Chang Y

The Toxic Effects and Mechanisms of CuO and ZnO Nanoparticles

Recent nanotechnological advances suggest that metal oxide nanoparticles (NPs) have been expected to be used in various fields, ranging from catalysis and opto-electronic materials to sensors, environmental remediation, and biomedicine. However, the growing use of NPs has led to their release into environment and the toxicity of metal oxide NPs on organisms has become a concern to both the public and scientists. Unfortunately, there are still widespread controversies and ambiguities with respect to the toxic effects and mechanisms of metal oxide NPs. Comprehensive understanding of their toxic effect is necessary to safely expand their use. In this review, we use CuO and ZnO NPs as examples to discuss how key factors such as size, surface characteristics, dissolution, and exposure routes mediate toxic effects, and we describe corresponding mechanisms, including oxidative stress, coordination effects and non-homeostasis effects.

Novel Carbon Nanohybrids As Highly Efficient Magnetic Resonance Imaging Contrast Agents

Novel carbon nanohybrids based on unmodified metallofullerenes have been successfully fabricated for use as a new magnetic resonance imaging (MRI) contrast agent. The nanohybrids showed higher R1 relaxivity and better brightening effect than Gd@C82(OH)X, in T1-weighted MR images in vivo. This is a result of the proton relaxivity from the original gadofullerenes, which retained a perfect carbon cage structure and so might completely avoid the release of Gd3+ ions. A “secondary spin-electron transfer” relaxation mechanism was proposed to explain how the encaged Gd3+ ions of carbon nanohybrids interact with the surrounding water molecules. This approach opens new opportunities for developing highly efficient and low toxicity MRI contrast agents.

Adaption of the structure of carbon nanohybrids toward high-relaxivity for a new MRI contrast agent

Water-soluble GO–Gd@C82 nanohybrids exhibit high relaxivities and could be explored as potential magnetic resonance imaging (MRI) contrast agents. To better understand the relaxation mechanism in the novel carbon nanohybrids, in the present paper, after layers of in-depth analysis and exploration, we propose that the structure and the physicochemical properties of the carbon nanohybrids contribute significantly to the enhanced relaxivity. Better electron transfer from Gd@C82 to the GO nanosheet, appropriate electric conductivity and size of the GO used, an increased number of H proton exchange sites and an adequate concentration of Gd3+ should result in optimal equilibrium for high relaxivity of the GO–Gd@C82. These results are important for constructing and optimizing novel nanoscale architectures with higher relaxivity.

Utilizing Gold Nanoparticle Probes to Visually Detect DNA Methylation

The surface plasmon resonance (SPR) effect endows gold nanoparticles (GNPs) with the ability to visualize biomolecules. In the present study, we designed and constructed a GNP probe to allow the semi-quantitative analysis of methylated tumor suppressor genes in cultured cells. To construct the probe, the GNP surfaces were coated with single-stranded DNA (ssDNA) by forming Au–S bonds. The ssDNA contains a thiolated 5′-end, a regulatory domain of 12 adenine nucleotides, and a functional domain with absolute pairing with methylated p16 sequence (Met-p16). The probe, paired with Met-p16, clearly changed the color of aggregating GNPs probe in 5xa0mol/L NaCl solution. Utilizing the probe, p16 gene methylation in HCT116 cells was semi-quantified. Further, the methylation of E-cadherin, p15, and p16 gene in Caco2, HepG2, and HCT116 cell lines were detected by the corresponding probes, constructed with three domains. This simple and cost-effective method was useful for the diagnosis of DNA methylation-related diseases.

