Biomimetic Lubrication and Surface Interactions of Dopamine-Assisted Zwitterionic Polyelectrolyte Coatings.

A bioinspired zwitterionic polyelectrolyte coating with excellent hydration ability has been regarded as a promising lubricating candidate for modifying artificial joint cartilage surface. In physiological fluids, the ubiquitous proteins play an important role in achieving outstanding boundary lubrication; however, a comprehensive understanding of the hydration lubrication between polyelectrolyte coatings and proteins still remains unclear. In this work, a facile fabrication of ultrasmooth polyelectrolyte coatings was developed via codeposition of synthesized poly(dopamine methacrylamide- co-2-methacryloyloxyethyl phosphorylcholine) (P(DMA- co-MPC)) and dopamine (DA) in a mild condition. Upon optimization of the feeding ratio of P(DMA- co-MPC) and DA, the as-fabricated PDA/P(DMA- co-MPC) coatings exhibit excellent lubricating properties when sliding with each other (friction coefficient µ = 0.036 ± 0.002, ∼2.8 MPa), as well as sliding with a model protein (bovine serum albumin (BSA)) layer (µ = 0.041 ± 0.005, ∼4.8 MPa) in phosphate-buffered saline (PBS, pH 7.4). Intriguingly, the lubrication in both systems shows Amontons-like behaviors: the friction is directly proportional to the applied load but independent of the shear velocity. Moreover, the PDA/P(DMA- co-MPC) coatings could resist the protein fouling (i.e., BSA) in PBS, which is crucial to prevent the surfaces from being contaminated when applied in biological media, thus maintaining their lubricating properties. Our results provide a versatile approach for facilely fabricating polyelectrolyte coatings with superior lubrication properties to both polyelectrolyte coatings and protein surfaces, with useful implications into the development of novel lubricating coatings for bioengineering applications (e.g., artificial joints).

Molecular imaging of angiogenesis to delineate the tumor margins in glioma rat model with endoglin-targeted paramagnetic liposomes using 3T MRI.

PURPOSE: To evaluate the use of endoglin-targeted paramagnetic liposomes in delineating the glioma margins using magnetic resonance (MR) angiogenesis imaging in a rat model. MATERIALS AND METHODS: Four liposome preparations, including nontargeted paramagnetic liposomes (Gd-SLs), isotype control IgG-coupled paramagnetic liposomes (IgG-Gd-SLs), endoglin monoclonal antibody coupled paramagnetic liposomes (MAb-Gd-SLs), and biotinylated antibodies (Bio-MAb)/streptavidin-coupled paramagnetic liposomes (SAv-Gd-SLs) for two-step pretargeting imaging, were formulated. All animal experiments were carried out with the approval of the Shanghai Animal Care. C6 glioma-bearing Sprague-Dawley rats were intravenously injected with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) or the previously mentioned liposomes (n = 5) and imaged with MR. T1 -weighted MRI was performed before and dynamically repeated after different contrast agents were injected. The enhancement features of the tumors were compared. RESULTS: The signal enhancement of the tumor in the two-step pretargeting group increased by 117.9 ± 5.3% at the periphery and 109.2 ± 3.5% in the center (P = 0.032) at the 8-hour timepoint after SAv-Gd-SLs injection. Ring-like enhancement margins were demonstrated at the periphery of the tumor in the two-step targeted group. The specificity of the targeted liposomes was supported by the competitive study. The signal of peak enhancement using MAb-Gd-SLs was 59% less than that of the two-step group and only slightly higher than the non-targeted groups. CONCLUSION: The two-step endoglin-targeted imaging using biotin-streptavidin interaction was demonstrated to induce intense enhancement of the tumor periphery, which implies that this advanced MR molecular contrast agent may be suitable for accurately delineating glioma tumor margins. J. Magn. Reson. Imaging 2015;41:1056-1064. © 2014 Wiley Periodicals, Inc.

In situ grown bacterial cellulose/MoS2 composites for multi-contaminant wastewater treatment and bacteria inactivation.

For the purpose of developing multifunctional water purification materials capable of degrading organic pollutants while simultaneously inactivating microorganisms from contaminated wastewater streams, we report here a facile and eco-friendly method to immobilize molybdenum disulfide into bacterial cellulose via a one-step in-situ biosynthetic method. The resultant nanocomposite, termed BC/MoS2, was shown to possess a photocatalytic activity capable of generating •OH from H2O2, while also exhibiting photodynamic/photothermal mechanisms, the combination of which exhibits synergistic activity for the degradation of pollutants as well as for bacterial inactivation. In the presence of H2O2, the BC/MoS2 nanocomposite exhibited excellent antibacterial efficacy upwards of 99.9999% (6 log units) for the photoinactivation of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus upon infrared (IR) lamp illumination (100 W, 760 nm ≤ λ ≤ 5000 nm, 15 cm vertical distance; 5 min). Mechanistic studies revealed synergistic pathogen inactivation resulting from the combination of photocatalytically generated •OH and hyperthermia induced by the photothermal conversion of the near-IR light. In addition, the BC/MoS2 nanocomposite also showed excellent photodegradation activity for common aqueous contaminants in the presence of H2O2, including malachite green (a textile dye), catechol violet (a phenol) and formaldehyde. Taken together, our findings demonstrate that sustainable materials such as BC/MoS2 have potential applications in wastewater treatment and microorganism disinfection.

