Gengmei Xing

Mn2+ Dopant-Controlled Synthesis of NaYF4:Yb/Er Upconversion Nanoparticles for in vivo Imaging and Drug Delivery

Pure dark red emission (650-670 nm) of NaYF(4):Yb/Er upconversion nanoparticles (UCNPs) is achieved by manganese ions (Mn(2+)) doping. In addition, the Mn(2+)-doping can also control the crystalline phase and size of the resulting UCNPs simultaneously. Drug delivery studies suggest the promise of these UCNPs as drug carriers for intracellular drug delivery and eventually as a multifunctional nanoplatform for simultaneous diagnosis and therapy.

The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials

We demonstrated that three different types of water-soluble fullerenes materials can intercept all of the major physiologically relevant ROS. C(60)(C(COOH)(2))(2), C(60)(OH)(22), and Gd@C(82)(OH)(22) can protect cells against H(2)O(2)-induced oxidative damage, stabilize the mitochondrial membrane potential and reduce intracellular ROS production with the following relative potencies: Gd@C(82)(OH)(22)> or =C(60)(OH)(22)>C(60)(C(COOH)(2))(2). Consistent with their cytoprotective abilities, these derivatives can scavenge the stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH), and the reactive oxygen species (ROS) superoxide radical anion (O(2)(*-)), singlet oxygen, and hydroxyl radical (HO(*)), and can also efficiently inhibit lipid peroxidation in vitro. The observed differences in free radical-scavenging capabilities support the hypothesis that both chemical properties, such as surface chemistry induced differences in electron affinity, and physical properties, such as degree of aggregation, influence the biological and biomedical activities of functionalized fullerenes. This represents the first report that different types of fullerene derivatives can scavenge all physiologically relevant ROS. The role of oxidative stress and damage in the etiology and progression of many diseases suggests that these fullerene derivatives may be valuable in vivo cytoprotective and therapeutic agents.

Nanotoxicology: Are carbon nanotubes safe?

The toxicity of carbon nanotubes is the subject of ongoing debate. A preliminary study using a small number of mice shows that they may be safe, but the results should be treated with caution.

Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C82(OH)22 and its implication for de novo design of nanomedicine

Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth-leading cause of cancer-related death in North America. Matrix metalloproteinases (MMPs) have long been targeted as a potential anticancer therapy because of their seminal role in angiogenesis and extracellular matrix (ECM) degradation of tumor survival and invasion. However, the inhibition specificity to MMPs and the molecular-level understanding of the inhibition mechanism remain largely unresolved. Here, we found that endohedral metallofullerenol Gd@C82(OH)22 can successfully inhibit the neoplastic activity with experiments at animal, tissue, and cellular levels. Gd@C82(OH)22 effectively blocks tumor growth in human pancreatic cancer xenografts in a nude mouse model. Enzyme activity assays also show Gd@C82(OH)22 not only suppresses the expression of MMPs but also significantly reduces their activities. We then applied large-scale molecular-dynamics simulations to illustrate the molecular mechanism by studying the Gd@C82(OH)22–MMP-9 interactions in atomic detail. Our data demonstrated that Gd@C82(OH)22 inhibits MMP-9 mainly via an exocite interaction, whereas the well-known zinc catalytic site only plays a minimal role. Steered by nonspecific electrostatic, hydrophobic, and specific hydrogen-bonding interactions, Gd@C82(OH)22 exhibits specific binding modes near the ligand-specificity loop S1′, thereby inhibiting MMP-9 activity. Both the suppression of MMP expression and specific binding mode make Gd@C82(OH)22 a potentially more effective nanomedicine for pancreatic cancer than traditional medicines, which usually target the proteolytic sites directly but fail in selective inhibition. Our findings provide insights for de novo design of nanomedicines for fatal diseases such as pancreatic cancer.

Bio-distribution and metabolic paths of silica coated CdSeS quantum dots

With the rapid development of quantum dot (QD) technology, water-soluble QDs have the prospect of being used as a biological probe for specific diagnoses, but their biological behaviors in vivo are little known. Our recent in vivo studies concentrated on the bio-kinetics of QDs coated by hydroxyl group modified silica networks (the QDs are 21.3+/-2.0 nm in diameter and have maximal emission at 570 nm). Male ICR mice were intravenously given the water-soluble QDs with a single dose of 5 nmol/mouse. Inductively coupled plasma-mass spectrometry was used to measure the (111)Cd content to indicate the concentration of QDs in plasma, organs, and excretion samples collected at predetermined time intervals. Meanwhile, the distribution and aggregation state of QDs in tissues were also investigated by pathological examination and differential centrifugation. The plasma half-life and clearance of QDs were 19.8+/-3.2 h and 57.3+/-9.2 ml/h/kg, respectively. The liver and kidney were the main target organs for QDs. The QDs metabolized in three paths depending on their distinct aggregated states in vivo. A fraction of free QDs, maintaining their original form, could be filtered by glomerular capillaries and excreted via urine as small molecules within five days. Most QDs bound to protein and aggregated into larger particles that were metabolized in the liver and excreted via feces in vivo. After five days, 8.6% of the injected dose of aggregated QDs still remained in hepatic tissue and it was difficult for this fraction to clear.

