the low-dose group and middle-dose group compared with the control group. These changes demonstrated that high-dose Gd2O3:Eu3+ nanotubes induced liver injury. Based on the changes of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), glutathione S-transferase (GST), reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonylation levels, it can be deduced that high-dose Gd2O3:Eu3+ nanotubes could induce liver injury by oxidative stress. Furthermore, the levels of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-8 (IL-8), increased upon high-dose Gd2O3:Eu3+ nanotube treatment. The results may benefit the applications of Gd2O3:Eu3+ nanotubes. This journal is
[Show abstract][Hide abstract] ABSTRACT: To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG-Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX-sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp-DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with reduced toxicity. These results suggested that this site-specific drug-releasing system could be exploited as a promising treatment for cancers with repeated administration.
[Show abstract][Hide abstract] ABSTRACT: Uniform and well-dispersed walnut kernel-like mesoporous silica nanoparticles (MSNs) with diameters about 100 nm have been synthesized by a templating sol-gel route. After an annealing process, the as-obtained sample (DLMSNs) inherits the well-defined morphology and good dispersion of MSNs, and exhibits bright white-blue luminescence, higher specific surface area and pore volume, and better biocompatibility. The drug loading and release profiles show that DLMSNs have high drug loading capacity, and exhibit an initial burst release followed by a slow sustained release process. Interestingly, the luminescence intensity of the DLMSNs-DOX system increases gradually with the increase of cumulative released DOX, which can be verified by the confocal laser scanning images. The drug carrier DLMSNs can potentially be applied as a luminescent probe for monitoring the drug release process. Moreover, the DLMSNs-DOX system exhibits potent anticancer effect against three kinds of cancer cells (HeLa, MCF-7, and A549 cells).
[Show abstract][Hide abstract] ABSTRACT: One of the main target organs for the lanthanides (Ln) is bone. Previous studies revealed that ytterbium (Yb) produced damage to the skeletal system in vivo. But the effects of Yb3+ on bone marrow stromal cells (BMSCs) in vitro had not been reported. In this paper, cell viability, apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and lactate dehydrogenase (LDH) were measured in order to study the effects of Yb3+ on BMSCs. The results indicated that Yb3+ displayed a slight positive effect on the BMSCs viability at concentrations of 1×10−6, 1×10−5, and 1×10−4 mol/L, but turned to decrease the viability of BMSCs at the highest concentration of 1×10−3 mol/L for 24, 48 and 72 h. Yb3+ at 1×10−3 mol/L promoted apoptosis of BMSCs, increased the levels of ROS and LDH, and decreased MMP in BMSCs. It suggested that the precipitate of YbPO4 might decrease the viability of BMSCs. Yb3+ induced the apoptosis of BMSCs via mitochondrial pathway. The results might be useful for more rational application of Yb-based compounds in the future.
[Show abstract][Hide abstract] ABSTRACT: As an intensely studied computed tomography (CT) contrast agent, gold nanoparticle has been suggested to be combined with fluorescence imaging modality to offset the low sensitivity of CT. However, the strong quenching of gold nanoparticle on fluorescent dyes requires complicated design and shielding to overcome. Herein, we report a unique nanoprobe (M-NPAPF-Au) co-loading an aggregation-induced emission (AIE) red dye and gold nanoparticles into DSPE-PEG2000 micelles for dual-modal fluorescence/CT imaging. The nanoprobe was prepared based on a facile method of “one-pot ultrasonic emulsification”. Surprisingly, in the micelles system, fluorescence dye (NPAPF) efficiently overcame the strong fluorescence quenching of shielding-free gold nanoparticles and retained the crucial AIE feature. In vivo studies demonstrated the nanoprobe had superior tumor-targeting ability, excellent fluorescence and CT imaging effects. The totality of present studies clearly indicates the significant potential application of M-NPAPF-Au as a dual-modal non-invasive fluorescence/X-ray CT nanoprobe for in vivo tumor-targeted imaging and diagnosis.
