Bifunctional Mo2N Nanoparticles with Nanozyme and SERS Activity: A Versatile Platform for Sensitive Detection of Biomarkers in Serum Samples.

The combined application of nanozymes and surface-enhanced Raman scattering (SERS) provides a promising approach to obtain label-free detection. However, developing nanomaterials with both highly efficient enzyme-like activity and excellent SERS sensitivity remains a huge challenge. Herein, we proposed one-step synthesis of Mo2N nanoparticles (NPs) as a "two-in-one" substrate, which exhibits both excellent peroxidase (POD)-like activity and high SERS activity. Its mimetic POD activity can catalyze the 3,3',5,5'-tetramethylbenzidine (TMB) molecule to SERS-active oxidized TMB (ox-TMB) with high efficiency. Furthermore, combining experimental profiling with theory, the mechanism of POD-like activity and SERS enhancement of Mo2N NPs was explored in depth. Benefiting from the outstanding properties of Mo2N NPs, a versatile platform for indirect SERS detection of biomarkers was developed based on the Mo2N NPs-catalyzed product ox-TMB, which acts as the SERS signal readout. The feasibility of this platform was validated using glutathione (GSH) and target antigens alpha-fetoprotein antigen (AFP) and carcinoembryonic antigen (CEA) as representatives of small molecules with a hydroxyl radical (·OH) scavenging effect and proteins with a low Raman scattering cross-section, respectively. The limits of detection of GSH, AFP, and CEA were as low as 0.1 µmol/L, 89.1, and 74.6 pg/mL, respectively. Significantly, it also showed application in human serum samples with recoveries ranging from 96.0 to 101%. The acquired values based on this platform were compared with the standard electrochemiluminescence method, and the relative error was less than ±7.3. This work not only provides a strategy for developing highly active bifunctional nanomaterials but also manifests their widespread application for multiple biomarkers analysis.

Modulating the Coordination Environment of Carbon-Dot-Supported Fe Single-Atom Nanozymes for Enhanced Tumor Therapy.

Herein, carbon dot (CD)-supported Fe single-atom nanozymes with high content of pyrrolic N and ultrasmall size (ph-CDs-Fe SAzyme) are fabricated by a phenanthroline-mediated ligand-assisted strategy. Compared with phenanthroline-free nanozymes (CDs-Fe SAzyme), ph-CDs-Fe SAzyme exhibit higher peroxidase (POD)-like activity due to their structure similar to that of ferriporphyrin in natural POD. Aberration-corrected high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and X-ray absorption fine structure spectroscopy (XAFS) analyses show that metal Fe is dispersed in ph-CDs-Fe SAzyme as single atoms. Steady-state kinetic studies show that the maximum velocity (Vmax ) and turnover number (kcat ) of H2 O2  homolytic cleavage catalyzed by ph-CDs-Fe SAzyme are 3.0 and 6.2 more than those of the reaction catalyzed by CDs-Fe SAzyme. Density functional theory (DFT) calculations show that the energy barrier of the reaction catalyzed by ph-CDs-Fe SAzyme is lower than that catalyzed by CDs-Fe SAzyme. Antitumor efficacy experiments show that ph-CDs-Fe SAzyme can efficiently inhibit the growth of tumor cells both in vitro and in vivo by synergistic chemodynamic and photothermal effects. Here a new paradigm is provided for the development of efficient antitumor therapeutic approaches based on SAzyme with POD-like activity.

FeSA­Ir/Metallene Nanozymes Induce Sequential Ferroptosis­Pyroptosis for Multi­Immunogenic Responses Against Lung Metastasis.

