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Identifying effective reversal agents overcoming multidrug resistance with causal mechanisms from an efflux pump protein is of vital importance for enhanced tumor chemotherapy in clinic. To achieve this end, we construct a metal cluster-based probe, named clusterbody, to develop flow sorting-assisted single-cell mass spectrometry analysis. This clusterbody synthesized by biomimetic mineralization possesses an antibody-like property to selectively recognize an efflux pump protein. The intrinsic red fluorescence emission of the clusterbody facilitates fluorescence-activated high-throughput cell sorting of subpopulations with different multidrug resistance levels. Furthermore, based on the accurate formula of the clusterbody, the corresponding protein abundance at the single-cell level is determined through detecting gold content via precise signal amplification by laser ablation inductively coupled plasma mass spectrometry. Therefore, the effect of reversal agent treatment overcoming multidrug resistance is evaluated in a quantitative manner. This work opens a new avenue to identify reversal agents, shedding light on developing combined or synergetic tumor therapy.

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.

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.

Single-particle inductively coupled plasma-mass spectrometry (SP-ICP-MS) has emerged as an important tool for the characterization of inorganic nanoparticles (NPs) in the environment. Although most SP-ICP-MS applications rely on the quadrupole ICP-MS (ICP-QMS), it is limited by the slow scanning speed of the quadrupole. Recent advancements in instrumentation have led to the development of inductively coupled plasma time-of-flight mass spectrometry (ICP-TOF-MS) which offers a viable solution. In this review, we discuss the recent advances in instrumentation and methodology of ICP-TOF-MS, followed by a detailed discussion of the applications of SP-ICP-TOFMS in analyzing NPs in the environment. SP-ICP-TOFMS has the potential to identify and quantify both anthropogenic and natural NPs in the environment, providing valuable insights into their occurrence, fate, behavior, and potential environmental risks.

Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is an emerging method for the analysis of metal nanoparticles (NPs) in single cells. However, two main obstacles, low analytical throughput and lack of commercial reference materials, need to be overcome. In this work, we demonstrated the principles of a new approach termed "single-cell isotope dilution analysis" (SCIDA) to remove the two obstacles. For a proof of concept, macrophage cells were chosen as a model to study the uptake of silver NPs (AgNPs) at a single-cell level. Single cells exposed to AgNPs were placed in an array by a microfluidic technique; each cell in the array was precisely dispensed with a known picoliter droplet of an enriched isotope solution with a commercial inkjet printer; accurate quantification of AgNPs in single cells was done by using isotope dilution LA-ICP-MS. The average Ag mass of 1100 single cells, 396 ± 219 fg Ag per cell, was in good accord with the average of the population of cells determined by solution ICP-MS analysis. The detection limit was 0.2 fg Ag per cell. The SCIDA approach is expected to be widely applied for the study of cell-NP interactions and biological effects of NPs at the single-cell level.

Two-dimensional (2D) nanosheets (NSs) have a large surface area, high surface free energy, and ultrathin structure, which enable them to more easily penetrate biological membranes and promote adsorption of drugs and proteins. NSs are capable of adsorbing a large amount of blood proteins to form NSs-protein corona complexes; however, their inflammatory effects are still unknown. Therefore, we investigated the pro-inflammatory effect of 2D model nanosheet structures, molybdenum disulfide (MoS2), and the MoS2 NSs-protein complexes with four abundant proteins in human blood, i.e., human serum albumin (HSA), transferrin (Tf), fibrinogen (Fg), and immunoglobulin G (IgG). The interactions between the NSs and the proteins were analyzed by quantifying protein adsorption, determining binding affinity, and correlating structural changes in the protein corona with the uptake of NSs by macrophages and the subsequent inflammatory response. Although all of the NSs-protein complexes induced inflammation, IgG-coated and Fg-coated NSs triggered much stronger inflammatory effects by producing and releasing more cytokines. Among the four proteins, IgG possessed the highest proportion of β-sheets and led to fewer secondary structure changes on the MoS2 nanosheets. This can facilitate uptake and produce a stronger pro-inflammatory response in macrophages due to the recognition of an NSs-IgG complex by Fc gamma receptors and the subsequent activation of the NF-κB pathways. Our results demonstrate that the blood protein components contribute to the inflammatory effects of nanosheets and provide important insights for the nanosafety evaluation and the rational design of nanomedicines in the future.