Regulation on mechanical properties of collagen: Enhanced bioactivities of metallofullerol

UNLABELLEDnIncreased mechanical property of extracellular matrix (ECM) around tumor tissue is highly correlated to the progression of cancer, and now its efficient regulation is still a challenge. Here, we report that Gd@C82(OH)22-collagen composites greatly suppress the malignant progression of cancer cells in vitro, and the metallofullerol can efficiently reduce the mechanical property of collagen matrix. Further study indicates that Gd@C82(OH)22 can firmly bind to tropocollagen, facilitate the nuclei and microfibril formation. The interference to interactions among tropocollagens leads to decreased amount and disturbed structure of collagen fibers. C60(OH)24, the fullerol counterpart of Gd@C82(OH)22, is studied in parallel and their impacts on collagen are strikingly modest. The comparison data reveals that the enhanced bioactivity of Gd@C82(OH)22 is highly related with its surface-structure. This study is the first attempt to apply nanomedicines to manipulate the biophysical property of collagen matrix, providing a new sight to target ECM in cancer therapy.nnnFROM THE CLINICAL EDITORnIncreased presence of harder collagen in the extracellular matrix (ECM) around the tumor tissue highly correlates with cancer progression. In this paper, a metallofullerol-based approach is reported as an efficient nanotechnology approach in reducing the mechanical properties of the synthesized collagen, paving the way to the development of novel anti-cancer therapies.

Metabolizer in vivo of fullerenes and metallofullerenes by positron emission tomography

Fullerenes (C60) and metallofullerenes (Gd@C82) have similar chemical structure, but the bio-effects of both fullerene-based materials are distinct in vivo. Tracking organic carbon-based materials such as C60 and Gd@C82 is difficult in vivo due to the high content of carbon element in the living tissues themselves. In this study, the biodistribution and metabolism of fullerenes (C60 and Gd@C82) radiolabeled with (64)Cu were observed by positron emission tomography (PET). (64)Cu-C60 and (64)Cu-Gd@C82 were prepared using 1, 4, 7, 10-tetrakis (carbamoylmethyl)-1, 4, 7, 10-tetra-azacyclodo-decanes grafted on carbon cages as a chelator for (64)Cu, and were obtained rapidly with high radiochemical yield (≥90%). The new radio-conjugates were evaluated in vivo in the normal mouse model and tissue distribution by small animal PET/CT imaging and histology was carried out. The PET imaging, the biodistribution and the excretion of C60 and Gd@C82 indicated that C60 samples have higher blood retention and lower renal clearance than the Gd@C82 samples in vivo and suggested that the differences in metabolism and distribution in vivo were caused by the structural differences of the groups on the fullerene cages though there is chemical similarity between C60 and Gd@C82.

Endocytosed nanoparticles hold endosomes and stimulate binucleated cells formation

BackgroundNanotechnology developed rapidly in cellular diagnosis and treatment, the endocytic system was an important pathway for targeting cell. In the research of developing macrophages as drug carriers or important therapeutic targets, an interesting phenomenon, internalized nanoparticles induced to form binucleated macrophages, was found although the particles dose did not cause obvious cytotoxicity.ResultsUnder 25xa0μg/ml, internalized 30xa0nm polystyrene beads(30xa0nm Ps nanoparticles) induced the formation of binucleated macrophages when they entered into endosomes via the endocytic pathway. These internalized 30xa0nm Ps nanoparticles (25xa0μg/ml) and 30xa0nm Au-NPs (1.575xa0ng/ml) also induced markedly rise of binucleated cell rates in A549, HePG-2 and HCT116. This endosome, aggregated anionic polystyrene particles were dispersed and bound on inner membrane, was induced to form a large vesicle-like structure (LVLS). This phenomenon blocked transport of the particles from the endosome to lysosome and therefore restricted endosomal membrane trafficking through the transport vesicles. Early endosome antigen-1 and Ras-related protein-11 expressions were upregulated; however, the localized distributions of these pivotal proteins were altered. We hypothesized that these LVLS were held by the internalized and dispersed particles decreasing the amount of cell membrane available to support the completion of cytokinesis. In addition, altered distributions of pivotal proteins prevented transfer vesicles from fusion and hampered the separation of daughter cells.Conclusions30xa0nm Ps nanoparticles induced formation of LVLS, blocked the vesicle transport in endocytic system and the distributions of regular proteins required in cytokinesis which led to binucleated cells of macrophages. Markedly raised binucleated rate was also observed in human lung adenocarcinoma epithelial cell line(A549), human hepatoma cell line(HePG-2) and human colorectal cancer cell line(HCT116) treated by 30xa0nm Ps nanoparticles and Au-NPs.