For cancer metastasis inhibition, the combining of nanozymes with immune checkpoint blockade (ICB) therapy remains the major challenge in controllable reactive oxygen species (ROS) generation for creating effective immunogenicity. Herein, new nanozymes with light-controlled ROS production in terms of quantity and variety are developed by conjugating supramolecular-wrapped Fe single atom on iridium metallene with lattice-strained nanoislands (FeSA-Ir@PF NSs). The Fenton-like catalysis of FeSA-Ir@PF NSs effectively produced •OH radicals in dark, which induced ferroptosis and apoptosis of cancer cells. While under second near-infrared (NIR-II) light irradiation, FeSA-Ir@PF NSs showed ultrahigh photothermal conversion efficiency (𝜂, 75.29%), cooperative robust •OH generation, photocatalytic O2 and 1O2 generation, and caused significant pyroptosis of cancer cells. The controllable ROS generation, sequential cancer cells ferroptosis and pyroptosis, led 99.1% primary tumor inhibition and multi-immunogenic responses in vivo. Most importantly, the inhibition of cancer lung metastasis is completely achieved by FeSA-Ir@PF NSs with immune checkpoint inhibitors, as demonstrated in different mice lung metastasis models, including circulating tumor cells (CTCs) model. This work provided new inspiration for developing nanozymes for cancer treatments and metastasis inhibition.

Tunable random lasers via phase transition for information encryption.

Introducing phase transition materials to random systems provides a promising route to create new optoelectronic functionalities of random lasers. Here, a phase transition random laser with switchable lasing modes is reported, which is designed with a thermoresponsive hydrogel as scattering medium. By manipulating the phase transition in hydrogel, random lasing modes can be switched reversibility between incoherent and coherent random lasing. The phenomenon derives from the changing of light scattering properties in different phase states, thus affecting the optical feedback path of random lasing. Besides, based on its controllable and easily detectable time-domain characteristics, the phase transition random laser is applied in information encoding and transmission. It is the first time that the transition from coherent to incoherent random lasing is observed by varying the sample phase states. This work will inspire the design and application of novel random lasers in photoelectric device.

Switchable whispering gallery mode lasing via phase transition.

Combining phase-transition materials with optical microcavities may advance the applications of whispering-gallery mode (WGM) lasing in performance customization, sensing, and optical switching. In this study, switchable WGM lasing based on phase transition is reported. The device is designed by introducing the phase-transition hydrogel into the capillary microcavity. After approaching the phase-transition point in hydrogel, the number of WGM lasing modes decreases sharply with a significant blueshift in the wavelength. The phenomenon is caused by the increase in light scattering and decrease in effective refractive index of the device. Furthermore, single-mode lasing is obtained by manipulating the phase transition, which exhibits superior reversibility. This study may pave the way for designing and multifunctioning of novel WGM lasing in photonic devices.

A method for quantifying hepatic and intestinal ceramides on mice by UPLC-MS/MS.

