Lin-Yue Lanry Yung

Nanoparticle-induced pulmonary toxicity

In recent decades, advances in nanotechnology engineering have given rise to the rapid development of many novel applications in the biomedical field. However, studies into the health and safety of these nanomaterials are still lacking. The main concerns are the adverse effects to health caused by acute or chronic exposure to nanoparticles (NPs), especially in the workplace environment. The lung is one of the main routes of entry for NPs into the body and, hence, a likely site for accumulation of NPs. Once NPs enter the interstitial air spaces and are quickly taken up by alveolar cells, they are likely to induce toxic effects. In this review, we highlight the different aspects of lung toxicity resulting from NP exposure, such as generation of oxidative stress, DNA damage and inflammation leading to fibrosis and pneumoconiosis, and the underlying mechanisms causing pulmonary toxicity.

Gold nanoparticles in cancer therapy

The rapid advancement of nanotechnology in recent years has fuelled a burgeoning interest in the field of nanoparticle research, in particular, its application in the medical arena. A constantly expanding knowledge based on a better understanding of the properties of gold nanoparticles (AuNPs) coupled with relentless experimentation means that the frontiers of nanotechnology are constantly being challenged. At present, there seems to be heightened interest in the application of AuNPs to the management of cancer, encompassing diagnosis, monitoring and treatment of the disease. These efforts are undertaken in the hope of revolutionizing current methods of treatment and treatment strategies for a multifactorial disease such as cancer. This review will focus on the current applications of AuNPs in cancer management.

Translocation and effects of gold nanoparticles after inhalation exposure in rats

This study was carried out to test the hypothesis that nanogold particles can accumulate in the olfactory bulb, and translocate from the lung to other organs after inhalation exposure. Gold nanoparticles were aerosolized and introduced through an exposure chamber. The number concentration of airborne nano-sized particles was 2×106 #NSPs/cm3 with >75% of particulates between 30 and 110 nm. Exposure for 5 days resulted in significant increase of Au in the lung and olfactory bulb as detected by ICP-MS, but after 15 days, significant accumulation of gold was detected in the lung, esophagus, tongue, kidney, aorta, spleen, septum, heart and blood. Microarray analysis showed downregulation of many genes related to muscle in the nanogold-exposed lung. Lipidomic analysis of the lung showed a specific decrease in phosphatidylserine 36:1 species. We conclude that nanogold is able to translocate from the lung to other organs with time, and causes significant effects in exposed tissues.

Current studies into the genotoxic effects of nanomaterials.

Nanotechnology has created opportunities for engineers to manufacture superior and more efficient devices and products. Nanomaterials (NMs) are now widely used in consumer products as well as for research applications. However, while the lists of known toxic effects of nanomaterials and nanoparticles (NPs) continue to grow, there is still a vast gap in our knowledge about the genotoxicity of NMs. In this paper, we highlight some NMs of interest and discuss the current in vivo and in vitro studies into genotoxic effects of NMs.

Genomic instability of gold nanoparticle treated human lung fibroblast cells

Gold nanoparticles (AuNPs) are one of the most versatile and widely researched materials for novel biomedical applications. However, the current knowledge in their toxicological profile is still incomplete and many on-going investigations aim to understand the potential adverse effects in human body. Here, we employed two dimensional gel electrophoresis to perform a comparative proteomic analysis of AuNP treated MRC-5 lung fibroblast cells. In our findings, we identified 16 proteins that were differentially expressed in MRC-5 lung fibroblasts following exposure to AuNPs. Their expression levels were also verified by western blotting and real time RT-PCR analysis. Of interest was the difference in the oxidative stress related proteins (NADH ubiquinone oxidoreductase (NDUFS1), protein disulfide isomerase associate 3 (PDIA3), heterogeneous nuclear ribonucleus protein C1/C2 (hnRNP C1/C2) and thioredoxin-like protein 1 (TXNL1)) as well as proteins associated with cell cycle regulation, cytoskeleton and DNA repair (heterogeneous nuclear ribonucleus protein C1/C2 (hnRNP C1/C2) and Secernin-1 (SCN1)). This finding is consistent with the genotoxicity observed in the AuNP treated lung fibroblasts. These results suggest that AuNP treatment can induce oxidative stress-mediated genomic instability.

A liquid crystal-based sensor for real-time and label-free identification of phospholipase-like toxins and their inhibitors.