Herein, the absorption and oxidation reactions of SO2 on TiO2 nanoparticles (TiO2 NPs) at 296 K under various environmental conditions (humidity, UV irradiation, and ozone copresence) were investigated by using a flow chamber reaction system, synchrotron X-ray absorption near-edge structure (XANES) and high resolution synchrotron X-ray photoelectron spectroscopy (XPS) measurements. The results showed that oxidation of SO2 to sulfate via TiO2 NP catalysis happened at a very rapid rate. The appropriate relative humidity, UV irradiation and co-presence of ozone all markedly promoted SO2 oxidation on TiO2 NPs. High resolution XPS unraveled that the terminal hydroxyl (OHt) and oxygen vacancy (VO)–Ti3+ states on TiO2 NPs were the active sites for SO2 adsorption and oxidation. The data of XPS measurements suggest that SO2 was adsorbed on a OHt next to a Ti3+ VO and reacted to form HSO3−. HSO3− can then transform into SO32−via transfer of a proton. The resulting adsorbed SO32− could bind to a surface bridging O (Ob) atom and transform into SO42−. A H2O molecule could dissociate on VO–Ti3+ into two bridging hydroxyl (OHb) groups, subsequently forming new Ob, which provides an active O site for the adsorbed HSO3−/SO32− and oxidizes them into HSO4−/SO42− on the surface of the TiO2 NPs. The copresence of O3 could promote H2O dissociation into OHb, promoting the formation of Ob. The copresence of O3 may also promote the dissociation of adsorbed H2O into TiO2–O2− and hydroxyl radicals (˙OH) on VOs, facilitating the oxidation of adsorbed HSO3−/SO32−. Under UV irradiation, new VOs were created via oxidation of lattice O by photo-generated holes, resulting in increased Ob and subsequently enhanced oxidation of adsorbed HSO3−/SO32− on TiO2 NPs.

Fingerprint analysis is of great significance in forensic sciences. Compared with existing fingerprint analytical methods, mass spectrometry-based methods can not only identify chemical components in fingerprints, but also obtain fingerprint imaging. In this study four kinds of fingerprints, including sweat, inkpad, sunscreen, and liquid foundation, were analyzed by air-flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). AFADESI was employed with air flow of 45 L min−1, and 5 μL min−1 acetonitrile was used as spray solvent at spray voltage of 7000 V. Positive ion full scan mode (100−1000 Da) was chosen. The results showed that AFADESI-MSI method could not only obtain chemical information of various endogenous and exogenous substances in fingerprints, but also obtain high resolution images of fingerprints. In addition, overlapped fingerprints were distinguished according to the typical chemical information in fingerprints. As a new fingerprint analysis method, AFADESI-MSI would be widely used in forensic scientific research and practical applications.

Chemical composition in fingermarks could provide useful information for forensic studies and applications. Here, we evaluate the feasibility of analysis and imaging of fingermarks via elements by synchrotron radiation X-ray fluorescence (SRXRF) and commercial X-ray fluorescence (XRF). As a proof of concept, we chose four brands of sunscreens to make fingermarks on different substrates, including plastic film, glass, paper, and silicon wafer. We obtained an evident image of fingermarks via zinc and titanium by XRF methods. In addition, the ratios of element concentrations in sunscreen fingermarks were obtained, which were in accordance with the results obtained by acid digestion and ICP-OES analysis. In comparison, commercial XRF offers the most advantages in terms of non-destructive detection, easy accessibility, fast element images, and broad applicability. The possibility to acquire fingermark images simultaneously with element information opens up new avenues for forensic science. Graphical abstract.