BACKGROUND: Ceramide is one type of sphingolipids, is associated with the occurrence of metabolic diseases, including obesity, diabetes, cardiovascular disease, cancer, and nonalcoholic fatty liver disease. Dihydroceramide, the direct precursors of ceramide, which is converted to ceramide with the dihydroceramide desaturase, is recently regarded as involving in various biological processes and metabolic diseases. The liver and gut ceramide levels are interactional in pathophysiological condition, quantifying hepatic and intestinal ceramide levels become indispensable. The aim of this study is to establish a rapid method for the determination of ceramides including dihydroceramides in liver and small intestinal tissues for researching the mechanisms of ceramide related diseases. METHODS: The levels of Cer d18:1/2:0, Cer d18:1/6:0, Cer d18:1/12:0, Cer d18:1/14:0, Cer d18:1/16:0, Cer d18:1/17:0, Cer d18:1/18:0, Cer d18:1/20:0, Cer d18:1/22:0, Cer d18:1/24:1, Cer d18:1/24:0, dHCer d18:0/12:0, dHCer d18:0/14:0, dHCer d18:0/16:0, dHCer d18:0/18:0, dHCer d18:0/24:1 and dHCer d18:0/24:0 in mice liver and small intestine were directly quantified by ultra-high performance liquid chromatography-tandem mass spectrometry after methanol extraction. In detail, liver or small intestine tissues were thoroughly homogenized with methanol. The resultant ceramides were separated on a Waters BEH C18 column using gradient elution within 10 min. Positive electrospray ionization with multiple reaction monitoring was applied to detect. In the end, the levels of ceramides in mice liver and small intestine tissues were quantified by this developed method. RESULTS: The limits of detection and quantification of 11 ceramides and 6 dihydroceramides were 0.01-0.5 ng/mL and 0.02-1 ng/mL, respectively, and all detected ceramides had good linearities (R2 > 0.997). The extraction recoveries of ceramides at three levels were within 82.32%-115.24% in the liver and within 83.21%-118.70% in the small intestine. The relative standard deviations of intra- and inter-day precision were all within 15%. The extracting solutions of the liver and small intestine could be stably stored in the autosampler 24 h at 10 °C, the lyophilized liver and small intestine for ceramides quantification could be stably stored at least 1 week at -80 °C. The ceramides and dihydroceramides in normal mice liver and small intestinal tissues analyzed by the developed method indicated that the detected 9 ceramide and 5 dihydroceramides levels were significantly different, in which Cer d18:1/16:0, Cer d18:1/22:0, Cer d18:1/24:1, Cer d18:1/24:0 and dHCer d18:0/24:1 are the main components in the liver, whereas Cer d18:1/16:0 and dHCer d18:0/16:0 accounts for the majority of proportion in the intestinal tissues. CONCLUSION: A simple and rapid method for the quantification of 11 ceramides and 6 dihydroceramides in the animal tissues was developed and applied. The compositions of ceramides in two tissues suggested that the compositional features should to be considered when exploring the biomarkers or molecular mechanisms.

Random Lasing from Label-Free Living Cells for Rapid Cytometry of Apoptosis.

A random laser carrying the scattering information on a biological host is a promising tool for the characterization of biophysical properties. In this work, random lasing from label-free living cells is proposed to achieve rapid cytometry of apoptosis. Random lasing is achieved by adding biocompatible gain medium to a confocal dish containing cells under optically pumped conditions. The random lasing characteristics are distinct at different stages of cell apoptosis after drug treatment. By analyzing the power Fourier transform results of the random lasing spectra, the percentage of apoptotic cells could be distinguished within two seconds, which is more than an order of magnitude faster than traditional flow cytometry. These results provide a label-free approach for rapid cytometry of apoptosis, which is advantageous for further research of random lasers in the biological field.

Synergistic Modulation by Halogens and Pyridine Crossing the Blood-Brain Barrier for In Situ Visualization of Thiol Flux in the Epileptic Brain.

Epilepsy is a nervous system disease, and seizures are closely related to oxidative stress. Thiols, as the main antioxidant in an organism, play a key role in regulating the redox balance and defending from oxidative stress. As a result of the complexity of the brain structure, there is still a lack of suitable in situ detection methods of thiols to reveal the relationship between epilepsy and thiol level fluctuations. Therefore, by combining picolinate as the new recognition site for thiols, parallel synthesis, and the fluorescence rapid screening method, DCI-Br-3 was developed as a rapid, highly sensitive, and selective probe to monitor thiols in vitro and in vivo. It is worth noting that DCI-Br-3 effectively crossed the blood-brain barrier (BBB) to reveal the negative relationship between the level of thiols and the occurrence of epilepsy and may further provide important information for the prevention and treatment of thiol-related neurological diseases.

Dynamic manipulation of WGM lasing by tailoring the coupling strength.

Miniaturized lasing with dynamic manipulation is critical to the performance of compact and versatile photonic devices. However, it is still a challenge to manipulate the whispering gallery mode lasing modes dynamically. Here, we design the quasi-three-dimensional coupled cavity by a micromanipulation technique. The coupled cavity consists of two intersection polymer microfibers. The mode selection mechanism is demonstrated experimentally and theoretically in the coupled microfiber cavity. Dynamic manipulation from multiple modes to single-mode lasing is achieved by controlling the coupling strength, which can be quantitatively controlled by changing the coupling angle or the coupling distance. Our work provides a flexible alternative for the lasing mode modulation in the on-chip photonic integration.