LncKCNQ1OT1 Promotes the Odontoblastic Differentiation of Dental Pulp Stem Cells via Regulating hsa-miR-153-3p/RUNX2 Axis.

This study aimed to explore the role of LncKCNQ1OT1/hsa-miR-153-3p/RUNX2 in the odontoblastic differentiation of human dental pulp stem cells (DPSCs) and its possible mechanism. The expression of LncKCNQ1OT1, hsa-miR-153-3p, and RUNX2 in the odontoblastic differentiation was detected by qRT-PCR. Interaction between LncKCNQ1OT1 and hsa-miR-153-3p and interaction between hsa-miR-153-3p and RUNX2 were detected by dual-luciferase assay. The cell viability of DPSCs was detected by CCK-8, and the effect of LncKCNQ1OT1 and hsa-miR-153-3p on the odontoblastic differentiation of DPSCs was observed by alizarin red staining, alkaline phosphatase (ALP) activity assay, and Western blot for RUNX2, DSPP, and DMP-1. The results showed, during odontoblastic differentiation of DPSCs, the expression of LncKCNQ1OT1 increased, hsa-miR-153-3p expression decreased, and RUNX2 expression increased. Dual-luciferase assay showed that LncKCNQ1OT1 sponges hsa-miR-153-3p and hsa-miR-153-3p targets on RUNX2. After LncKCNQ1OT1 and hsa-miR-153-3p expressions of DPSCs were changed, the cell viability was not notably changed, but the odontoblastic differentiation was notably changed, which was confirmed with Alizarin Red staining, ALP activity, and Western blot for RUNX2, DSPP, and DMP-1. The results indicate that LncKCNQ1OT1 promotes the odontoblastic differentiation of DPSCs via regulating hsa-miR-153-3p/RUNX2 axis, which may provide a therapeutic clue for odontogenesis.

Aging simulation of thin-film plastics in different environments to examine the formation of microplastic.

Microplastics have received considerable attention in recent years. Understanding the aging mechanism of plastics in different environments (land, fresh water, estuary, and ocean) is critical to control the microplastic formation. Therefore, the aging process of plastics, including polyethylene (PE) and polypropylene (PP), in different environments was simulated by analyzing their physical and chemical structures by using the Raman spectroscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy techniques. After 23 weeks, micro-scale microplastics (size less than 100 µm) could be extracted from the plastic surface through smashing waves in all fresh water and seawater samples. However, complete fragmentation was observed only in the case of thin-film plastics (TFPs, thickness of approximately 10 µm). This phenomenon indicated that TFPs disintegrated to microplastics more easily in the water system than on land, and the water flow notably affected the production of micro-scale particles. Furthermore, ultraviolet radiation affected the chemical structure of plastics through a two-stage process in all environments. In the initial stage, chemical aging occurred in the amorphous regions of both PE and PP, leading to the generation of newly functional groups such as C=O at 1717 cm-1, and a reduced contact angle. In the later stage, PE exhibited additional crystals and increased contact angles, whereas PP demonstrated the tendency of producing oxygen-containing functional groups that could reduce the crystallinity. In addition, several inorganic salts (such as sulfate and phosphorus) in seawater likely combined with C-H-type stretches, thereby promoting the chemical aging of plastics.

Applying Pb2+ to probe the dissolution of carbonated hydroxylapatite by Enterobacter sp.: A new insight into the bioerosion of tooth mineral.

Dental caries is one of the most common disorders in dentistry. Typically, it is caused by the dissolution of the tooth mineral due to cariogenic organisms. Bioapatite is vulnerable to acid-etching ascribed to a variety of substitutions. This study applied Pb2+ cations to probe the dissolution of synthetic carbonated hydroxylapatite (CHAp) in the acidic environment induced by Enterobacter sp. It indicated a decreasing tendency of crystallite size (from ∼400 nm to 10-20 nm) during gradual incorporation of carbonate (from 2.5 to 13.8 wt %). Meanwhile, the shape of CHAp crystals was transformed from elongated to plate-like. Addition of Enterobacter sp. enhanced P release from CHAp (especially for the CHAp with ∼8 wt % CO3 ) around 10 times. Moreover, the bacterium provided a moderately acidic environment to cause more formation of stable pyromorphite over other Pb-minerals, for example, Pb3 (PO4 )2 , and PbCO3 . Then, transmission electron microscopy-energy dispersive X-Ray spectroscopy mapping successfully confirmed the Pb labeling on the newly formed phosphate mineral as Pb (with high-atomic weight) has strong signal under electron microscopy. This study therefore elucidated that Pb labeling has a bright future to explore the degradation of tooth mineral by microorganisms, as well as to evaluate the resistance of calcium phosphate dental restorative materials.