Silver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials, and they have been applied in various consumer products due to their distinctive antimicrobial properties. Because of cell heterogeneity, the analysis of AgNPs in single cells after exposure is fundamental for biomedical applications or toxicological assays. Here, we developed a high-throughput method for single cell analysis by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Single cells were efficiently trapped by a polydimethylsiloxane (PDMS) microwell array. Under optimal conditions, 60% microwells contained one single cell and 4% microwells contained two cells or more. The cells in the array were regularly distributed; thus, they could be easily targeted and ablated in a grid pattern and quantitatively analyzed by LA-ICP-MS with a high throughput. The silver mass in single 16HBE cells exposed to AgNPs showed log-normal distribution ranging from 0.80 to 383 fg Ag per cell. The average result from single cells was in good agreement with the result from the digestion of 3.0 × 106 cells. The limit of detection (LOD) and limit of quantification (LOQ) were calculated to be 0.2 fg Ag and 0.7 fg Ag, respectively. Because of its great potential in single cell analysis, LA-ICP-MS can be widely applied for single cell analysis and can offer great benefits for the study of the biological effects of metal NPs at the single-cell level.

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.

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

Herein, the absorption and oxidation reactions of SO2 on TiO2 nanoparticles (TiO2 NPs) at 296 K under various environmental conditions (humidity, UV irradiation, and ozone copresence) were investigated by using a flow chamber reaction system, synchrotron X-ray absorption near-edge structure (XANES) and high resolution synchrotron X-ray photoelectron spectroscopy (XPS) measurements. The results showed that oxidation of SO2 to sulfate via TiO2 NP catalysis happened at a very rapid rate. The appropriate relative humidity, UV irradiation and co-presence of ozone all markedly promoted SO2 oxidation on TiO2 NPs. High resolution XPS unraveled that the terminal hydroxyl (OHt) and oxygen vacancy (VO)-Ti3+ states on TiO2 NPs were the active sites for SO2 adsorption and oxidation. The data of XPS measurements suggest that SO2 was adsorbed on a OHt next to a Ti3+ VO and reacted to form HSO3-. HSO3- can then transform into SO32-via transfer of a proton. The resulting adsorbed SO32- could bind to a surface bridging O (Ob) atom and transform into SO42-. A H2O molecule could dissociate on VO-Ti3+ into two bridging hydroxyl (OHb) groups, subsequently forming new Ob, which provides an active O site for the adsorbed HSO3-/SO32- and oxidizes them into HSO4-/SO42- on the surface of the TiO2 NPs. The copresence of O3 could promote H2O dissociation into OHb, promoting the formation of Ob. The copresence of O3 may also promote the dissociation of adsorbed H2O into TiO2-O2- and hydroxyl radicals (˙OH) on VOs, facilitating the oxidation of adsorbed HSO3-/SO32-. Under UV irradiation, new VOs were created via oxidation of lattice O by photo-generated holes, resulting in increased Ob and subsequently enhanced oxidation of adsorbed HSO3-/SO32- on TiO2 NPs.

Two-dimensional (2D) nanosheets (NSs) have a large surface area, high surface free energy, and ultrathin structure, which enable them to more easily penetrate biological membranes and promote adsorption of drugs and proteins. NSs are capable of adsorbing a large amount of blood proteins to form NSs-protein corona complexes; however, their inflammatory effects are still unknown. Therefore, we investigated the pro-inflammatory effect of 2D model nanosheet structures, molybdenum disulfide (MoS

Background To effectively applied nanomaterials (NMs) in medicine, one of the top priorities is to address a better understanding of the possible sub-organ transfer, clearance routes, and potential toxicity of the NMs in the liver and kidney. Results Here we explored how the surface chemistry of polyethylene glycol (PEG), chitosan (CS), and polyethylenimine (PEI) capped gold nanoparticles (GNPs) governs their sub-organ biodistribution, transfer, and clearance profiles in the liver and kidney after intravenous injection in mice. The PEG-GNPs maintained dispersion properties in vivo, facilitating passage through the liver sinusoidal endothelium and Disse space, and were captured by hepatocytes and eliminated via the hepatobiliary route. While, the agglomeration/aggregation of CS-GNPs and PEI-GNPs in hepatic Kupffer and endothelial cells led to their long-term accumulation, impeding their elimination. The gene microarray analysis shows that the accumulation of CS-GNPs and PEI-GNPs in the liver induced obvious down-regulation of Cyp4a or Cyp2b related genes, suggesting CS-GNP and PEI-GNP treatment impacted metabolic processes, while the PEI-GNP treatment is related with immune responses. Conclusions This study demonstrates that manipulation of nanoparticle surface chemistry can help NPs selectively access distinct cell types and elimination pathways, which help to clinical potential of non-biodegradable NPs.