Simultaneous and rapid detection of polychlorinated phenols in water samples by surface-enhanced Raman spectroscopy combined with principal component analysis.

In this work, a simple, high-throughput, and sensitive analytical method based on surface-enhanced Raman spectroscopy (SERS) and principal component analysis (PCA) was fabricated for simultaneous and rapid determination of three polychlorinated phenols (PCPs) including 2,4-dichlorophenol (2,4-DCP), 2,4,5-trichlorophenol (2,4,5-TCP), and 2,3,4,6-tetrachlorophenol (2,3,4,6-TeCP). The aggregated Ag nanoparticles (AgNPs) induced by inorganic salt ions were used as sensitive SERS substrate, and the electromagnetic field distribution of AgNPs with different distances was simulated by finite difference time domain (FDTD) to verify the theory feasibility. The high throughput and rapid detection can be achieved by commercial 96-pore plate. Under the optimum conditions, the linear relationship between the Raman intensity and the concentrations of PCPs was established with satisfied correlation coefficient. The limits of detection (LOD) for 2,4-DCP, 2,4,5-TCP, and 2,3,4,6-TeCP are 0.27 mg L-1, 0.09 mg L-1, and 0.10 mg L-1 by rules of 3σ, respectively. The simultaneous quantitative analysis can be achieved thanks to the independent Raman characteristic peaks of three PCPs. Afterwards, the PCA method was used to eliminate the limitations of overlapping of characteristic Raman peaks in structural analogues of 2,4-DCP, 2,4,5-TCP, and 2,3,4,6-TeCP. The recovery experiments including single PCPs and mixed PCP samples show satisfied recoveries ranging from 85.0 to 113.9% and 80.4 to 114.0% with RSDs in range of 0.4-9.5% and 1.1-10.7%, respectively. The proposed method shows great potentials in rapid, high-throughput, and sensitive monitoring of the contaminants in water and pesticide samples with similar structure. Here, we introduced aggregated Ag nanoparticles (AgNPs) induced by inorganic salt ion for simultaneous, rapid, and sensitive determination of polychlorinated phenols (PCPs) including 2,4-dichlorophenol (2,4-DCP), 2,4,5-trichlorophenol (2,4,5-TCP), and 2,3,4,6-tetrachlorophenol (2,3,4,6-TeCP) by surface-enhanced Raman spectroscopy (SERS) combined with principal component analysis (PCA). The AgNPs induced by inorganic salt ions were used as sensitive SERS substrate, and the electromagnetic field distribution of AgNPs with different distances was simulated by finite difference time domain (FDTD) to verify the theory feasibility. The PCA method was used to eliminate the limitations of overlapping of characteristic Raman peaks in structural analogues of 2,4-DCP, 2,4,5-TCP, and 2,3,4,6-TeCP. The proposed method shows great potentials in rapid, high-throughput, and sensitive monitoring of the contaminants in water and pesticide samples with similar structure.

Development of a model to predict recurrence after bronchial artery embolization for non-cancer related hemoptysis.

BACKGROUND: Relapse after effective bronchial arterial embolization (BAE) for controlling hemoptysis is not uncommon. Studies reported diverse predictors of recurrence. However, a model to assess the probability of recurrence in non-cancer related hemoptysis patients after BAE has not been reported. This study was to develop a model to predict recurrence after BAE for non-cancer related hemoptysis. METHODS: The study cohort included 487 patients who underwent BAE for non-cancer-related hemoptysis between January 2015 and December 2019. We derived the model's variables from univariate and multivariate Cox regression analyses. The model presented as a nomogram scaled by the proportional regression coefficient of each predictor. Model performance was assessed with respect to discrimination and calibration. RESULTS: One-month and 1-, 2-, 3- and 5-year recurrence-free rates were 94.5%, 88.0%, 81.4%, 76.2% and 73.8%, respectively. Risk factors for recurrence were underlying lung diseases and the presence of systemic arterial-pulmonary circulation shunts. This risk prediction model with two risk factors provided good discrimination (area under curve, 0.69; 95% confidence interval, 0.62-0.76), and lower prediction error (integrated Brier score, 0.143). CONCLUSION: The proposed model based on routinely available clinical and imaging features demonstrates good performance for predicting recurrence of non-cancer-related hemoptysis after BAE. The model may assist clinicians in identifying higher-risk patients to improve the long-term efficacy of BAE.