[Show abstract][Hide abstract] ABSTRACT: It has been well-established that nanomaterials provide a robust framework into which two or more functional moieties can be integrated to offer multifunctional and synergetic applications. We report here the facile synthesis and systematical investigation of the luminomagnetic core–shell nanoparticles (NPs) with the magnetic Fe3O4 core coated with a silica shell incorporating fluorescent [Ru(bpy)3]2 +. The luminomagnetic NPs were monodisperse and spherical in shape with a diameter of 60 ± 10 nm. The luminomagnetic NPs possessed not only the desirable optical signature of Ru(bpy)32 + but also the distinctive magnetic profile of Fe3O4, where a strong red-orange emission and the super-paramagnetic characteristics with the saturation magnetization values ca. 10 emu/g were observed for the luminomagnetic NPs. As revealed by Alamar blue assay and flow cytometry analysis, the Fe3O4 NPs decrease the cell viability of HepG2 by ca. 10%, while an increase by ca. 10% on HepG2 cell proliferation was revealed after the silica shell was coated onto Fe3O4 NPs, suggesting that the silica shell serves as a protective layer to increase the biocompatibility of the luminomagnetic NPs. Confocal laser scanning microscopy, transition electron microscopy and magnetic resonance (MR) images confirmed that the luminomagnetic NPs can enter into the interiors of HepG2 cells without damage, highlighting their capabilities for simultaneous optical fluorescence imaging and T2 MR imaging. Taking advantage of versatility of silica shell towards different surface modification protocols, the luminomagnetic NPs were successfully functionalized with epidermal growth factor receptor (EGFR) antibody for HepG2 cell recognition. All the results illustrated that the luminomagnetic NPs should be a potential candidate for future cancer diagnosis and therapy.
Materials Science and Engineering C 01/2015; 46:32–40. DOI:10.1016/j.msec.2014.10.002 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Three defect-related luminescent hydroxyapatite (HAP) particles, S1, S2, and S3, with different morphologies (the samples S1 and S2 are nanorods with diameters of 25 nm and lengths of 30 and 100 nm, respectively; sample S3 is bur-like microspheres with diameters of 5-6 μm) were synthesized, and their biocompatibility was investigated by MTT, reactive oxygen species (ROS), interleukin-6 (IL-6), comet, and hemolysis assays. The results indicated that all samples were stable in cell culture medium and did not induce the synthesis of proinflammatory cytokine IL-6 or result in hemolysis. It was found that samples S1 and S3 inhibited osteoblast (OB) viability at concentrations of 5, 10, 20, 40, and 80 μg/mL for 24, 48, and 72 h. Sample S2 had no effect on the viability of OB at all tested concentrations for 24 and 48 h, but the viability of OB was increased at concentrations of 20, 40, and 80 μg/mL for 72 h. Samples S1 and S3 could increase the level of cellular ROS; sample S2 had no effect on the level of cellular ROS at a concentration of 20 μg/mL for 48 h. Although samples S1 and S3 induced significant DNA damage, sample S2 could not cause significant DNA damage at a concentration of 20 μg/mL for 72 h. The results suggest that longer nanorod HAP can show excellent biocompatibility and therefore may find potential applications in biomedical fields.
Biological Trace Element Research 10/2014; 162(1-3). DOI:10.1007/s12011-014-0151-0 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ten novel palladium(II) complexes with dipyrido[3,2-d:2',3'-f]quinoxaline (Dpq)/dipyrido[3,2-a:2',3'-c](6,7,8,9-tetrahydro)phenazine (Dpqc) and 4-toluensulfonyl-L-amino acid dianion, [Pd(Dpq)(TsvalNO)]·H2O (1a), [Pd(Dpq)(TsileNO)]·H2O (1b), [Pd(Dpq)(TsserNO)] (1c), [Pd(Dpq)(TsthrNO)]·1.5H2O (1d), [Pd(Dpq)(TsleuNO)]·0.5H2O (1e), [Pd(Dpq)(TspheNO)] (1f), [Pd(Dpqc)(TsvalNO)] (2a), [Pd(Dpqc)(TsileNO)] (2b), [Pd(Dpqc)(TsserNO)]·H2O (2c) and [Pd(Dpqc)(TsthrNO)]·0.5H2O (2d) have been synthesized and characterized by elemental analysis, IR, UV, (1)H NMR and mass spectrometry techniques. Crystal structure of the complex 1f has been determined by X-ray diffraction. The cytotoxicity was tested by MTT assay. The results indicated that the complexes 1a and 2a showed better cytotoxicity than cisplatin against MCF-7. The complex 1e had higher cytotoxicity than cisplatin against K562. Both the N donating ligands and the amino acid have important effects on the cytotoxicity.