Additional file 1. Additional figures and tables.

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has become a powerful technique for imaging of trace elements in biological samples. However, accurately quantitative imaging is still a complicated task due to lack of matrix-matched standard materials. On the other hand, traditional LA-ICP-MS analysis usually suffers from slow analytical speed and low imaging resolution mainly due to a long washout time of an ablation cell and a low repetition rate of a laser. In this work, a series of homemade matrix-matched standards were produced by homogeneous spiking of gelatin with a known amount of trace elements (Fe, Cu, and Zn). Using these standards, quantitative imaging of Fe, Cu, and Zn in the brains of Alzheimer's disease (AD) and control mice were achieved using a laser ablation system with a low-dispersion cell and a high repetition rate laser coupled to a triple quadrupole ICP-MS. The limits of detection of Fe, Cu, and Zn are 5.4 μg g−1, 0.081 μg g−1, and 0.54 μg g−1, respectively. The concentrations of Fe, Cu, and Zn in mouse brains are 10 ∼ 70 μg g−1, 5 ∼ 30 μg g−1, and 25 ∼ 150 μg g−1, respectively. The quantitative imaging shows different distribution and contents of these metals between AD and control mouse brains. The developed LA-ICP-MS approach is expected to provide a new insight into biological effects of metals and aetiology of metal-related diseases.

Nanomaterials (NMs) as lung-targeted drug delivery vehicles have attracted great attentions. Recent studies indicated that elastic or deformable property of NMs could play a vital role in biomedical applications. Herein, polyvinylpyrrolidone (PVP) functionalized graphene oxide (GO-PVP) via a facile one-pot method and PEGylated GO (GO-PEG) nanosheets (NSs) were synthesized at room temperature. By using rare earth elemental labeling method, we quantitatively revealed that GO-PVP NSs were targeting retention in the lung that after 4 h intravenous injection, the lung/liver and lung/spleen ratios in GO-PVP treated mice were about 230-fold and 30-fold higher of those in GO-PEG treated mice, respectively, especially a considerable amount was retained in the lower respiratory tract including pulmonary interstitium and alveolar region as fibril-like shapes. The florescence imaging and in situ confocal Raman microscopy combining with laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) elemental imaging analysis further confirmed that a more amount of GO-PVP than GO-PEG retention in the pulmonary interstitium. Utilizing atomic force microscopy PeakForce quantitative nanomechanical mapping technique, the nanomechanical property investigation shows that GO-PVP NSs are softer, more adhesive and deformable than GO-PEG NSs. Further, the molecular dynamics simulations illustrate that GO-PVP has deformable structure due to the hydrogen-bond interaction at basal plane between PVP and GO that cause GO-PVP surface roughness and to possess low solvent accessible surface area (SASA), comparatively, the GO-PEG owns relatively firm structure and higher SASA. This study indicates that the well dispersion property and deformable structure of GO-PVP in the lung contribute to its filtration of the endothelial/epithelial barrier and retention in the interstitium and alveolar region. Importantly, the study inspires us to design elastic or deformable NMs in response to the lung disease especially those have occurred in the lower respiratory tract.

Nanotechnology offers significant potential benefits to many fields, including food and agricultural industries, which have opportunities to provide products to the general public that could result in ingested nanoparticles (NPs). Herein, we explored the possible impacts of orally administered TiO 2 NPs, SiO 2 NPs and AgNPs on gut microbiota composition and colitis induction in mice. We administered the NPs to mice at doses of 2.5 mg/kg bw/day for 7 days, which was a dose relevant to human dietary intake for TiO 2 NPs and SiO 2 NPs or the acute oral exposure following medical oral application of AgNPs. No overall toxicity was recorded in mice exposed to TiO 2 NPs and SiO 2 NPs except increased pro-inflammatory cytokine levels (IL-1β, IL-6 and TNF-α) in the colons of mice that ingested SiO 2 NPs. The colitis-like symptoms induced in the mice that ingested AgNPs included high disease activity index and histological scores, disruption of microvilli and tight junctions in the intestinal epithelium, and up-regulation of pro-inflammatory cytokines. Gene analysis by 16S rRNA sequencing showed that AgNP ingestion induced shifts in the intra- and inter-phyla abundance of Bacteroidetes and Firmicutes , reduced the Firmicutes / Bacteroidetes ratio, increased the lowly abundant families of bacteria, and decreased the probiotic bacteria genus Lactobacillus . These results are similar to those reported in studies of other intestinal inflammatory disorders. SiO 2 NP ingestion in mice increased microbial species richness and diversity within the intestinal tract, and in particular, an obvious increase of the genus Lactobacillus was recorded. No obvious disturbance of gut microbiota was found in mice that ingested TiO 2 NPs. The study suggests that alterations in microbiota composition are associated with oral responses to nanoparticle exposure.

