Universal Emission Characteristics of Upconverting Nanoparticles Revealed by Single-Particle Spectroscopy.

Upconverting nanoparticles (UCNPs) have been extensively investigated for nanophotonics and biomedical applications. However, establishing a unified view of their emission characteristics to elucidate the underlying photophysics and expand the application fields of these materials is a great challenge due to their sophisticated internal energy transfer and lack of standardized single-particle spectroscopy (SPS) platform. Here, we present an SPS technique called multiband single-particle irradiance-dependent imaging (multiband SPIDI). We demonstrate that the emission characteristics of Yb3+,Tm3+-doped UCNPs are universal for three emission bands over a wide range of irradiance and dependent on the Tm3+ doping concentration, indicating that the number of emitted photons of each band is proportional to the number of activator ions and is dependent on the number of absorbed photons and the activator interionic distance. We also suggest a cooperative energy transfer upconversion (CETU) mechanism for transition to a higher-energy state through photon accumulation. For a single UCNP, the emission at 800 nm is detectable at an ultralow irradiance of 4.9 W cm-2; moreover, that at 450 nm is measurable at 98 W cm-2, based on the optimal concentration. These findings based on the multiband SPIDI platform can provide insights into the interionic energy transfer by studying irradiance-dependent steady-state dynamics to achieve brighter UCNPs and their broader applications.

Monitoring in vivo behavior of size-dependent fluorescent particles as a model fine dust.

BACKGROUND: There has been growing concern regarding the impact of air pollution, especially fine dust, on human health. However, it is difficult to estimate the toxicity of fine dust on the human body because of its diverse effects depending on the composition and environmental factors. RESULTS: In this study, we focused on the difference in the biodistribution of fine dust according to the size distribution of particulate matter after inhalation into the body to predict its impact on human health. We synthesized Cy7-doped silica particulate matters (CSPMs) having different particle sizes and employed them as model fine dust, and studied their whole-body in vivo biodistribution in BALB/c nude mice. Image-tracking and quantitative and qualitative analyses were performed on the ex vivo organs and tissues. Additionally, flow cytometric analysis of single cells isolated from the lungs was performed. Smaller particles with a diameter of less than 100 nm (CSPM0.1) were observed to be removed relatively rapidly from the lungs upon initial inhalation. However, they were confirmed to accumulate continuously over 4 weeks of observation. In particular, smaller particles were found to spread rapidly to other organs during the early stages of inhalation. CONCLUSIONS: The results show in vivo behavioral differences that arisen from particle size through mouse experimental model. Although these are far from the human inhalation studies, it provides information that can help predict the effect of fine dust on human health. This study might provide with insights on association between CSPM0.1 accumulation in several organs including the lungs and adverse effect to underlying diseases in the organs.

Effectual Labeling of Natural Killer Cells with Upconverting Nanoparticles by Electroporation for In Vivo Tracking and Biodistribution Assessment.

Natural killer (NK) cells, which are cytotoxic lymphocytes of the innate immune system and recognize cancer cells via various immune receptors, are promising agents in cell immunotherapy. To utilize NK cells as a therapeutic agent, their biodistribution and pharmacokinetics need to be evaluated following systemic administration. Therefore, in vivo imaging and tracking with efficient labeling and quantitative analysis of NK cells are required. However, the lack of the phagocytic capacity of NK cells makes it difficult to establish breakthroughs in cell labeling and subsequent in vivo studies. Herein, an effective labeling of upconverting nanoparticles (UCNPs) in NK cells is proposed using electroporation with high sensitivity and stability. The labeling performance of UCNPs functionalized with carboxy-polyethylene glycol (PEG) is better than with methoxy-PEG or with amine-PEG. The labeling efficiency becomes higher, but cell damage is greater as electric field increases; thus, there is an optimum electroporation condition for internalization of UCNPs into NK cells. The tracking and biodistribution imaging analyses of intravenously injected NK cells show that the labeled NK cells are initially distributed primarily in lungs and then spread to the liver and spleen. These advances will accelerate the application of NK cells as key components of immunotherapy against cancer.

Self-assembled amphiphilic fluorescent probe: detecting pH-fluctuations within cancer cells and tumour tissues.

Abnormal anaerobic metabolism leads to a lowering of the pH of many tumours, both within specific intracellular organelles and in the surrounding extracellular regions. Information relating to pH-fluctuations in cells and tissues could aid in the identification of neoplastic lesions and in understanding the determinants of carcinogenesis. Here we report an amphiphilic fluorescent pH probe (CS-1) that, as a result of its temporal motion, provides pH-related information in cancer cell membranes and selected intracellular organelles without the need for specific tumour targeting. Time-dependent cell imaging studies reveal that CS-1 localizes within the cancer cell-membrane about 20 min post-incubation. This is followed by migration to the lysosomes at 30 min before being taken up in the mitochondria after about 60 min. Probe CS-1 can selectively label cancer cells and 3D cancer spheroids and be readily observed using the green fluorescence channel (λ em = 532 nm). In contrast, CS-1 only labels normal cells marginally, with relatively low Pearson's correlation coefficients being found when co-incubated with standard intracellular organelle probes. Both in vivo and ex vivo experiments provide support for the suggestion that CS-1 acts as a fluorescent label for the periphery of tumours, an effect ascribed to proton-induced aggregation. A much lower response is seen for muscle and liver. Based on the present results, we propose that sensors such as CS-1 may have a role to play in the clinical and pathological detection of tumour tissues or serve as guiding aids for surgery.

Parental smoking and depression, and attention-deficit hyperactivity disorder in children and adolescents: Korean national health and nutrition examination survey 2005-2014.

INTRODUCTION: We aimed to investigate the risk factors associated with attention-deficit hyperactivity disorder (ADHD) in children and adolescents using a nationally representative sample of the Korean population. METHODS: Data from children and adolescents aged less than 18 years (n = 23 561) were obtained from the Korean National Health and Nutrition Examination Survey, 2005 to 2014. ADHD was assessed using a self-reported diagnosis of ADHD. We estimated the annual prevalence and number of Korean children and adolescents with physician-diagnosed ADHD from 2005 to 2014. We considered various risk factors including demographics, obesity, and family environment (household income, parental age, depression in adults in the household, and exposure to environmental smoke at home). The relationship between ADHD and the considered risk factors was evaluated using multiple logistic regression. RESULTS: The annual prevalence of physician-diagnosed ADHD showed a 4-fold increase (0.35% in 2005 and 1.36% 2014) over the study period. Among ADHD patients, boys and girls constituted 78% and 22%, respectively. Total smoking amounts and depression in adults in the household were significantly associated with children's ADHD. When the analysis was limited to parental effects, only the father's smoking amount and depression were associated with the children's ADHD. DISCUSSION: This study identified adults' smoking and depression as family environmental factors associated with children's ADHD. From a public health care perspective, this result illuminates the need for awareness programs emphasizing a parent's conditions that may influence the development of ADHD in children.