Jia-Hui Liu

Superior antibacterial activity of zinc oxide/graphene oxide composites originating from high zinc concentration localized around bacteria.

New materials with good antibacterial activity and less toxicity to other species attract numerous research interest. Taking advantage of zinc oxide (ZnO) and graphene oxide (GO), the ZnO/GO composites were prepared by a facile one-pot reaction to achieve superior antibacterial properties without damaging other species. In the composites, ZnO nanoparticles (NPs), with a size of about 4 nm, homogeneously anchored onto GO sheets. The typical bacterium Escherichia coli and HeLa cell were used to evaluate the antibacterial activity and cytotoxicity of the ZnO/GO composites, respectively. The synergistic effects of GO and ZnO NPs led to the superior antibacterial activity of the composites. GO helped the dispersion of ZnO NPs, slowed the dissolution of ZnO, acted as the storage site for the dissolved zinc ions, and enabled the intimate contact of E. coli with ZnO NPs and zinc ions as well. The close contact enhanced the local zinc concentration pitting on the bacterial membrane and the permeability of the bacterial membrane and thus induced bacterial death. In addition, the ZnO/GO composites were found to be much less toxic to HeLa cells, compared to the equivalent concentration of ZnO NPs in the composites. The results indicate that the ZnO/GO composites are promising disinfection materials to be used in surface coatings on various substrates to effectively inhibit bacterial growth, propagation, and survival in medical devices.

Competitive performance of carbon "quantum" dots in optical bioimaging.

Carbon-based “quantum” dots or carbon dots are surface-functionalized small carbon nanoparticles. For bright fluorescence emissions, the carbon nanoparticles may be surface-doped with an inorganic salt and then the same organic functionalization. In this study, carbon dots without and with the ZnS doping were prepared, followed by gel-column fractionation to harvest dots of 40% and 60% in fluorescence quantum yields, respectively. These highly fluorescent carbon dots were evaluated for optical imaging in mice, from which bright fluorescence images were obtained. Of particular interest was the observed competitive performance of the carbon dots in vivo to that of the well-established CdSe/ZnS QDs. The results suggest that carbon dots may be further developed into a new class of high-performance yet nontoxic contrast agents for optical bioimaging.

Effect of size and dose on the biodistribution of graphene oxide in mice

AIM Graphene oxide (GO) has promising applications in bioimaging, diagnostics and therapeutics. This work studied the effects of size and injection dose on the biodistribution of GO to accelerate the development of a GO-based drug. METHODS GO samples were intravenously injected into mice. The content of GO in organs/tissues at different time points was measured using an (125)I-labeling technique. GO in the liver and lungs was further confirmed by both Raman spectroscopic and TEM observations. The dispersion state of GO in serum was evaluated by flow cytometry. RESULTS Regardless of size, GO was cleared from the blood quickly and accumulated mainly in the liver and lungs. The uptake of GO in lungs increased with increasing injection dose and size. The dispersion state (i.e., size of the GO-protein complex in blood) dominated the biodistribution. CONCLUSION The size and dose of GO affected its fate in vivo. For medical applications, small-sized GO with suitable funtionalization is recommended.

Carbon “Quantum” Dots for Fluorescence Labeling of Cells

The specifically synthesized and selected carbon dots of relatively high fluorescence quantum yields were evaluated in their fluorescence labeling of cells. For the cancer cell lines, the cellular uptake of the carbon dots was generally efficient, resulting in the labeling of the cells with bright fluorescence emissions for both one- and two-photon excitations from predominantly the cell membrane and cytoplasm. In the exploration on labeling the live stem cells, the cellular uptake of the carbon dots was relatively less efficient, though fluorescence emissions could still be adequately detected in the labeled cells, with the emissions again predominantly from the cell membrane and cytoplasm. This combined with the observed more efficient internalization of the same carbon dots by the fixed stem cells might suggest some significant selectivity of the stem cells toward surface functionalities of the carbon dots. The needs and possible strategies for more systematic and comparative studies on the fluorescence labeling of different cells, including especially live stem cells, by carbon dots as a new class of brightly fluorescent probes are discussed.

Fluorescent Carbon Dots and Nanodiamonds for Biological Imaging: Preparation, Application, Pharmacokinetics and Toxicity

The rapid advancement of nanotechnology has brought us some new types of fluorescent probes, which are indispensable for bioimaging in life sciences. Because of their innate biocompatibility, good resistance against photobleaching, long fluorescence lifetime and wide fluorescence spectral region, fluorescent carbon quantum dots (C-Dots) and nanosized diamonds (nanodiamonds, NDs) are gradually evolving into promising reagents for bioimaging. In this review, we summarize the recent achievements in fluorescent C-Dots and NDs with emphases on their preparation, properties, imaging application, pharmacokinetics and toxicity. Perspectives on further investigations and opportunities to develop C-Dots and NDs into the safer and more sensitive imaging probes for both living cells and animal models are discussed.

Fullerene-Conjugated Doxorubicin in Cells

The conjugation of fullerene with well-established drug molecules has been a representative strategy to impart fullerene-specific properties for improved formulation. However, conjugates involving fullerenes or other nanomaterials often differ significantly from the free drug molecules in cellular uptake and distributions. For the highly effective anticancer drug doxorubicin (DOX), its strong absorption and fluorescence in the visible spectral region enable the tracking of DOX-containing conjugates by optical techniques. In this work, a stoimetrically and structurally well-defined fullerene-DOX conjugate was studied in terms of fluorescence microscopy, including the fluorescence imaging with two-photon excitation, to examine the uptake and distribution in human breast cancer cells. The results suggested that the conjugate was distributed mostly in the cytoplasm, significantly different from free DOX molecules (predominantly in the cell nucleus, as already reported in the literature). Mechanistic implications of the results are discussed. Also discussed are potentials of conjugated DOX species as self-labeled fluorescent probes in bioimaging and other mechanistic investigations on drug delivery.

