nbo Jia

Induction of Size-Dependent Breakdown of Blood-Milk Barrier in Lactating Mice by TiO2 Nanoparticles

This study aims to investigate the potential nanotoxic effects of TiO2 nanoparticles (TNPs) to dams and pups during lactation period. TiO2 nanoparticles are accumulated in mammary glands of lactating mice after i.v. administration. This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight junction of the blood-milk barrier as indicated by the loss of tight junction proteins and the shedding of alveolar epithelial cells. Compared to larger TNPs (50 nm), smaller ones (8 nm) exhibit a higher accumulation in mammary glands and are more potent in causing perturbations to blood-milk barrier. An alarming finding is that the smaller TNPs (8 nm) are transferred from dams to pups through breastfeeding, likely through the disrupted blood-milk barrier. However, during the lactation period, the nutrient quality of milk from dams and the early developmental landmarks of the pups are not affected by above perturbations.

Oral Exposure to Silver Nanoparticles or Silver Ions May Aggravate Fatty Liver Disease in Overweight Mice

As the applications and environmental release of silver ions and nanoparticles are increasing, increasing human exposure to these pollutants has become an emerging health concern. The impeding effects of such pollutants on susceptible populations are severely under-studied. Here, we demonstrate that silver nanoparticles (Ag NPs), at a dose that causes no general toxicity in normal mice, promotes the progression of fatty liver disease from steatosis to steatohepatitis only in overweight mice. Exposure to Ag+ ions induces the same effects in overweight mice. Ag NPs rather than Ag+ ions cause this disease progression based on our findings that Ag+ ions are partly reduced to Ag NPs in fatty livers, and the toxic effect is correlated with the liver dose of Ag NPs, not Ag+ ions. Furthermore, the Ag NP-induced pro-inflammatory activation of Kupffer cells in the liver, enhancement of hepatic inflammation, and suppression of fatty acid oxidation are identified as key factors in the underlying mechanisms.

Adsorption of bisphenol A to a carbon nanotube reduced its endocrine disrupting effect in mice male offspring.

Soluble carbon nanotubes (CNTs) have shown promise as materials for adsorption of environmental contaminants such as Bisphenol A (BPA), due to the high adsorption capacity and strong desorption hysteresis of BPA on CNTs. The adsorption of BPA to CNTs may change the properties of both BPA and CNTs, and induce different toxicity to human and living systems from that of BPA and CNTs alone. Herein, we report that oral exposure of BPA/MWCNT–COOH (carboxylated multi-walled carbon nantubes) adduct to mice during gestation and lactation period decreased the male offspring reproductive toxicity compared with those induced by BPA alone. The adduct decreased malondialdehyde (MDA) level in testis and follicle-stimulating hormone (FSH) in serum, but increased the level of serum testosterone in male offspring in comparison to BPA alone. Our investigations broadened the knowledge of nanotoxicity and provided important information on the safe application of CNTs.

Mechanistic Understanding of Toxicity from Nanocatalysts

Nanoparticle-based catalysts, or nanocatalysts, have been applied in various industrial sectors, including refineries, petrochemical plants, the pharmaceutical industry, the chemical industry, food processing, and environmental remediation. As a result, there is an increasing risk of human exposure to nanocatalysts. This review evaluates the toxicity of popular nanocatalysts applied in industrial processes in cell and animal models. The molecular mechanisms associated with such nanotoxicity are emphasized to reveal common toxicity-inducing pathways from various nanocatalysts and the uniqueness of each specific nanocatalyst.

Susceptibility of Overweight Mice to Liver Injury as a Result of the ZnO Nanoparticle-Enhanced Liver Deposition of Pb2+

The prevalence of the applications of nanomaterials in consumer products and water treatment facilities increases the chance that humans will be exposed to both nanoparticles and environmental pollutants such as heavy metals. Co-exposure to nanoparticles and heavy metals may adversely affect human health, especially in susceptible populations such as overweight subjects. To evaluate the impact of such co-exposures, we orally administered zinc oxide nanoparticles (ZNPs; 14 or 58 nm) and/or Pb(Ac)2 at tolerable doses to both healthy overweight and healthy normal weight mice. The ZNPs enhanced the deposition of Pb in all major organs in the overweight mice compared with that in the normal mice. As a result, higher levels of hepatic reactive oxygen species, pro-inflammatory cytokines, and liver injury were observed in the overweight mice but not in the normal weight mice. Our findings underscore a potentially enhanced risk of nanoparticle/heavy metal co-exposure in the susceptible overweight population.