Cellular heterogeneity is an inherent condition of cell populations, which results from stochastic expression of genes, proteins, and metabolites. The heterogeneity of individual cells can dramatically influence cellular decision-making and cell fate. So far, our knowledge about how the variation of endogenous metals and non-metals in individual eukaryotic cells is limited. In this study, ICP-MS equipped with a high efficiency cell introduction system (HECIS) was developed as a method of single-cell ICP-MS (SC-ICP-MS). The method was applied to the single-cell analysis of Mn, Fe, Co, Cu, Zn, P, and S in human cancer cell lines (HeLa and A549) and normal human bronchial epithelial cell line (16HBE). The analysis showed obvious variation of the masses of Cu, Fe, Zn, and P in individual HeLa cells, and variation of Fe, Zn, and P in individual A549 cells. On the basis of the single-cell data, a multimodal distribution of the elements in the cell population was fitted, which showed marked differences among the various cell lines. Importantly, subpopulations of the elements were found in the cell populations, especially in the HeLa cancer cells. This study demonstrates that SC-ICP-MS is able to unravel the extent of variation of endogenous elements in individual cells, which will help to improve our fundamental understanding of cellular biology and reveal novel insights into human biology and medicine. Graphical abstract The variations of masses and distribution patterns of elements Mn, Fe, Co, Cu, Zn, P, and S in single cells were successfully detected by ICP-MS coupled with a high efficiency cell introduction system (HECIS).

Graphene oxide (GO) with an extraordinary atomic and electronic structure has germinated into an attractive building block for the design and fabrication of new chiral nanomaterials. Herein, we have synthesized a GO–humic acid (HA) sandwich-type complex that can self-assemble into a twisted, long-range-ordered nanostructure in aqueous media. The GO–HA sandwich complex shows obvious chirality under circular dichroism (CD) measurement. By means of scanning electron microscopy, small-angle X-ray scattering, confocal microscopy, and polarized optical microscopy (POM), the morphology, size, fine texture, and orientation of the assembly nanostructure of GO–HA have been validated. The results of experiments and molecular dynamics simulations reveal that the interactions between GO and HA (via electrostatic repulsive, π–π stacking, hydrogen bond, and solvation) induce the enhanced formation of natural ripples in a single GO–HA sheet, cause interlayer and interdomain distortion, and generate a twisted conformation...

Direct and real-time measurement of nitric oxide (NO) in biological media is very difficult due to its transient nature. Fe3O4 nanoparticles (nanoFe3O4) because of their unique catalytic activities have attracted much attention as catalysts in a variety of organic and inorganic reactions. In this work, we have developed a magnetic Fe3O4 nanoparticle-based rapid-capture system for real-time detection of cellular NO. The basic principle is that the nanoFe3O4 can catalyze the decomposition of H2O2 in the system to generate superoxide anion (O2 ·−) and the O2 ·− can serve as an effective NO· trapping agent yielding peroxynitrite oxide anion, ONOO−. Then the concentration of NO in cells can be facilely determined via peroxynitrite-induced luminol chemiluminescence. The linear range of the method is from 10−4 to 10−8 mol/L, and the detection of limit (3σ, n = 11) is as low as 3.16 × 10−9 mol/L. By using this method, the NO concentration in 0.1 and 0.5 mg/L LPS-stimulated BV2 cells was measured as 4.9 and 11.3 μM, respectively. Surface measurements by synchrotron X-ray photoelectron spectroscopy (SRXPS) and scanning transmission X-ray microscopy (STXM) demonstrate the catalytic mechanism of the nanoFe3O4-based system is that the significantly excess Fe(II) exists on the surface of nanoFe3O4 and mediates the rapid heterogeneous electron transfer, thus presenting a new Fe2O3 phase on the surface.