Evaluation of the toxicity of food additive silica nanoparticles on gastrointestinal cells

Silica nanoparticles (NPs) have been widely used in food products as an additive; however, their toxicity and safety to the human body and the environment still remain unclear. As a food additive, silica NPs firstly enter the human gastrointestinal tract along with food, thus their gastrointestinal toxicity deserves thorough study. Herein, we evaluated the toxicity of food additive silica NPs to cells originating from the gastrointestinal tract. Four silica NP samples were introduced to human gastric epithelial cell GES‐1 and colorectal adenocarcinoma cell Caco‐2 to investigate the effect of silica sample, exposure dose and exposure period on the morphology, viability and membrane integrity of cells. The cell uptake, cellular reactive oxygen species (ROS) level, cell cycle and apoptosis were determined to reveal the toxicity mechanism. The results indicate that all four silica NPs are safe for both GES‐1 and Caco‐2 cells after 24‐h exposure at a concentration lower than 100 µg ml–1. At a higher concentration and longer exposure period, silica NPs do not induce the apoptosis/necrosis of cells, but arrest cell cycle and inhibit the cell growth. Notably, silica NPs do not pass through the Caco‐2 cell monolayer after 4‐h contact, indicating the low potential of silica NPs to cross the gastrointestinal tract in vivo. Our findings indicate that silica NPs could be used as a safe food additive, but more investigations, such as long‐term in vivo exposure, are necessary in future studies. Copyright

Evaluation of the adjuvant effect of silver nanoparticles both in vitro and in vivo

The immunological adjuvant effect of silver nanoparticles (AgNPs) was investigated both in vitro and in vivo. The in vivo adjuvant effect of AgNPs was evaluated with model antigen ovalbumin (OVA) and bovine serum albumin (BSA) in mice by intraperitoneal and subcutaneous immunization. Serum antigen-specific IgG level significantly increased in AgNPs-treated mice comparing to the control group. AgNPs induced the increase of IgG1/IgG2a ratio and antigen-specific IgE, indicating that AgNPs elicited Th2-biased immune responses. By in vitro assay, the mechanism of adjuvant effect was explored. After 48h treatment with AgNPs, both the number of leukocytes and levels of cytokines TNF-α and IFN-γ in abdominal lavage fluid of mice increased. The expression of the major histocompatibility complex class II molecule on the surface of peritoneal macrophages significantly increased. AgNPs can be easily phagocytosed by peritoneal macrophages, while do not affect antigen uptake by the cell. We therefore conclude that AgNPs have significant adjuvant effect and the mechanism of this effect is mainly ascribed to the recruitment and activation of local leukocytes and especially macrophages. For the first time we found the remarkable adjuvant effect of AgNPs, and the result is beneficial for the future applications, especially in biomedicine.

Biological effect of food additive titanium dioxide nanoparticles on intestine: an in vitro study

Titanium dioxide nanoparticles (TiO2 NPs) are widely found in food‐related consumer products. Understanding the effect of TiO2 NPs on the intestinal barrier and absorption is essential and vital for the safety assessment of orally administrated TiO2 NPs. In this study, the cytotoxicity and translocation of two native TiO2 NPs, and these two TiO2 NPs pretreated with the digestion simulation fluid or bovine serum albumin were investigated in undifferentiated Caco‐2 cells, differentiated Caco‐2 cells and Caco‐2 monolayer. TiO2 NPs with a concentration less than 200 µg ml–1 did not induce any toxicity in differentiated cells and Caco‐2 monolayer after 24 h exposure. However, TiO2 NPs pretreated with digestion simulation fluids at 200 µg ml–1 inhibited the growth of undifferentiated Caco‐2 cells. Undifferentiated Caco‐2 cells swallowed native TiO2 NPs easily, but not pretreated NPs, implying the protein coating on NPs impeded the cellular uptake. Compared with undifferentiated cells, differentiated ones possessed much lower uptake ability of these TiO2 NPs. Similarly, the traverse of TiO2 NPs through the Caco‐2 monolayer was also negligible. Therefore, we infer the possibility of TiO2 NPs traversing through the intestine of animal or human after oral intake is quite low. This study provides valuable information for the risk assessment of TiO2 NPs in food. Copyright

Blood Clearance, Distribution, Transformation, Excretion, and Toxicity of Near-Infrared Quantum Dots Ag2Se in Mice

As a novel fluorescent probe in the second near-infrared window, Ag2Se quantum dots (QDs) exhibit great prospect in in vivo imaging due to their maximal penetration depth and negligible background. However, the in vivo behavior and toxicity of Ag2Se QDs still largely remain unknown, which severely hinders their wide-ranging biomedical applications. Herein, we systematically studied the blood clearance, distribution, transformation, excretion, and toxicity of polyethylene glycol (PEG) coated Ag2Se QDs in mice after intravenous administration with a high dose of 8 μmol/kg body weight. QDs are quickly cleared from the blood with a circulation half-life of 0.4 h. QDs mainly accumulate in liver and spleen and are remarkably transformed into Ag and Se within 1 week. Ag is excreted from the body readily through both feces and urine, whereas Se is excreted hardly. The toxicological evaluations demonstrate that there is no overt acute toxicity of Ag2Se QDs to mice. Moreover, in regard to the in vivo stability problem of Ag2Se QDs, the biotransformation and its related metabolism are intensively discussed, and some promising coating means for Ag2Se QDs to avert transformation are proposed as well. Our work lays a solid foundation for safe applications of Ag2Se QDs in bioimaging in the future.