Boron-Containing Mesoporous Silica Nanoparticles with Effective Delivery and Targeting of Liver Cancer Cells for Boron Neutron Capture Therapy.

Nanocarriers have been researched comprehensively for the development of novel boron-containing agents in boron neutron capture therapy (BNCT). We designed and synthesized a multifunctional mesoporous silica nanoparticle (MSN)-based boron-containing agent. The latter was coated with a lipid bilayer (LB) and decorated with SP94 peptide (SFSIIHTPILPL) on the surface as SP94-LB@BA-MSN. The latter incorporated boric acid (BA) into hydrophobic mesopores, coated with an LB, and modified with SP94 peptide on the LB. SP94-LB@BA-MSN enhanced nano interface tumor-targeting ability but also prevented the premature release of drugs, which is crucial for BNCT because adequate boron content in tumor sites is required. SP94-LB@BA-MSN showed excellent efficacy in the BNCT treatment of HepG-2 cells. In animal studies with tumor-bearing mice, SP94-LB@BA-MSN exhibited a satisfactory accumulation at the tumor site. The boron content reached 40.18 ± 5.41 ppm in the tumor site 4 h after injection, which was 8.12 and 15.51 times higher than those in mice treated with boronated phenylalanine and those treated with BA. For boron, the tumor-to-normal tissue ratio was 4.41 ± 1.13 and the tumor-to-blood ratio was 5.92 ± 0.45. These results indicated that nanoparticles delivered boron to the tumor site effectively while minimizing accumulation in normal tissues. In conclusion, this composite (SP94-LB@BA-MSN) shows great promise as a boron-containing delivery agent for the treatment of hepatocellular carcinoma using BNCT. These findings highlight the potential of MSNs in the field of BNCT.

Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity.

Understanding the final fate of nanomaterials (NMs) in the liver is crucial for their safer application. As a representative two-dimensional (2D) soft nanomaterial, graphene oxide (GO) has shown to have high potential for applications in the biomedical field, including in biosensing, drug delivery, tissue engineering, therapeutics, etc. GO has been shown to accumulate in the liver after entering the body, and thus, understanding the GO-liver interaction will facilitate the development of safer bio-applications. In this study, the hepatic clearance of two types of PEGylated GOs with different lateral sizes (s-GOs: ~70 nm and l-GOs: ~300 nm) was carefully investigated. We found that GO sheets across the hepatic sinusoidal endothelium, which then may be taken up by the hepatocytes via the Disse space. The hepatocytes may degrade GO into dot-like particles, which may be excreted via the hepatobiliary route. In combination with ICP-MS, LA-ICP-MS, and synchrotron radiation FTIR techniques, we found that more s-GO sheets in the liver were prone to be cleared via hepatobiliary excretion than l-GO sheets. A Raman imaging analysis of ID/IG ratios further indicated that both s-GO and l-GO generated more defects in the liver. The liver microsomes may contribute to GO biotransformation into O-containing functional groups, which plays an important role in GO degradation and excretion. In particular, more small-sized GO sheets in the liver were more likely to be cleared via hepatobiliary excretion than l-GO sheets, and a greater clearance of s-GO will mitigate their hepatotoxicity. These results provide a better understanding of the hepatic clearance of soft NMs, which is important in the safer-by-design of GO.

Selenium-based metabolic oligosaccharide engineering strategy for quantitative glycan detection.

Metabolic oligosaccharide engineering (MOE) is a classical chemical approach to perturb, profile and perceive glycans in physiological systems, but probes upon bioorthogonal reaction require accessibility and the background signal readout makes it challenging to achieve glycan quantification. Here we develop SeMOE, a selenium-based metabolic oligosaccharide engineering strategy that concisely combines elemental analysis and MOE,enabling the mass spectrometric imaging of glycome. We also demonstrate that the new-to-nature SeMOE probes allow for detection, quantitative measurement and visualization of glycans in diverse biological contexts. We also show that chemical reporters on conventional MOE can be integrated into a bifunctional SeMOE probe to provide multimodality signal readouts. SeMOE thus provides a convenient and simplified method to explore the glyco-world.