Harnessing X-Ray Energy-Dependent Attenuation of Bismuth-Based Nanoprobes for Accurate Diagnosis of Liver Fibrosis.

Timely detection of liver fibrosis by X-ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X-ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X-ray attenuation characteristics of the scanned matter. Herein, an X-ray energy-dependent attenuation strategy originated from bismuth (Bi)-based nanoprobes (BiF3 @PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3 @PDA@HA can exhibit characteristic attenuation depending on different levels of X-ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3 @PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3 @PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy-dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging-based disease diagnosis.

Development of nimesulide amorphous solid dispersions via supercritical anti-solvent process for dissolution enhancement.

Formulating amorphous solid dispersions (ASDs) is one of the most promising strategies to overcome solubility limitations in drug development. In this work, development of nimesulide (NIM) ASDs via supercritical anti-solvent (SAS) process was proposed, where the mixtures of dichloromethane (DCM) and methanol (MeOH) were selected as the liquid solvent, and the mixtures of hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) were the dispersing materials. The effects of NIM/HPMC/PVP (w/w/w) ratio and DCM/MeOH (v/v) ratio on particle solid-state properties were investigated to identify successful operating conditions. NIM-ASDs powders were formed by well separated spherical microparticles, where NIM crystals had transformed into amorphous state completely; the production yield was 93.6 ± 1.14%; and the reproducibility was very high. For NIM-ASDs, intermolecular interactions between NIM and dispersing materials were formed; the residual solvent was far below the ICH limit; and the chemical structure of NIM did not be degraded or disrupted. Moreover, NIM-ASDs increased the NIM solubility in PBS (pH=6.8) more than 5-folds; the dissolution of NIM from NIM-ASDs granules was faster and more complete than that from commercial Aulin® granules in PBS (pH=6.8). Also, NIM-ASDs well hindered the aging in the recrystallization of amorphous NIM during 12-month sealed storage. Overall, development of NIM-ASDs via SAS process presents an opportunity that as a modified product to increase the efficacy of NIM.

Artificial anaerobic cell dormancy for tumor gaseous microenvironment regulation therapy.

Oxygen is known as an irreplaceable gas in the lives of most eukaryotic cells, yet researchers underestimate its importance, as in the case in many studies of tumors. The variable oxygen content of malignant solid tumors increases the difficulty of treatment. Thus, it could be reasonably inferred that the tumor oxygen microenvironment, if efficiently and completely regulated, could bring certain changes to existing therapies. Based on this speculation, an acid-responsive, oxygen-scavenging and anaerobic-sensitizing nanoparticle was designed to regulate the oxygen level of solid tumor by creating an artificial anaerobic environment in our study. The Mg2Si core, which acted as a deoxygenating agent, was able to consume tumor oxygen and cause cell dormancy, while the incorporated hydrophobic tirapazamin (TPZ) helped to kill the now-dormant tumor cells. This simple and nontoxic nanoparticle achieved controllable factitious anaerobic circumstance in solid tumor for the first time, displaying the considerable potential and promising application of tumor gaseous microenvironment regulation therapy.

PEGylated NaHoF4 nanoparticles as contrast agents for both X-ray computed tomography and ultra-high field magnetic resonance imaging.

It is well-known that multimodal imaging can integrate the advantages of different imaging modalities by overcoming their individual limitations. As ultra-high field magnetic resonance imaging (MRI) will be inevitably used in future MRI/X-ray computed tomography (CT) scanner, it is highly expected to develop high-performance nano-contrast agents for ultra-high field MR and CT dual-modality imaging, which has not been reported yet. Moreover, specific behavior of nano-contrast agents for ultra-high field MRI is a challenging work and still remains unknown. Herein, a novel type of NaHoF4 nanoparticles (NPs) with varied particle sizes were synthesized and explored as high-performance dual-modality contrast agents for ultra-high field MR and CT imaging. The specific X-ray absorption and MR relaxivity enhancements with varied nanoparticle diameters (3 nm, 7 nm, 13 nm and 29 nm) under different magnetic field (1.5/3.0/7.0 T) are investigated. Based on experimental results and theoretical analysis, the Curie and dipolar relaxation mechanisms of NaHoF4 NPs are firstly separated. Our results will greatly promote the future medical translational development of the NaHoF4 nano-contrast agents for ultra-high field MR/CT dual-modality imaging applications.