The prevalent use of engineered nanoparticles (ENPs) has increased our exposure to these particles. The current available analytical techniques fail to simultaneously quantify and analyze the physical properties of ENPs in biological tissues. Therefore, new methods are required to evaluate the exposure conditions to ENPs. Single particle inductively coupled plasma-mass spectrometry (sp-ICP-MS) is an attractive approach that can perform quantitative and qualitative analyses of ENPs. However, the application of this approach for biological samples is limited because of the lack of pretreatment methods for effectively recovering ENPs from biological tissues. In this study, we evaluated various pretreatment methods and identified the optimal pretreatment conditions for sp-ICP-MS analyses of ENPs in biological tissues using silver nanoparticles (nAg) as a model. We screened five reagents as pretreatment solvents (sodium hydroxide, tetramethylammonium hydroxide, nitric acid, hydrochloric acid, and proteinase K). Our results showed that treatment with sodium hydroxide was optimal for detecting nAg in the mouse liver. Moreover, this pretreatment method can be applied to other organs, such as the heart, lung, spleen, and kidney. Finally, we evaluated the applicability of this method by analyzing the quantity and physical properties of silver in the mouse blood and liver, after intravenous administration of nAg or silver ion. Our sp-ICP-MS method revealed that nAg administered into the blood was partially ionized and tended to be distributed in the particle form (approximately 80%) in the liver and in ionic form (approximately 95%) in the blood. In conclusion, we optimized pretreatment strategies for sp-ICP-MS evaluation of ENPs in biological tissues and demonstrated its applicability by evaluating the changes in the physical properties of nAg in the liver and blood. We also showed that partial changes from the particle form to the ionic form of nAg influences their kinetics and distribution when administered to mice.

Microplastics, plastic particles 5 mm or less in size, are abundant in the environment; hence, the exposure of humans to microplastics is a great concern. Usually, the surface of microplastics found in the environment has undergone degradation by external factors such as ultraviolet rays and water waves. One of the characteristics of changes caused by surface degradation of microplastics is the introduction of oxygen-containing functional groups. Surface degradation alters the physicochemical properties of plastics, suggesting that the biological effects of environmentally degraded plastics may differ from those of pure plastics. However, the biological effects of plastics introduced with oxygen-containing functional groups through degradation are poorly elucidated owing to the lack of a plastic sample that imitates the degradation state of plastics found in the environment. In this study, we investigated the degradation state of microplastics collected from a beach. Next, we degraded a commercially available polyethylene (PE) particles via vacuum ultraviolet (VUV) irradiation and showed that chemical surface state of PE imitates that of microplastics in the environment. We evaluated the cytotoxic effects of degraded PE samples on immune and epithelial cell lines. We found that VUV irradiation was effective in degrading PE within a short period, and concentration-dependent cytotoxicity was induced by degraded PE in all cell lines. Our results indicate that the cytotoxic effect of PE on different cell types depends on the degree of microplastic degradation, which contributes to our understanding of the effects of PE microplastics on humans.

Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs), such as osimertinib, show great success in non-small-cell lung cancer patients with EGFR mutated tumors. However, almost all patients develop resistance to EGFR-TKIs owing to secondary EGFR mutations. Although genetic and irreversible resistance mechanisms have been proposed, little is known about non-genetic and reversible resistance mechanisms. From this perspective, a recent study revealed that acute drug exposure generates drug-tolerant persister cells (DTPs) as a form of non-genetic resistance. However, the biological characteristics of DTPs remain unclear. As lipid peroxidation is related to cancer progression and drug resistance, we focused on ferroptosis, namely programmed cell death induced by the accumulation of lipid peroxides, in DTPs. We examined the biological characteristics of ferroptosis in osimertinib-mediated DTPs derived from PC9 lung adenocarcinoma cells. Unlike PC9 cells, established PC9 DTPs were highly sensitive to the ferroptosis inducer RSL3. Accordingly, PC9 DTPs had increased levels of lipid reactive oxygen species and ferrous ion accumulation. Moreover, RSL3-mediated cell death in PC9 DTPs was completely rescued by treatment with the iron chelator deferoxamine. These results suggest that PC9 DTPs showed increased intracellular ferrous ion accumulation and were susceptible to ferroptosis.

Microplastics are ubiquitous in the environment, including in the ocean, soil, and air. Therefore, there are concerns regarding human exposure. Since it is known that the surface of microplastics in various environments is chemically deteriorated by external factors such as ultraviolet rays and waves, it is essential to evaluate the biological effects of degraded microplastics. In this study, we experimented by accelerating the degradation of polyethylene (PE) using vacuum ultraviolet light and prepared PE samples with different degrees of degradation. Then, we evaluated the effects of undegraded and variously degraded PE on cells using cytotoxicity tests. Based on the cytotoxicity test results, we saw a tendency for increased cytotoxicity with increasing degradation. Therefore, this study substantially links the deterioration of microplastics with their biological effects.

Chiral stationary phases based on chicken alpha 1-acid glycoprotein (cAGP) have been used for enantioseparations of various compounds. However, the chiral binding sites and mechanism have not been clarified yet. Based on chromatographic properties of native and W26-modified cAGP columns and docking simulations of studied compounds into the generated model structure of cAGP, the chiral binding sites were located on cAGP and the chiral binding mechanism was discussed. On cAGP, there existed a binding cavity lined with H25, W26, Y47, R128, T129, D161 and E168, which contribute electrostatic or hydrogen bonding interactions. Benzoin and chlorpheniramine enantiomers interacted with cAGP at almost the same sites a little away from W26, while propranolol enantiomers docked, slightly shifting toward H25 and W26. Furthermore, in addition to hydrophobic interactions, ionic interactions between amino groups of chlorpheniramine enantiomers and a carboxyl group of D161 or E168 played an important role in the chiral recognition, while hydrophobic interactions and hydrogen bonding interactions worked for the chiral recognition of benzoin and propranolol enantiomers.