Low-cost biosensors based on a plasmonic random laser on fiber facet.

Low-cost and miniaturized biosensors are key factors leading to the possibility of portable and integrated biomedical system, which play an important role in clinical medicine and life sciences. Random lasers with simple structures provide opportunities for detecting biomolecules. Here, low-cost biosensors on fiber facet for label-free detecting biomolecules are demonstrated based on a plasmonic random laser. The random laser is achieved resorting to a self-assembled plasmonic scattering structure of Ag nanoparticles and polymer film on fiber facet. Refractive index sensitivity and near-surface sensitivity of the biosensor are systematically studied. Furthermore, the biosensor is used to detect IgG through specific binding to protein A, exhibiting the detecting limit of 0.68 nM. It is believed that this work may promote the applications of a plasmonic random laser bio-probe in portable or integrated medical diagnostic platforms, and provide fundamental understanding for the life science.

Thin-layer chromatography combined with surface-enhanced Raman scattering for rapid detection of benzidine and 4-aminobiphenyl in migration from food contact materials based on gold nanoparticle doped metal-organic framework.

In this work, a rapid and sensitive thin-layer chromatography combined with surface-enhanced Raman spectroscopy method was established for rapid detection of benzidine and 4-aminobiphenyl in migration from food contact materials based on Au nanoparticle doped metal-organic framework. Benzidine and 4-aminobiphenyl were firstly separated by thin-layer chromatography to solve the limitation of their overlapping Raman peaks. Then the target molecules were monitored by adding AuNPs/MIL-101(Cr) on the sample spots. Under the optimum conditions, the concentration of benzidine and 4-aminobiphenyl can be quantitatively measured in the range of 2.0-20.0 and1.0-15.0 µg/L, respectively with good linear relationship, and the limits of detection were 0.21 and 0.23 µg/L, respectively. Furthermore, the developed method was applied to analyze benzidine and 4-aminobiphenyl in migration of different food contact materials. The recoveries of benzidine and 4-aminobiphenyl for migration of food contact materials, including paper cups, polypropylene food containers, and polyethylene glycol terephthalate bottles, were 80.6-116.0 and 80.7-118% with relative standard deviations of 1.1-9.1 and 3.1-9.9%, respectively. Surface-enhanced Raman scattering detection was performed conveniently in the on-plate mode without additional elution process. The method shows great potential in rapid monitoring of hazardous substances with overlapping characteristic Raman peaks in food contact materials.

Food withdrawal alters the gut microbiota and metabolome in mice.

Food withdrawal as a health-enhancing measure has beneficial effects on aging, disease prevention, and treatment. However, the cellular and molecular mechanisms involving gut microbial changes and metabolic consequences resulting from food withdrawal have yet to be elucidated. In this study, we subjected lean and obese mice to a dietary intervention that consisted of a 4-d complete food withdrawal and an 8-d 50% food withdrawal, and we studied changes in cecal microbiome and host serum metabolome. The abundance of potentially pathogenic Proteobacteria was decreased and Akkermansia muciniphila was elevated by food withdrawal in mice fed a high-fat diet (HFD). Meanwhile, food withdrawal decreased the abundance of metabolites in branched chain amino acid, lipid, and free fatty acid metabolisms in host serum, more so in HFD mice than in normal mice. Microbial predicted function also showed that food withdrawal decreased the abundance of microbes associated with predicted diseases in the HFD group but not in the normal chow group. Correlation between the microbiome data and metabolomics data revealed a strong association between gut microbial and host metabolic changes in response to food withdrawal. In summary, our results showed that food withdrawal was safer and more metabolically beneficial to HFD-induced obese mice than to normal lean mice, and the beneficial effects were primarily derived from the changes in gut microbiota, which were closely associated with the host metabolome.-Zheng, X., Zhou, K., Zhang, Y., Han, X., Zhao, A., Liu, J., Qu, C., Ge, K., Huang, F., Hernandez, B., Yu, H., Panee, J., Chen, T., Jia, W., Jia, W. Food withdrawal alters the gut microbiota and metabolome in mice.