The present study investigated the size-dependent translocation pattern and biological fate of intranasally instilled nano- and submicron-sized Fe2O3 particles (40 nm and 280 nm) in the CNS. The particle translocation in different parts of brain at 4 h, 12 h, 24 h, 3 d, 7 d, and 30 d after intranasal instillation were quantified using ICP-MS method. A biexponential model (correlation coefficient r = 0.98-0.99) was satisfactory to describe the particokinetic translocation behavior of Fe2O3 nanoparticles in brain. We found a size-dependent translocation pattern and a time-dependent translocation mode for nano- and submicron-sized Fe2O3 nanoparticles in the olfactory bulb, which are most significant in toxic concerns of nanoparticles in the CNS. The TEM images showed particle-like substances of approximately 35-50 nm were located in the axons of olfactory neurons and in the mitochondria and lysosomes of hippocampus cells in the 40 nm-Fe2O3 exposed mice. The synchrotron-based near-edge X-ray absorption spectroscopy (XANES) was used to identify the chemical forms of the nanoparticles in brain. The XANES results indicate that the presence of chemical speciation of the Fe2O3 nanoparticle (-17%) and protein-complex like apotransferrin-Fe2O3 (-16%) in the olfactory bulb, implying that self-coating of Fe2O3 nanoparticles with transferrin occurred in brain. All the findings suggest size-sensitive manners of nano- and submicron-sized Fe2O3 particles in the brain; the smaller one possesses evident detention properties in the CNS versus the larger one.

Liver is the major organ in the metabolization of drugs, and detoxification of exogenous substances, including nanoparticles. In clinical medical practice, drug-induced liver injury (DILI) is the major cause of acute liver failure (ALF). In this study, we explore the possible impact of intravenously injected citrate acid (CA), chitosan (CS) and polyethyleneglycol (PEG) functionalized gold nanoparticles (GNPs) on the liver of mice at the doses (60 and 120 μg/mouse) relevant to their biomedical applications. Overall, the results provide the evidence that all the GNPs did not induce obvious liver injury and hepatic steatosis in mice. However, the study highlights that alteration in the function of drug-metabolizing enzymes in the HepaRG cells was associated with the increase cytotoxicity of GNP treatments. Moreover, the deposited GNPs in the liver disturb the expression of drug-metabolizing enzymes, including drug uptake and efflux transporters, and cytochrome P450 (CYP450) isoforms and phase II metabolized enzymes. The mechanism of GNP-induced hepatotoxicity in mice is associated with hyperactivation of mTOR signalling and SREBP-1c-mediated de novo lipogenesis with hepatic inflammation. This also suggests that when using GNPs for biomedical applications, it is necessary to consider the influence of nanomaterial-liver interaction and nanomaterial-induced hepatotoxicity on drug-metabolizing enzymes and lipid homeostasis.

Understanding the pharmacokinetics, distribution, and the behavior underlying the transfer and clearance of graphene oxide (GO) in vivo is critical for its clinical translation. However, GO is a single-atomic layered nanomaterial comprised only of carbon, hydrogen, and oxygen molecules, tracking GO in vivo is difficult. In this study, we developed a novel dual-element labelling strategy using the two rare-earth elements lanthanum (La) and cerium (Ce) as tags on polyvinylpyrrolidone (PVP) modified GO (La/Ce-GO-PVP) to successfully track the bioaccumulation, transfer, and clearance of GO in vivo. The data showed that intravenously injected La/Ce-GO-PVP nanosheets could be rapidly intercepted by the mononuclear phagocyte system rich organs (lung, liver, and spleen) and the kidney. A visual exploration for La/Ce-GO-PVP transfer and clearance in intra-organs and ultrastructure of the organs by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and transmission electron microscopy (TEM) was performed. The thin, flexible, and well-dispersed GO-PVP was observed to enter into the deep sub-organs of the lung, liver and spleen, pass through the glomerular filtration barrier (GFB) of the kidney and was excreted in the urine. In addition, we observed the GO nanosheets by rolling, crumpling or folding their morphology to facilitate their transfer across the continuous, fenestrated, and discontinuous endothelium, where GO can then be transferred and cleared in the intra-organs. This study provides a further understanding for the thin and flexible GO transfer and clearance in vivo, and the interactions with physiological barriers in view of their potential biomedical applications.