Safety Profile of TiO2-Based Photocatalytic Nanofabrics for Indoor Formaldehyde Degradation

Anatase TiO2 nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded TNPs display very little release from nanofabrics (~0.0%) during a standard fastness to rubbing test. Assuming TNPs may fall off nanofabrics during their life cycles, we also examine the possible toxicity of TNPs to human cells. We found that up to a concentration of 220 μg/mL, they do not affect viability of human acute monocytic leukemia cell line THP-1 macrophages and human liver and kidney cells.

Initiation of Targeted Nanodrug Delivery in Vivo by a Multifunctional Magnetic Implant

Implant-mediated targeted drug delivery without an external magnetic field is very challenging. In this work, we report targeted nanodrug delivery initiated by a Fe3O4/poly(lactic-co-glycolic acid) implant scaffold with high magnetism. The implant scaffold is biocompatible and durable. It effectively attracts nanodrugs to its surface, thus killing cancer cells. These findings provide a proof of concept for the magnetic implant-directed nanodrug targeting without the need for an external magnetic field. This approach may further facilitate more precise medical treatments.

Reducing Both Pgp Overexpression and Drug Efflux with Anti-Cancer Gold-Paclitaxel Nanoconjugates.

Repeated administrations of anti-cancer drugs to patients often induce drug resistance. P-glycoprotein (Pgp) facilitates an efficient drug efflux, preventing cellular accumulation of drugs and causing multi-drug resistance (MDR). In this study, we developed a gold-paclitaxel nanoconjugate system to overcome MDR. Gold nanoparticles (GNPs) were conjugated with β-cyclodextrin enclosing paclitaxel (PTX) molecules and PEG molecules. GNP conjugates were effectively endocytosed by both drug-sensitive human lung cancer H460 cells and Pgp-overexpressed drug-resistant H460PTX cells. Compared with PTX, PGNPs did not induce the Pgp overexpression in drug-sensitive H460 cells after long-term treatment and also avoided being pumped out of cells by overexpressed Pgp molecules in H460PTX with a 17-fold lower EC50 compared to PTX. Fluorescent microscopy and flow cytometry further confirmed that fluorescent labeled PGNPs (f-PGNPs) maintained a high cellular PTX level in both H460 and H460PTX cells. These results demonstrated that nano-drug conjugates were able to avoid the development of drug resistance in sensitive cells and evade Pgp-mediated drug resistance and to maintain a high cytotoxicity in drug-resistant cancer cells. These findings exemplify a powerful nanotechnological approach to the long-lasting issue of chemotherapy-induced drug resistance.

Gold Nanoparticle-Induced Cell Death and Potential Applications in Nanomedicine

Cell death is crucial to human health and is related to various serious diseases. Therefore, generation of new cell death regulators is urgently needed for disease treatment. Nanoparticles (NPs) are now routinely used in a variety of fields, including consumer products and medicine. Exhibiting stability and ease of decoration, gold nanoparticles (GNPs) could be used in diagnosis and disease treatment. Upon entering the human body, GNPs contact human cells in the blood, targeting organs and the immune system. This property results in the disturbance of cell function and even cell death. Therefore, GNPs may act as powerful cell death regulators. However, at present, we are far from establishing a structure–activity relationship between the physicochemical properties of GNPs and cell death, and predicting GNP-induced cell death. In this review, GNPs’ size, shape, and surface properties are observed to play key roles in regulating various cell death modalities and related signaling pathways. These results could guide the design of GNPs for nanomedicine.

Elucidation of the Molecular Determinants for Optimal Perfluorooctanesulfonate Adsorption Using a Combinatorial Nanoparticle Library Approach

Perfluorooctanesulfonate (PFOS) persistently accumulates in the environment and in humans, causing various toxicities. To determine the key molecular determinants for optimal PFOS specificity and efficiency, we designed and synthesized a combinatorial gold nanoparticle (GNP) library consisting of 18 members with rationally diversified hydrophobic, electrostatic, and fluorine-fluorine interaction components for PFOS bindings. According to our findings, the electrostatic and F-F interactions between PFOS and nanoparticles are complementary. When F-F attractions are relatively weak, the electrostatic interactions are dominant. As F-F interactions increase, the electrostatic contributions are reduced to as low as 20%, demonstrating that F-F binding may overpower even electrostatic interactions. Furthermore, F-F interactions (28-79% binding efficiency) are 2-fold stronger than regular hydrophobic interactions (15-39% binding efficiency) for PFOS adsorption, explaining why these novel PFOS-binding nanoparticles are superior to other conventional materials based on either hydrophobic or electrostatic binding. The PFOS adsorption by the optimized nanoparticles performs well in the presence of ionic interferences and in environmental wastewater. This library mapping approach can potentially be applied to recognition mechanism investigation of other pollutants and facilitate the discovery of effective monitoring probes and matrices for their removal.