Isotope dilution LA-ICP-MS for quantitative imaging of trace elements in mouse brain sections.

Isotope dilution (ID) analysis is considered one of the most accurate quantitative methods. However, it has not been widely applied to the quantitative imaging of trace elements in biological samples using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), mainly because of difficulties in homogeneously mixing enriched isotopes (the spike) with the sample (e.g., a tissue section). In this study, we present a novel method for the quantitative imaging of trace elements (copper and zinc) in mouse brain sections using ID-LA-ICP-MS. We used an electrospray-based coating device (ECD) to evenly distribute a known amount of the spike (65Cu and 67Zn) on the sections. The optimal conditions for this process involved evenly distributing the enriched isotopes on mouse brain sections mounted on indium tin oxide (ITO) glass slides using the ECD with the 10 mg g-1 ɑ-cyano-4-hydroxycinnamic acid (CHCA) in methanol at 80 °C. The mass of the spiked isotopes and the tissue sections on the ITO slides was calculated by weighing them on an analytical balance. Quantitative images of Cu and Zn in Alzheimer's disease (AD) mouse brain sections were obtained using ID-LA-ICP-MS. These imaging results showed that Cu and Zn concentrations in various brain regions typically ranged from 10 to 25 µg g-1 and 30-80 µg g-1, respectively. But it is worth noting that the hippocampus contained up to 50 µg g-1 of Zn, while the cerebral cortex and hippocampus had Cu contents as high as 150 µg g-1. These results were validated by acid digestion and solution analysis with ICP-MS. The novel ID-LA-ICP-MS method provides an accurate and reliable means for quantitative imaging of biological tissue sections.

Rosafuningensis (Rosaceae), a new species from Yunnan, China.

A new species Rosafuningensis and its variant R.funingensisf.rosea, both collected from Yunnan Province, China, are, for the first time, documented and illustrated in this study. Morphological analysis in comparison with two related species in the wild, R.gigantea and R.rubus, presents distinguishable features through leaf surfaces, inflorescences and the shape of styles. R.funingensis leaf surfaces are abaxially villous, purple-red, pale green when mature, adaxially glabrous, dark green; inflorescences solitary or 2-5(7) in corymbose cyme; and styles connate into a column or not, exserted.

PEG-GNPs aggravate MCD-induced steatohepatitic injury and liver fibrosis in mice through excessive lipid accumulation-mediated hepatic inflammatory damage.

Rapid development of gold nanoparticles (GNPs) in delivering pharmaceutics and therapeutics approaches still linger the concerns of their toxic effects. Nonalcoholic steatohepatitis (NASH) is characterized by excessive lipid accumulation and overt hepatic inflammatory damage, and is the leading cause of chronic liver disease worldwide. This study aimed to assess the potential hepatic effects of GNPs on NASH phenotype and progression in mice. Mice were fed a MCD diet for 8 weeks to elicit NASH and then intravenously injected with PEG-GNPs at a single dose of 1, 5, and 25 mg/kg-bw. After 24 h and 1 week of administration, the levels of plasma ALT and AST, and the number of lipid droplets, the degree of lobular inflammation and the contents of triglycerides and cholesterols in the livers of the NASH mice significantly increased compared with the untreated NASH mice, indicating that the severity of MCD diet-induced NASH-like symptoms in mice increased after PEG-GNP administration. Moreover, the aggravated hepatic steatosis in a manner involving altered expression of the genes related to hepatic de novo lipogenesis, lipolysis, and fatty acid oxidation was observed after PEG-GNP administration. Additionally, the RNA levels of biomarkers of hepatic pro-inflammatory responses, endoplasmic reticulum stress, apoptosis, and autophagy in MCD-fed mice increased compared with the untreated NASH group. Moreover, PEG-GNP-treated NASH mice displayed an increase in MCD diet-induced hepatic fibrosis, revealed by massive deposition of collagen fiber in the liver and increased expression of fibrogenic genes. Collectively, these results suggest that hepatic GNP deposition after PEG-GNP administration increase the severity of MCD-induced NASH phenotype in mice, which is attributable to, in large part, increased steatohepatitic injury and liver fibrosis in mice.