We report a liquid crystal (LC)-based sensor for real-time and label-free identification of phospholipase-like toxins. Beta-bungarotoxin exhibits Ca(2+)-dependent phospholipase A(2) activity whereas alpha-bungarotoxin and myotoxin II do not exhibit any phospholipase activity. The sensor can selectively identify beta-bungarotoxin, when it hydrolyzes a phospholipid monolayer self-assembled at aqueous-LC interface, through orientational responses of LCs. As a result, optical signals that reflect the spatial and temporal distribution of phospholipids during the hydrolysis can therefore be generated in a real-time manner. The sensor is very sensitive and requires less than 5pg of beta-bungarotoxin for the detection. When phospholipase A(2) inhibitors are introduced together with beta-bungarotoxin, no orientational response of LCs can be observed. In addition, the regeneration of the sensor can be done without affecting the sensing performance. This work demonstrates a simple and cost-effective LC-based sensor for identifying phospholipase-like toxins and for screening compound libraries to find potential toxin inhibitors.

Imaging the disruption of phospholipid monolayer by protein-coated nanoparticles using ordering transitions of liquid crystals.

We report an easily visualized liquid crystal (LC)-based system to study the molecular interactions between protein-coated gold nanoparticles (AuNPs) and supported phospholipid monolayer self-assembled at the aqueous-LC interface. Protein-coated AuNPs were found to disrupt the phospholipid monolayer and resulted in the orientational transitions of LCs that support the phospholipid layer. The disruption of the phospholipid monolayer depends on the type of protein (albumin, neutravidin, and fibrinogen) adsorbing onto nanoparticles. Furthermore, our results suggest that hydrophobic interaction plays a major role in the disruption of the phospholipid layer by protein-coated AuNPs. Results obtained from this study may offer new understanding in the potential cytotoxicity of nanomaterials, where the interaction between nanoparticles and cell membrane is an important step.

The induction of epigenetic regulation of PROS1 gene in lung fibroblasts by gold nanoparticles and implications for potential lung injury

Advances in nanotechnology have given rise to the rapid development of novel applications in biomedicine. However, our understanding in the risks and health safety of nanomaterials is still not complete and various investigations are ongoing. Here, we show that gold nanoparticles (AuNPs) significantly altered the expression of 19 genes in human fetal lung fibroblasts (using the Affymetrix Human Gene 1.0 ST Array). Among the differentially expressed genes, up-regulation of microRNA-155 (miR-155) was observed concomitant with down-regulation of the PROS1 gene. Silencing of miR-155 established PROS1 as its possible target gene. DNA methylation profiling analysis of the PROS1 gene revealed no changes in the methylation status of this gene in AuNP-treated fibroblasts. At the ultrastructural level, chromatin condensation and reorganization was observed in the nucleus of fibroblasts exposed to AuNPs. The findings provide further insights into the molecular mechanisms underlying toxicity of AuNPs and their impact on epigenetic processes.

Drosophila melanogaster as a model organism to study nanotoxicity

Abstract Drosophila melanogaster has been used as an in vivo model organism for the study of genetics and development since 100 years ago. Recently, the fruit fly Drosophila was also developed as an in vivo model organism for toxicology studies, in particular, the field of nanotoxicity. The incorporation of nanomaterials into consumer and biomedical products is a cause for concern as nanomaterials are often associated with toxicity in many in vitro studies. In vivo animal studies of the toxicity of nanomaterials with rodents and other mammals are, however, limited due to high operational cost and ethical objections. Hence, Drosophila, a genetically tractable organism with distinct developmental stages and short life cycle, serves as an ideal organism to study nanomaterial-mediated toxicity. This review discusses the basic biology of Drosophila, the toxicity of nanomaterials, as well as how the Drosophila model can be used to study the toxicity of various types of nanomaterials.

Dielectrophoretic capture voltage spectrum for measurement of dielectric properties and separation of cancer cells

In this paper, a new dielectrophoresis (DEP) method based on capture voltage spectrum is proposed for measuring dielectric properties of biological cells. The capture voltage spectrum can be obtained from the balance of dielectrophoretic force and Stokes drag force acting on the cell in a microfluidic device with fluid flow and strip electrodes. The method was demonstrated with the measurement of dielectric properties of human colon cancer cells (HT-29 cells). From the capture voltage spectrum, the real part of Clausius-Mossotti factor of HT-29 cells for different frequencies of applied electric field was obtained. The dielectric properties of cell interior and plasma membrane were then estimated by using single-shell dielectric model. The cell interior permittivity and conductivity were found to be insensitive to changes in the conductivity of the medium in which the cells are suspended, but the measured permittivity and conductivity of cell membrane were found to increase with the increase of medium conductivity. In addition, the measurement of capture voltage spectrum was found to be useful in providing the optimum operating conditions for separating HT-29 cells from other cells (such as red blood cells) using dielectrophoresis.