To explore the effects of hexavalent chromium [Cr(VI)] on apolipoprotein(Apo) metabolism.One hundred and six long-term Cr(VI) exposed subjects and fifty five non-exposed individuals were recruited. The blood metals, glucose and lipid parameters were measured to evaluate the effects of hexavalent chromium on the apolipoproteins.The quantity and homeostasis of multi-elements were significantly different between Cr(VI)exposed subjects and the controls(P 0.05). The levels of serum TG, FPG, LDL-C, Apo AI, AII, CII, CIII, E and Lp(a) also changed significantly (P 0.05). Concentration of chromium in whole blood and erythrocytes had different relationships with serum apolipoprotein levels in Cr(VI)exposed subjects.Exposure of hexavalent chromium could significantly change the homeostasis of multi-elements as well as the levels of serum apolipoproteins. Cr(III) and Cr(VI)may have different effects on the apolipoproteins.

Polyethylene glycol (PEG) has been frequently used for surface modification of nanoparticles (NPs) to reduce non-specific binding of proteins on NPs. The investigation of protein absorption on PEGylated nanoparticles is necessary. In the work, the conjugation of transferrin (Tf) to PEGylated AuNPs via adsorption or bonding was studied. The 13 nm AuNPs were coated with various molecular weight (300, 2000, 5000) carboxyl and methoxy PEG thiol. The presence of Tf on PEGylated AuNP was characterized by dynamic light scattering (DLS) and infrared spectroscopy (IR). The data of IR confirmed the presence of Tf on PEGylated AuNPs. The diameter decrease of PEGylated AuNPs after Tf adsorption was observed by DLS measurement, which is attributed to competitive adsorption between Tf and PEG molecules. These phenomena may be important to the preservation of Tf targeting specificity on PEGylated AuNPs.

Characterization of bio-nano interface is crucial for developing safer and more efficient nanoparticles in nanomedical application. PEGylation is commonly used in nanocarrier for drug delivery, as it confers nanoparticles good stability, stealth effect and better targeting specificity compared with those without PEGylation. However, the protein binding state on PEGylated AuNP is still limited known. In present work, we prepared 13 nm AuNPs and then PEGylated them with thiol PEG methoxy. Lysozyme is selected as a model protein and to investigate the interactions on protein-PEGylated/AuNP interface. The thermal unfolding processes of lysozyme in absence and presence of PEGylated AuNP were measured by synchrotron radiation based circular dichroism (SRCD), dynamic light scattering (DLS) and infrared spectroscopy (IR). The results suggest that in terms of secondary structural changes, α helix content is decreased, while β sheet content is increased, and thus the adsorbed lysozyme may be present in PEG layer.

Amyloid fibrillation has been implicated in many neurodegenerations, dialysis-related amyloidosis, type II diabetes and more than 30 other amyloid-related diseases. Nanomaterials as potential inhibitors of amyloid fibrillation have attracted increasing interests. In the present study, the effects of gold nanorods (AuNRs) and nanoparticles (AuNPs) on amyloid fibrillation were investigated using hen egg white lysozyme (HEWL) as a model system. Our results indicated that AuNRs and AuNPs, especially AuNRs, present significant inhibitory effects on HEWL amyloid fibril formation during all the kinetic processes, from nucleation to elongation and equilibration stages. The stronger adsorption capacity of HEWL on AuNRs surface is the key mechanism of inhibition of HEWL amyloid fibrillation. Furthermore, AuNRs lead to more stable α-helix conformation and hydrophobic microenvironment of aromatic side groups in HEWL molecules, which facilitate the system to form small amorphous aggregates rather than oligomer, profibril or mature fibril.