3D-imaging and quantitative assessment for size-related penetration of HfO2 nanoparticles in breast cancer tumor by synchrotron radiation microcomputed tomography.

The development of quantitative analytical methods to assess the heterogeneous distribution and penetration of nanodrugs in solid tumors is of great importance for anticancer nanomedicine. Herein, Expectation-Maximization (EM) iterate algorithm and threshold segmentation methods were used to visualize and quantify the spatial distribution patterns, penetration depth and diffusion features of two-sized hafnium oxide nanoparticles (s-HfO2 NPs in 2 nm and l-HfO2 NPs in 50 nm sizes) in mouse models of breast cancer using synchrotron radiation micro-computed tomography (SR-µCT) imaging technique. The three-dimensional (3D) SR-µCT images were reconstructed based on the EM iterate algorithm thus clearly displayed the size-related penetration and distribution within the tumors after intra-tumoral injection of HfO2 NPs and X-ray irradiation treatment. The obtained 3D animations clearly show that a considerable amount of s-HfO2 and l-HfO2 NPs diffused into tumor tissues at 2 h post-injection and displayed the obvious increase in the tumor penetration and distribution area within the tumors at day 7 after combination with low-dose X-ray irradiation treatment. A thresholding segmentation for 3D SR-µCT image was developed to assess the penetration depth and quantity of HfO2 NPs along the injection sites in tumors. The developed 3D-imaging techniques revealed that the s-HfO2 NPs presented more homogeneous distribution pattern, diffused more quickly and penetrated more deeply within tumor tissues than the l-HfO2 NPs did. Whereas, the low-dose X-ray irradiation treatment greatly enhanced the wide distribution and deep penetration of both s-HfO2 and l-HfO2 NPs. This developed method may provide quantitative distribution and penetration information for the X-ray sensitive high-Z metal nanodrugs in the cancer imaging and therapy.

A case study on occupational exposure assessment and characterization of particles in a printing shop in China.

Printers can release numerous particles to contaminate indoor environments and pose health risks. Clarifying the exposure level and physicochemical properties of printer-emitted particles (PEPs) will help to evaluate the health risks of printer operator. In our study, the particles concentration in the printing shop was monitored in real time for a long time (12 h/day, total 6 days), and the PEPs were collected to characterize their physicochemical properties including shape, size and compositions. The result showed that the concentration of PEPs is closely related to the printing workload and the highest particle mass concentration of PM10 and PM2.5 was 212.73 µg m-3 and 91.48 µg m-3, respectively. The concentration of PM1 in the printing shop was in the range of 11.88-80.59 µg m-3 for mass value, and 174.83-1348.84 P cm-3 for count value which changed with the printing volume. The particle sizes of PEPs were less than 900 nm, 47.99% of PEPs was less than 200 nm, and 14.21% of the particles were at the nanoscale. PEPs contained 68.92% organic carbon (OC), 5.31% elemental carbon (EC), 3.17% metal elements, and 22.60% other inorganic additives, which contained more OC and metal elements than toners. Total polycyclic aromatic hydrocarbons (PAHs) levels were 18.95 ng/mg in toner and 120.70 ng/mg in PEPs. The carcinogenic risk of PAHs in PEPs was 1.40 × 10-7. These findings suggested future studies should pay more attention to the health effects of printing workers exposed to nanoparticles.

Single-cell multi-element analysis reveals element distribution pattern in human sperm.

Multiple elements in human sperm have been demonstrated to play significant roles in the reproductive process, but their simultaneous detection in single cells remains challenging. We propose a novel analytical procedure using single-cell inductively coupled plasma-time of flight-mass spectrometry (scICP-TOF-MS) to simultaneously quantify multiple elements of individual sperm cells. A promising label-free cell identification strategy based on the endogenous element was developed to obtain valid data. The element contents exhibited varied degrees of heterogeneity in single cells. Machine learning-based analysis of the multi-dimension dataset indicated different distribution patterns and physiological roles among the simultaneously detected elements.