European Journal of Medicinal Chemistry 10/2014; 87C:624-630. DOI:10.1016/j.ejmech.2014.10.002 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
To explore the predictive performance of the newly established visceral adiposity index (VAI) for diabetes and prediabetes, as well as the relationships between the VAI and the parameters of insulin secretion and action.Methods824 first-degree relatives of individuals with type 2 diabetes who had no known history of abnormal glucose regulation were selected. Diabetes and prediabetes were diagnosed using the standard oral glucose tolerance test.ResultsThe VAI values were greater for the subjects with prediabetes and diabetes than for those with normal glucose regulation (NGR). Among the subjects with NGR, the VAI was higher for those whose levels were above the median value of the incremental area under the curve for glucose than for the subjects whose levels fell below the median value. The VAI was negatively correlated with the homeostasis model assessment of the β-cell function index (Homa-β) and with the insulinogenic index (ΔI30/ΔG30). The VAI was found to be a valuable predictor of diabetes, but it was not superior to triglyceride levels, waist circumference, or lipid accumulation production.Conclusions
The first degree relatives of people with type 2 DM who have prediabetes or diabetes have progressively higher VAI in association with progressive hyperglycemia, and it was found to correlate with the Homa-β and the ΔI30/ΔG30. This article is protected by copyright. All rights reserved.
Diabetes/Metabolism Research and Reviews 10/2014; 31(3). DOI:10.1002/dmrr.2615 · 3.55 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 10/2014; 43:330–342. DOI:10.1016/j.msec.2014.07.029 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims
To evaluate the effectiveness of endothelial progenitor cells (EPCs) therapy in ischemia with or without hyperglycemia.
Japanese White Rabbits were randomly assigned to three groups, group SH, hyperglycemia with sham therapy (n = 10); group NE, normoglycemia with autologous EPCs transplantation therapy (n = 12); and group HE, hyperglycemia with autologous EPCs transplantation therapy (n = 12). Hyperglycemia was induced by injecting alloxan and sustained for 12 weeks. Hindlimb ischemia was induced by complete excision of the femoral artery. Ex vivo-expanded EPCs were derived from autologous bone marrow and transplanted intermuscularily in the ischemic hindlimb. Fourteen days after transplantation, the indicators were determined.
There is no difference of the functions of ex vivo-expanded EPCs from autologous bone marrow between normoglycemic and hyperglycemic groups. We found significant improvement in both EPCs transplantation therapy groups compared to sham, in terms of the angiogenesis index (8.62 ± 1.36, 11.12 ± 2.23, 12.35 ± 2.97), capillary density (7.06 ± 0.91, 13.51 ± 1.16, 13.90 ± 2.78), capillary to muscle fiber ratio (0.68 ± 0.09, 0.96 ± 0.11,0.89 ± 0.10), muscle VEGF expression (0.22 ± 0.07, 0.41 ± 0.08, 0.38 ± 0.07 ng/g). We found no significant differences between hyperglycemic and normoglycemic EPCs therapy groups except for 5 pro-angiogenic genes were upregulated in HE as compared to NE.
Ex vivo expanded EPCs from autologous bone marrow transplantation is an effective therapeutic method for hindlimb ischemia in rabbits regardless of glycemic state.
Journal of Diabetes and its Complications 09/2014; 29(1). DOI:10.1016/j.jdiacomp.2014.09.003 · 3.01 Impact Factor
[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 09/2014; 42:70–77. DOI:10.1016/j.msec.2014.04.042 · 3.09 Impact Factor