Near-infrared-emitting persistent luminescent nanoparticles modified with gold nanorods as multifunctional probes for detection of arsenic(III).

Near infrared (NIR)-emitting persistent luminescent nanoparticles (PLNPs) have advantages such as long afterglow, high photostability and deep tissue spectral penetration. A NIR-emitting inner filter effect (IFE) probe for arsenic(III) is described here. It is composed of polyethyleneimine-coated PLNPs and gold nanorods (AuNPs) coated with dithiothreitol. The probe can detect arsenic(III) (= arsenite) selectively even in the presence of interfering substances. The PLNPs and AuNPs were prepared by a hydrothermal method combined with high-temperature calcination and seed-mediated growth mechanism, respectively. The PLNPs show excellent NIR luminescence (with excitation/emission peaks at 254/695 nm) and long afterglow (lifetime >1200 s). The use of polyethyleneimine improves water solubility and provides positive surface charges for the PLNPs. On exposure to arsenite ions, the luminescence of the probe at 695 nm is restored. Under the optimum conditions, the method can detect As(III) in the 0.067 to 13.4 µmol·L-1 concentration range with good linear relationship (R2 = 0.99734), and the detection limit (at S/N = 3) is 55 nmol·L-1. The precision of this method was demonstrated by 11 replicate detections of 2 µmol·L-1 As(III), and the relative standard deviations (RSD) is 2.1%. The practicality was evaluated by the analyses of real water samples and recoveries for the water samples spiked with 2, 5 and 10 µmol·L-1 of As(III) were 89.8%-100.1% with RSDs ranging from 3.0-5.7%. Graphical abstract A near infrared-emitting inner filter effect (IFE) inhibition probe is presented. It is based on the combination of polyethyleneimine (PEI)-coated NIR-emitting persistent luminescent nanoparticles (type Zn1.25Ga1.5Ge0.25O4: Cr3+, ZGGO) (PLNPs-PEI) with dithiothreitol (DTT)-coated gold nanorods (AuNPs) (DTT-AuNPs) to detect arsenite.

A Colorimetric Probe Based on Functionalized Gold Nanorods for Sensitive and Selective Detection of As(III) Ions.

A colorimetric probe for determination of As(III) ions in aqueous solutions on basis of localized surface plasmon resonance (LSPR) was synthesized. The dithiothreitol molecules with two end thiols covalently combined with Au Nanorods (AuNRs) with an aspect ratio of 2.9 by Au-S bond to form dithiothreitol coated Au Nanorods (DTT-AuNRs), acting as colorimetric probe for the determination of As(III) ions. With the adding of As(III) ions, the AuNRs will be aggregated and leading the longitudinal SPR absorption band of DTT-AuNRs decrease due to the As(III) ions can bind with three DTT molecules through an As-S linkage. The potential factors affect the response of DTT-AuNRs to As(III) ions including the concentration of DTT, pH values of DTT-AuNRs, reaction time and NaCl concentration were optimized. Under optimum assay conditions, the DTT-AuNRs colorimetric probe has high sensitivity towards As(III) ions with low detection limit of 38 nM by rules of 3σ/k and excellent linear range of 0.13⁻10.01 µM. The developed colorimetric probe shows high selectivity for As(III) ions sensing and has applied to determine of As(III) in environmental water samples with quantitative spike-recoveries range from 95.2% to 100.4% with low relative standard deviation of less than 4.4% (n = 3).