Data analysis for the characterization of nanoparticles with single particle inductively coupled plasma mass spectrometry: From microsecond to millisecond dwell times.

Single particle-inductively coupled plasma-mass spectrometry (SP-ICP-MS) has become a powerful technique for the characterization of nanoparticles (NPs). However, the accuracy of the characterization of NPs by SP-ICP-MS is greatly affected by the data acquisition rate and the way of data processing. For SP-ICP-MS analysis, ICP-MS instruments typically apply microsecond to millisecond dwell times (10 µs-10 ms). Considering the duration of one nanoparticle event in the detector is 0.4-0.9 ms, NPs will show different data forms when working with microsecond and millisecond dwell times. In this work, the effects of dwell times from microsecond to millisecond (50 µs, 100 µs, 1 ms and 5 ms) on the data forms in SP-ICP-MS analysis are discussed. The data analysis and data processing for different dwell times is discussed in detail, including the measurement of transport efficiency (TE), the distinction of signal and background, the evaluation of diameter limit of detection (LODd) and the quantification of mass, size and particle number concentration (PNC) of NPs. This work provides data support for the data processing process and aspects to be considered in the characterization of NPs by SP-ICP-MS, which is expected to provide guidance and reference for researchers in SP-ICP-MS analysis.

Bi-Functionalized Transferrin@MoS2-PEG Nanosheets for Improving Cellular Uptake in HepG2 Cells.

Pre-coating with a protein corona on the surface of nanomaterials (NMs) is an important strategy for reducing non-specific serum protein absorption while maintaining targeting specificity. Here, we present lipoic acid-terminated polyethylene glycol and transferrin bi-functionalized MoS2 nanosheets (Tf@MoS2-PEG NSs) as a feasible approach to enhance cellular uptake. Tf@MoS2-PEG NSs can maintain good dispersion stability in cell culture medium and effectively protect MoS2 NSs from oxidation in ambient aqueous conditions. Competitive adsorption experiments indicate that transferrin was more prone to bind MoS2 NSs than bovine serum albumin (BSA). It is noteworthy that single HepG2 cell uptake of Tf@MoS2-PEG presented a heterogeneous distribution pattern, and the cellular uptake amount spanned a broader range (from 0.4 fg to 2.4 fg). Comparatively, the intracellular Mo masses in HepG2 cells treated with BSA@MoS2-PEG and MoS2-PEG showed narrower distribution, indicating homogeneous uptake in the single HepG2 cells. Over 5% of HepG2 cells presented uptake of the Tf@MoS2-PEG over 1.2 fg of Mo, about three-fold that of BSA@MoS2-PEG (0.4 fg of Mo). Overall, this work suggests that Tf coating enhances the cellular uptake of MoS2 NSs and is a promising strategy for improving the intracellular uptake efficiency of cancer cells.

Renal clearance of graphene oxide: glomerular filtration or tubular secretion and selective kidney injury association with its lateral dimension.

BACKGROUND: Renal excretion is one of the major routes of nanomaterial elimination from the body. Many previous studies have found that graphene oxide nanosheets are excreted in bulk through the kidneys. However, how the lateral size affects GO disposition in the kidneys including glomerular filtration, active tubular secretion and tubular reabsorption is still unknown. RESULTS: The thin, two-dimensional graphene oxide nanosheets (GOs) was observed to excrete in urine through the kidneys, but the lateral dimension of GOs affects their renal clearance pathway and renal injury. The s-GOs could be renal excreted via the glomerular filtration, while the l-GOs were predominately excreted via proximal tubular secretion at a much faster renal clearance rate than the s-GOs. For the tubular secretion of l-GOs, the mRNA level of basolateral organic anion transporters Oat1 and Oat2 in the kidney presented dose dependent increase, while no obvious alterations of the efflux transporters such as Mdr1 and Mrp4 mRNA expression levels were observed, suggesting the accumulation of l-GOs. During the GO renal elimination, mostly the high dose of 15 mg/kg s-GO and l-GO treatment showed obvious kidney injuries but at different renal compartment, i.e., the s-GOs induced obvious glomerular changes in podocytes, while the l-GOs induced more obvious tubular injuries including necrosis of renal tubular epithelial cells, loss of brush border, cast formation and tubular dilatation. The specifically tubular injury biomarkers KIM1 and NGAL were shown slight increase with mRNA levels in l-GO administrated mice. CONCLUSIONS: This study shows that the lateral size of GOs affected their interactions with different renal compartments, renal excretion pathways and potential kidney injuries.