Single walled carbon nanotubes (SWCNTs) have been shown to be highly effective against a wide range of bacteria. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) infection is a well-known mediator to prolong hospitalization and initiate chronic inflammation, yet the biological effects of SWCNTs on the pathogen-infected enterocytes remain unclear. Herein, it is shown that the low-dose SWCNT treatment attenuates the human enterocyte-like Caco-2 cells from the damage of E. coli and S. aureus infection by suppressing NLRP3 inflammasome activation. The relatively low-dose (1 and 10 mu g mL(-1)) SWCNT treatments reduce the adhesion and invasion of E. coli and S. aureus to Caco-2 cells, increase the cell viability and proliferation, reduce the tight junction permeability, and restitute the integrity of cell surface microvilli structure, meanwhile has low cytotoxicity to the host cells. The low-dose SWCNT treatment further reduces the NLRP3-mediated IL-1 beta secretion in the infected cells. The results identify that a low-dose SWCNT treatment serves a protective function for the E. coli- and S. aureus-infected Caco-2 cells by negatively regulating mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation.

Understanding the interactions of nanomaterials (NMs) with biomolecules, organelles, cells, and organic tissues at the nano-bio interface can offer important information for their uptake, distribution, translocation, metabolism and degradation in vitro and in vivo, which can help to precisely tune and design “smart” NMs for biomedical applications. However, probing the interactions at the nano-bio interface, which generally requires dedicated analytical methods and tools, is remarkably complicated due to the dynamically changed nature of the nano-bio interface. Because of the advantages of high spatial resolution, high sensitivity, excellent accuracy, low matrix effects and non-destructiveness, synchrotron radiation (SR)-based analytical techniques have become extremely valuable tools. Herein, we present a comprehensive overview of SR-based techniques for the visualized study of NMs at cellular and subcellular interfaces and their transformation in vitro; the exploration of biodistribution, translocation, metabolism and degradation of NMs in vivo; and clarification of the molecular mechanisms of NMs’ reactions with biomolecules. Rapid development of advanced light source means that in situ, real-time analysis of NMs at the nano-bio interface will be achieved.

Cisplatin is a commonly used chemotherapeutic drug in cancer treatment, whereas Gd@C82(OH)22 is a new nanomaterial anti-tumor agent. In this study, we determined intracellular Gd@C82(OH)22 and cisplatin after treatment of Hela and 16HBE cells by single cell inductively coupled plasma-mass spectrometry (SC-ICP-MS), which could provide quantitative information at a single-cell level. The cell digestion method validated the accuracy of the SC-ICP-MS. The concentrations of Gd@C82(OH)22 and cisplatin in cells at different exposure times and doses were studied. The SC-ICP-MS is a promising complement to available methods for single cell analysis and is anticipated to be applied further to biomedical research.

We report for the first time seeing and counting integrin α(IIb)β3 on a single-cell level. The proposed method is based on the using of the Au cluster probe. With the fluorescent property of Au24 cluster and the specific targeting ability of peptide, our probe can directly visualize integrin α(IIb)β3 on the membrane of human erythroleukemia cells (HEL) via confocal microscopy. On the basis of the accurate formula of our probe (Au24Peptide8), the number of integrin α(IIb)β3 can be precisely counted by quantifying the gold content on a single HEL cell via laser ablation inductively coupled plasma mass spectrometry. Our results reveal that the number of integrin α(IIb)β3 on a single cell varies from 5.75 × 10(-17) to 9.11 × 10(-17) mol, because of the heteroexpression levels of α(IIb)β3 on individual cells.

Preparation of heterogeneous catalysts with active ferrous centers is of great significance for industrial and environmental catalytic processes. Nanostructured carbon materials (NCM), which possess free-flowing p electrons, can coordinate with transition metals, provide a confinement environment for catalysis, and act as potential supports or ligands to construct analogous complexes. However, designing such catalysts using NCM is still seldom studied to date. Herein, we synthesized a sandwich structured ternary complex via the coordination of Fe-loaded humic acid (HA) with C=C bonds in the aromatic rings of carbon nanotubes (CNTs), in which the O/N-Fe-C interface configuration provides the confinement environment for the ferrous sites. The experimental and theoretical results revealed octahedrally/tetra-hedrally coordinated geometry at Fe centers, and the strong hybridization between CNT C pi* and Fe 3d orbitals induces discretization of the atomic charges on aromatic rings of CNTs, which facilitates O-2 adsorption and electron transfer from carbon to O-2, which enhances O-2 activation. The O-2 activation by the novel HA/Fe-CNT complex can be applied in the oxidative degradation of phenol red (PR) and bisphenol A (BPA) in aqueous media.