Monodisperse, Self-Activated Luminescent, and Mesoporous Silica Nanospheres for Drug Delivery.

Monodisperse mesoporous silica nanospheres with novel self-activated luminescence have been fabricated by a modified templating sol­gel method followed by heat treatment, without introducing any rare earth or transition metal ions as activators. The SEM, TEM, and N2 adsorption/desorption isotherms results show that the as-obtained mesoporous silica nanospheres exhibit well-defined morphology, good dispersion, high specific surface area and pore volume. MTT assay indicates that the sample exhibits no obvious cytotoxicity against the A549, HeLa, and MCF-7 cells, which make it suitable to be utilized as a drug carrier. Under ultraviolet excitation, the sample exhibits an intense blue emission. Interestingly, the photoluminescence intensity of the IBU drug loaded system increases with the increase of cumulatively released IBU. Due to the relationship between the luminescence properties and drug release behavior, the as-obtained luminescent drug carrier may be potential as a probe for monitoring or detecting the drug release process.

Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis.

Dysregulated bile acids (BAs) are closely associated with liver diseases and attributed to altered gut microbiota. Here, we show that the intrahepatic retention of hydrophobic BAs including deoxycholate (DCA), taurocholate (TCA), taurochenodeoxycholate (TCDCA), and taurolithocholate (TLCA) were substantially increased in a streptozotocin and high fat diet (HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mouse model. Additionally chronic HFD-fed mice spontaneously developed liver tumors with significantly increased hepatic BA levels. Enhancing intestinal excretion of hydrophobic BAs in the NASH-HCC model mice by a 2% cholestyramine feeding significantly prevented HCC development. The gut microbiota alterations were closely correlated with altered BA levels in liver and feces. HFD-induced inflammation inhibited key BA transporters, resulting in sustained increases in intrahepatic BA concentrations. Our study also showed a significantly increased cell proliferation in BA treated normal human hepatic cell lines and a down-regulated expression of tumor suppressor gene CEBPα in TCDCA treated HepG2 cell line, suggesting that several hydrophobic BAs may collaboratively promote liver carcinogenesis.

Bone-Targeted Mesoporous Silica Nanocarrier Anchored by Zoledronate for Cancer Bone Metastasis.

Once bone metastasis occurs, the chances of survival and quality of life for cancer patients decrease significantly. With the development of nanomedicine, nanocarriers loading bisphosphonates have been built to prevent cancer metastasis based on their enhanced permeability and retention (EPR) effects; however, as a passive mechanism, the EPR effects cannot apply to the metastatic sites because of their lack of leaky vasculature. In this study, we fabricated 40 nm-sized mesoporous silica nanoparticles (MSNs) anchored by zoledronic acid (ZOL) for targeting bone sites and delivered the antitumor drug doxorubicin (DOX) in a spatiotemporally controlled manner. The DOX loading and release behaviors, bone-targeting ability, cellular uptake and its mechanisms, subcellular localization, cytotoxicity, and the antimigration effect of this drug delivery system (DDS) were investigated. The results indicated that MSNs-ZOL had better bone-targeting ability compared with that of the nontargeted MSNs. The maximum loading capacity of DOX into MSNs and MSNs-ZOL was about 1671 and 1547 mg/g, with a loading efficiency of 83.56 and 77.34%, respectively. DOX@MSNs-ZOL had obvious pH-sensitive DOX release behavior. DOX@MSNs-ZOL entered into cells through an ATP-dependent pathway and then localized in the lysosome to achieve effective intracellular DOX release. The antitumor results indicated that DOX@MSNs-ZOL exhibited the best cytotoxicity against A549 cells and significantly decreased cell migration in vitro. This DDS is promising for the treatment of cancer bone metastasis in the future.