Exploring the performance of quadrupole, time-of-flight, and multi-collector ICP-MS for dual-isotope detection on single nanoparticles and cells.

To meet the demand for multi-element/isotope analysis at the single nanoparticle (NP) or cell level, different types of inductively coupled plasma mass spectroscopy (ICP-MS) have been used to simultaneously monitor multiple mass-to-charge ratios in single-particle/cell ICP-MS (SP/SC-ICP-MS) analysis. Systematic evaluation and comparison of the performance of these techniques are urgently required. Herein, three ICP-quadrupole (Q)-MS, two ICP-time of flight (TOF)-MS, and one multi-collector (MC)-ICP-MS instruments were employed to simultaneously detect 107Ag and 109Ag on single Ag NPs and Ag-exposed cyanobacteria cells. The evaluation was conducted by comparing the measured event-specific 109Ag:107Ag ratios with the natural ratio. Duration of NP or cell events and time resolution in the peak hopping mode were the main factors affecting the performance of ICP-Q-MS. Under the optimal condition (100 µs for both dwell time and settling time), less than 45% of the NP or cell events had a 109Ag:107Ag ratio deviating <30% from the natural ratio. Most events obtained via ICP-TOF-MS were paired events with both isotopes detected. For large-size NPs and cells with high exposure levels, nearly 80% of the events had a ratio deviation within ±30%. MC-ICP-MS performed particularly well in isotope determination with all the events having a ratio deviation within ±5%. For ICP-TOF-MS and MC-ICP-MS, the signal intensity of the events was the main factor affecting the accuracy of the measured 109Ag:107Ag ratios due to the counting statistics. The established methods and results provide insight on the analyses of two elements/isotopes or more on single NPs or cells. Based on the comparison of the advantages and limitations of these instruments, this study provides a critical reference for future multi-element/isotope SP/SC-ICP-MS analyses.

Understanding the Role of the Lateral Dimensional Property of Graphene Oxide on Its Interactions with Renal Cells.

Renal excretion is expected to be the major route for the elimination of biomedically applied nanoparticles from the body. Hence, understanding the nanomedicine-kidney interaction is crucially required, but it is still far from being understood. Herein, we explored the lateral dimension- (~70 nm and ~300 nm), dose- (1, 5, and 15 mg/kg in vivo and 0.1~250 µg/mL in vitro), and time-dependent (48 h and 7 d in vivo) deposition and injury of PEGylated graphene oxide sheets (GOs) in the kidney after i.v. injection in mice. We specially investigated the cytotoxic effects on three typical kidney cell types with which GO renal excretion is related: human renal glomerular endothelial cells (HRGECs) and human podocytes, and human proximal tubular epithelial cells (HK-2). By using in vivo fluorescence imaging and in situ Raman imaging and spectroscopic analysis, we revealed that GOs could gradually be eliminated from the kidneys, where the glomeruli and renal tubules are their target deposition sites, but only the high dose of GO injection induced obvious renal histological and ultrastructural changes. We showed that the high-dose GO-induced cytotoxicity included a cell viability decrease and cellular apoptosis increase. GO uptake by renal cells triggered cellular membrane damage (intracellular LDH release) and increased levels of oxidative stress (ROS level elevation and a decrease in the balance of the GSH/GSSG ratio) accompanied by a mitochondrial membrane potential decrease and up-regulation of the expression of pro-inflammatory cytokines TNF-α and IL-18, resulting in cellular apoptosis. GO treatments activated Keap1/Nrf2 signaling; however, the antioxidant function of Nrf2 could be inhibited by apoptotic engagement. GO-induced cytotoxicity was demonstrated to be associated with oxidative stress and an inflammation reaction. Generally, the l-GOs presented more pronounced cytotoxicity and more severe cellular injury than s-GOs did, demonstrating lateral size-dependent toxicity to the renal cells. More importantly, GO-induced cytotoxicity was independent of renal cell type. The results suggest that the dosage of GOs in biomedical applications should be considered and that more attention should be paid to the ability of a high dose of GO to cause renal deposition and potential nephrotoxicity.