Enhanced Red Emission from GdF3:Yb3+,Er3+ Upconversion Nanocrystals by Li+ Doping and Their Application for Bioimaging

Under 980 nm near-infrared (NIR) excitation, upconversion luminescent (UCL) emission of GdF(3):Yb,Er upconversion nanoparticles (UCNPs) synthesized by a simple and green hydrothermal process can be tuned from yellow to red by varying the concentration of dopant Li(+) ions. A possible mechanism for enhanced red upconverted radiation is proposed. A layer of silica was coated onto the surface of GdF(3):Yb,Er,Li UCNPs to improve their biocompatibility. The silica-coated GdF(3):Yb,Er,Li UCNPs show great advantages in cell labeling and in vivo optical imaging. Moreover, GdF(3) UCNPs also exhibited a positive contrast effect in T(1)-weighted magnetic resonance imaging (MRI). These results suggest that the GdF(3) UCNPs could act as dual-modality biolabels for optical imaging and MRI.

Influences of Structural Properties on Stability of Fullerenols

Influences of structural properties on the stability of fullerenols are studied using experimental techniques including laser-induced dissociation associated with a time-of-flight measurement, synchrotron radiation XPS, and FT-IR spectroscopy. Stabilities of a family of fullerenols (C60(OH)42, C60(OH)44, C60(OH)30, C60(OH)30, C60(OH)32, and C60(OH)36) as functions of structural parameters-the hydroxyl number, intensity of the impure group, and the ratio of the carbonyl to hydroxyl groups-are investigated. It is found that the molecular stability largely depends on the quantity of impure groups, especially the highly oxygenated carbons in fullerenols, but less on the hydroxyl number. This is different from the previous consideration that the stability of fullerenols largely depends on the hydroxyl number. Previously, to gain the larger solubility required by practical applications, it was suggested to increase the number of the hydroxyl groups. This idea needs to be restudied, because in highly hydroxylated fullerenol molecules, the coinstantaneous formation of a large amount of impure groups is observed. The use of C60(OH) n>36 in practical applications should proceed with caution, since these could lead to unstable open-cage structures. The results reveal a way of controlling the formation of impure groups to gain fullerenols of high stability.

Nanoparticles, (Gd@C82(OH)22)n, induces dendritic cell maturation and activates Th1 immune responses

Dendritic cells play a pivotal role in host immune defense, such as elimination of foreign pathogen and inhibition of tumorigenesis. In this paper, we report that [Gd@C(82)(OH)(22)](n) could induce phenotypic maturation of dendritic cells by stimulating DC production of cytokines including IL-12p70, upregulating DC co-stimulatory (CD80, CD83, and CD86) and MHC (HLA-A,B,C and HLA-DR) molecules, and switching DCs from a CCL5-responsive to a CCL19-responsive phenotype. We found that [Gd@C(82)(OH)(22)](n) can induce dendritic cells to become functionally mature as illustrated by their capacity to activate allogeneic T cells. Mice immunized with ovalbumin in the presence of [Gd@C(82)(OH)(22)](n) exhibit enhanced ovalbumin-specific Th1-polarized immune response as evidenced by the predominantly increased production of IFNgamma, IL-1beta, and IL-2. The [Gd@C(82)(OH)(22)](n) nanoparticle is a potent activator of dendritic cells and Th1 immune responses. These new findings also provide a rational understanding of the potent anticancer activities of [Gd@C(82)(OH)(22)](n) nanoparticles reported previously.

Detection of Trace Hg2+ via Induced Circular Dichroism of DNA Wrapped Around Single-Walled Carbon Nanotubes

The strongly induced circular dichroism (ICD) signals of DNA wrapped around single-walled carbon nanotubes (SWCNTs) are shown by the Synchrotron Radiation Facility. In solution, trace amounts of Hg ions have a strong affinity to bind the nucleic bases of DNA-SWCNTs via a pseudo-first-order kinetic reaction. The Hg binding to the bases of DNA results in partial DNA disassociation from the SWCNTs. Such disassociation of DNA from the SWCNTs will decrease the coupling effects of the transition dipole moments between DNA and SWCNTs, thus inducing the ICD signal of DNA-SWCNTs to decrease significantly. Herein, the ICD of DNA-SWCNTs is applied to detect the concentration of Hg ions at nM level.

Gadolinium metallofullerenol nanoparticles inhibit cancer metastasis through matrix metalloproteinase inhibition: imprisoning instead of poisoning cancer cells

UNLABELLED The purpose of this work is to study the antimetastasis activity of gadolinium metallofullerenol nanoparticles (f-NPs) in malignant and invasive human breast cancer models. We demonstrated that f-NPs inhibited the production of matrix metalloproteinase (MMP) enzymes and further interfered with the invasiveness of cancer cells in tissue culture condition. In the tissue invasion animal model, the invasive primary tumor treated with f-NPs showed significantly less metastasis to the ectopic site along with the decreased MMP expression. In the same animal model, we observed the formation of a fibrous cage that may serve as a physical barrier capable of cancer tissue encapsulation that cuts the communication between cancer- and tumor-associated macrophages, which produce MMP enzymes. In another animal model, the blood transfer model, f-NPs potently suppressed the establishment of tumor foci in lung. Based on these data, we conclude that f-NPs have antimetastasis effects and speculate that utilization of f-NPs may provide a new strategy for the treatment of tumor metastasis. FROM THE CLINICAL EDITOR In this study utilizing metallofullerenol nanoparticles, the authors demonstrate antimetastasis effects and speculate that utilization of these nanoparticles may provide a new strategy in metastatic tumor therapy.