The antihyperlipidemic effects of fullerenol nanoparticles via adjusting the gut microbiota in vivo

BackgroundNanoparticles (NPs) administered orally will meet the gut microbiota, but their impacts on microbiota homeostasis and the consequent physiological relevance remain largely unknown. Here, we describe the modulatory effects and the consequent pharmacological outputs of two orally administered fullerenols NPs (Fol1 C60(OH)7(O)8 and Fol113 C60(OH)11(O)6) on gut microbiota.ResultsAdministration of Fol1 and Fol113 NPs for 4xa0weeks largely shifted the overall structure of gut microbiota in mice. The bacteria belonging to putative short-chain fatty acids (SCFAs)-producing genera were markedly increased by both NPs, especially Fol1. Dynamic analysis showed that major SCFAs-producers and key butyrate-producing gene were significantly enriched after treatment for 7–28xa0days. The fecal contents of SCFAs were consequently increased, which was accompanied by significant decreases of triglycerides and total cholesterol levels in the blood and liver, with Fol1 superior to Fol113. Under cultivation in vitro, fullerenols NPs can be degraded by gut flora and exhibited a similar capacity of inulin to promote SCFA-producing genera. The differential effects of Fol1 and Fol113 NPs on the microbiome may be attributable to their subtly varied surface structures.ConclusionsThe two fullerenol NPs remarkably modulate the gut microbiota and selectively enrich SCFA-producing bacteria, which may be an important reason for their anti-hyperlipidemic effect in mice.

Ultrasmall Superparamagnetic Iron Oxide Nanoparticle for T2-Weighted Magnetic Resonance Imaging

A facile method to synthesize ultrasmall-sized supermagnetic iron oxide nanoparticles with good monodispersity and high relaxivity is desired for magnetic resonance imaging (MRI) technology. Herein, we have developed a one-step method to direct the formation of superparamagnetic iron oxide nanoparticle (uBSPIO) using albumin under mild conditions. The resulting uBSPIO possess ultrasmall size (4.78 ± 0.55 nm) and super high MR relaxivity (444.56 ± 8.82 mM-1 s-1). After grafted by the luteinizing hormone release hormone peptide (LHRH), the uBSPIO could targeted and accumulated in the tumor site. Finally, the uBSPIOs had good stability and did not induce cytotoxicity in vitro or major organ toxicity in vivo. The uBSPIOs are promising contrast agents for MRI.

Small size fullerenol nanoparticles inhibit thrombosis and blood coagulation through inhibiting activities of thrombin and FXa

Thrombus is one of main causes of death in the world and also a vital trouble of biomaterials application in vivo. Recently, effect of fullerenol nanomaterials on anticoagulation was found in our research through extension of bleeding times in treated Sprague-Dawley rats via intravenous injection. Inhibiting of fullerenols on thrombosis was ascertained further by thromboembolism model. Effects of fullerenols on intrinsic and extrinsic pathway were distinct in prolonging activated partial thromboplastin time and prothrombin time, which supported that fullerenols induced defects in both pathways. Inhibited activities of activated coagulation factor X (FXa) and thrombin were verified by experiments in vitro and AutoDock Vina. The results suggest that fullerenols depending on small size and certainly surface property occupied the active domain of FXa and thrombin to block their activity; further, thrombosis was inhibited. This putative mechanism offers an insight into how fullerenol NPs were utilized further in biomedical applications.