Characterization of titanium dioxide nanoparticles in confectionary products and estimation of dietary exposure level among the Chinese population.

Titanium dioxide (TiO2) is widely used in the food industry. Recently, European Commission has banned TiO2 as a food additive, raising public concern about its health risk, especially the nanoparticles (NPs) contained therein. This study aimed to reveal the existence of TiO2 NPs in food and further estimate the dietary exposure level among Chinese population by characterizing particle size distribution, determining Ti content and micro-distribution in food products, and calculating food consumption from the China Health and Nutrition Survey (CHNS). The results showed that TiO2 particle size in food additives and chewing gums was 53.5-230.3 nm and 56.8-267.7 nm respectively, where NPs accounted for 34.7% and 55.6% respectively. TiO2 was firstly in situ presented on the surface of confectionary products with hard shells. The content of TiO2 ranged from 3.2 to 3409.3 µg/g product. Besides, the mean dietary intake was 71.31 µg/kgbw/day for TiO2 and 7.75 µg/kgbw/day for TiO2 NPs among Chinese population, affected by people's dietary habits of different regions. Children's exposure levels was the highest due to their love of sweets. More attention should be paid to risk assessment and management of TiO2 NPs for children in China.

Impact of Albumin Pre-Coating on Gold Nanoparticles Uptake at Single-Cell Level.

Nanoparticles (NPs) suspension is thermodynamically unstable, agglomeration and sedimentation may occur after introducing NPs into a physiological solution, which in turn affects their recognition and uptake by cells. In this work, rod-like gold NPs (AuNRs) with uniform morphology and size were synthesized to study the impact of bovine serum albumin (BSA) pre-coating on the cellular uptake of AuNRs. A comparison study using horizontal and vertical cell culture configurations was performed to reveal the effect of NPs sedimentation on AuNRs uptake at the single-cell level. Our results demonstrate that the well-dispersed AuNRs-BSA complexes were more stable in culture medium than the pristine AuNRs, and therefore were less taken up by cells. The settled AuNRs agglomerates, although only a small fraction of the total AuNRs, weighed heavily in determining the average AuNRs uptake at the population level. These findings highlight the necessity of applying single-cell quantification analysis in the study of the mechanisms underlying the cellular uptake of NPs.

Gold Nanoparticles Modified With Polyethyleneimine Disturbed the Activity of Drug-Metabolic Enzymes and Induced Inflammation-Mediated Liver Injury in Mice.

Gold nanoparticles (GNPs) have been used as a potential bioactive platform for drug delivery due to their unique optical and thermal characteristics. Liver is the main organ in orchestrating physiological homeostasis through metabolization of drugs and detoxification of exogenous substances. Therefore, it is crucial to deeply understand the mechanism of nanoparticle-liver interaction and the potential hepatic effects of GNPs in vivo. In this study, we studied the hepatic impacts of the intravenously injected polyethyleneimine (PEI)-modified GNPs (PEI-GNPs) on the expression of hepatic drug-metabolic enzymes and sterol responsive element binding protein 1c (SREBP-1c)-mediated de novo lipogenesis in mice for 24 h and 1 week. PEI-GNP accumulation in the liver is associated with increased liver inflammation, as evidenced by the gene expression of pro-inflammatory cytokines. Moreover, the GNP-induced hepatotoxicity in mice is partly due to liver inflammation-triggered disruption in the function of drug-metabolic enzymes, including hepatic uptake and efflux transporters, cytochrome P450 (CYP450), and UDP-glucuronosyltransferases (UGTs). The study provides evidence that it is necessary to consider the nanomaterial-liver interaction and manipulate the surface chemistry of GNPs prior to biomedical application of nanoparticles.

Iron oxide nanoparticles aggravate hepatic steatosis and liver injury in nonalcoholic fatty liver disease through BMP-SMAD-mediated hepatic iron overload.

Nonalcoholic fatty liver disease (NAFLD) is the leading hepatic manifestation of metabolic syndrome worldwide, and is clinically accompanied by iron overload. As the increasing application of iron oxide nanoparticles (IONPs) on the imaging and diagnosis in NAFLD, the potential hepatic effect and mechanism of IONPs on NAFLD should be well studied. Here, we demonstrate that carboxyl-modified (COOH-IONPs) and amino-coated IONPs (NH2-IONPs) exhibit no significant hepatic toxicity in normal mice at the clinical injection dose, but aggravate SREBP-1c-mediated de novo lipogenesis (DNL) in the livers of mice with NAFLD induced by high-fat diet (HFD) and in HepG2 cells incubated with oleic acid (OA), especially in those treated by the positive NH2-IONPs. In the present study, mice receiving IONPs for 7 day show mild iron overload in the liver and exhibit enhanced hepatic inflammation in NAFLD. The BMP-SMAD pathway is initiated by hepatic iron overload and is aggravated in NAFLD. In conclusion, BMP-SMAD-mediated hepatic iron overload aggravated lipid accumulation in the liver and hepatic inflammatory responses, implying that effective measures in addition to hepatic iron overload are needed for individuals at the risk of IONPs in NAFLD.

Multiscale Synchrotron-Based Imaging Analysis for the Transfer of PEGylated Gold Nanoparticles In Vivo.

High spatial resolution imaging analysis is urgently needed to explore the biodistribution, transfer and clearance profiles, and biological impact of nanoparticles in the body, which will be helpful to clarify the efficacy of nanomedicine in clinical applications. Herein, by combination with multiscale synchrotron-based imaging techniques, including X-ray fluorescence (XRF) spectrometry, Fourier transform infrared (FTIR) spectroscopy, and micro X-ray phase contrast computed tomography (micro-XPCT), we visually displayed the transfer patterns and site-specific distribution of PEGylated gold nanoparticles (PEG-GNPs) in the suborgans of the liver, spleen, and kidney after an intravenous injection in mice. A combination of XRF and FTIR imaging analysis showed that the PEG bands presented similar distribution patterns with Au in the intraorgans, suggesting the stability of PEGylation on GNPs. We show that the PEG-GNPs presented heterogeneous distribution in the hepatic lobules with a large amount around the portal vein zone and then a gradient decrease in the sinusoidal region and the CV zone; in the spleen, it gradually accumulated in the splenic red pulp over time; and in the kidney, it quickly transported via the bloodstream to the renal pyramids and renal pelvis, and parts of PEG-GNPs finally accumulated in the renal medulla and renal cortex. Multidimensional micro-XPCT images further show that the PEG-GNP transfer in the liver induced hepatic blood vessel dilatation while they transferred in the liver, providing evidence of GNP transport across the blood vessel endothelial barrier.

Interaction of Humic Acid with Graphene Oxide: Relation to Antibacterial Activities Against Escherichia coli.

Graphene oxide (GO) sheets attracted great attention as effectively antibacterial agents in water treatment and environmental remediation applications. In the study, the interaction of humic acid (HA) as the model of natural organic matter (NOM) with GO and their antibacterial activities against Escherichia coli (E. coli) was investigated. The interaction between GO and HA molecules was analyzed by isothermal titration calorimetry (ITC) and fluorescence spectroscopy analysis. The study demonstrated that GO reaction with HA was a spontaneously exothermic process, which enabled formation of stable and well dispersed GO-HA complex in aqueous solution. Both GO and GO-HA could significantly inhibit the growth of E. coli and present dose-dependent bactericidal property. GO and GO-HA showed more obvious antibacterial activity in saline solution than in LB broth. We suggest the surface wrinkles of GO and GO-HA could contribute to the firm wrapping of E. coli, which is the principle factor for the antibacterial activity of GO and GO-HA. Especially, GO-HA exhibit less surface wrinkles in comparison with GO, corresponding to its reduced antibacterial activity in saline solution.