Heteroatom-engineered multicolor lignin carbon dots enabling bimodal fluorescent off-on detection of metal-ions and glutathione.

Carbon dots (CDs) have emerged as a promising subclass of optical nanomaterials with versatile functions in multimodal biosensing. Howbeit the rapid, reliable and reproducible fabrication of multicolor CDs from renewable lignin with unique groups (e.g., -OCH3, -OH and -COOH) and alterable moieties (e.g., ß-O-4, phenylpropanoid structure) remains challenging due to difficult-to-control molecular behavior. Herein we proposed a scalable acid-reagent strategy to engineer a family of heteroatom-doped multicolor lignin carbon dots (LCDs) that are functioned as the bimodal fluorescent off-on sensing of metal-ions and glutathione (GSH). Benefiting from the modifiable photophysical structure via heteroatom-doping (N, S, W, P and B), the multicolor LCDs (blue, green and yellow) with a controllable size distribution of 2.06-2.22 nm deliver the sensing competences to fluorometric probing the distinctive metal-ion systems (Fe3+, Al3+ and Cu2+) under a broad response interval (0-500 µM) with excellent sensitivity and limit of detection (LOD, 0.45-3.90 µM). Meanwhile, we found that the addition of GSH can efficiently restore the fluorescence of LCDs by forming a stable Fe3+-GSH complex with a LOD of 0.97 µM. This work not only sheds light on evolving lignin macromolecular interactions with tunable luminescent properties, but also provides a facile approach to synthesize multicolor CDs with advanced functionalities.

PD-1 engineered cytomembrane cloaked molybdenum nitride for synergistic photothermal and enhanced immunotherapy of breast cancer.

Incomplete tumor ablation and subsequent tumor metastasis usually occur during photothermal anti-tumor processes. The combination of photothermal and immunotherapy has proven to be a promising method to conquer technical challenges. Inhibiting the programmed death ligand-1 (PD-L1)/programmed cell death protein 1 (PD-1) immune pathway represents one of the most successful immunotherapy strategies. Whereas, the PD-L1 expression level significantly differs, leading to a relatively low response rate to the immune checkpoint blockade (ICB) approaches. Therefore, improving the expression level of PD-L1 becomes one potential method to enhance the response rate. Herein, NIH 3T3 cells were educated to steadily express PD-1 protein. Furthermore, the synthesized molybdenum nitride was then coated with PD-1 protein-modified cytomembrane, which endows it with immune checkpoint blocking capability. Moreover, under the irradiation of near-infrared light, the local mild heat released from the molybdenum nitride causes the apoptosis of tumor cells. More importantly, the elevated temperature simultaneously helps elevate the expression level of PD-L1, further enhancing the response rate of ICB. Finally, the PD-1 cytomembrane coatings interact with the upregulated PD-L1, leading to the activation of the immune system. In summary, we confirmed that the PD-1 protein-coated molybdenum nitride could synergistically ablate tumors and avoid metastasis.

Resveratrol-loaded titania nanotube coatings promote osteogenesis and inhibit inflammation through reducing the reactive oxygen species production via regulation of NF-κB signaling pathway.

Although titanium and its alloys are widely used in bone surgeries, the implantation failures caused by sterile inflammation still occur. The excessive reactive oxygen species (ROS) in the peri-implant region are considered to cause inflammation and impede the osseointegration of titanium implants. In this study, a coating of resveratrol-loaded titania nanotube (TNT-Res) for eliminating ROS was fabricated on titanium surface through electrochemical anodization and following surface adsorption of resveratrol. The resveratrol concentration of released from TNT-Res coating was controlled by modulating the loading amount. The ROS production in macrophage cell lineage RAW 264.7 and bone mesenchymal stem cells (BMSCs) were significantly decreased when cultured on TNT-Res coatings. The pro-inflammatory factors, including tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß), and NO produced by RAW 264.7 cells were reduced when cells were cultured on TNT-Res coatings. These results proved that the TNT-Res coating can effectively eliminate ROS and inhibit inflammation. Moreover, the osteogenic indicators, including alkaline phosphatase (ALP) production, extracellular calcium deposition, and osteogenesis-related gene expression, including collagen І (Col-І), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (Runx2), were significantly promoted for TNT-Res groups, which demonstrated that the TNT-Res coating can enhance the osteogenic differentiation of BMSCs. Additionally, the phosphorylation of nuclear factor κ-B (NF-κB) were down-regulated both in RAW 264.7 cells and BMSCs, which indicated that the TNT-Res coating could inhibit inflammation and promote osteogenesis by inhibiting the activation of NF-κB signaling pathway. The TNT-Res coating could be an effective implant surface for improving osseointegration ability of titanium implants.

Lithiated NiCo2O4 Nanorods Anchored on 3D Nickel Foam Enable Homogeneous Li Plating/Stripping for High-Power Dendrite-Free Lithium Metal Anode.

Lithium (Li) metal is one of the promising anode materials in the next-generation high-energy batteries, but Li dendrite growth and a big volume change during cycling result in low Coulombic efficiency (CE), short lifespan, and safety hazards, thereby impeding practical implementation of Li in rechargeable batteries. Herein, we report a highly stable and dendrite-free Li metal anode based on a three-dimensional (3D) conductive and lithiophilic scaffold comprising lithiated NiCo2O4 nanorods grown on nickel foam (LNCO/Ni). The nanorods grown on 3D Ni foam with a large surface area effectively reduce the averaged electrical current in the electrode, and the conformal Li2O coating produced in situ on the lithiated NiCo2O4 nanorods provides the surface lithiophilicity enabling stable Li plating/stripping without Li dendrite growth even at a high current density of 5 mA cm-2. The LNCO/Ni-Li anode shows a low voltage hysteresis of 16 mV, high CE of 98.7%, and stable cycling without obvious voltage fluctuation for over 500 cycles (1000 h) at a current density of 1 mA cm-2. Specifically, for a scalable Li loading of 20 mA h cm-2 on LNCO/Ni, no growth of Li dendrite and electrode thickness fluctuations are observed. The full cell consisting of the LNCO/Ni-Li anode and the LiFePO4 cathode exhibits a high rate capability and CE as high as 99.6% for more than 160 cycles. Our study reveals a new strategy to develop stable Li-metal anodes for high-energy batteries.

Long-lasting bactericidal activity through selective physical puncture and controlled ions release of polydopamine and silver nanoparticles-loaded TiO2 nanorods in vitro and in vivo.

Background: Titanium (Ti) implant-associated infection, which is mostly caused by bacterial adhesion and biofilm formation, may result in implant failure and secondary surgery. Thus it is an urgent issue to prevent bacterial infections at the earliest step. Purpose: To develop a novel surface strategy of polydopamine (PDA) and silver (Ag) nanoparticle-loaded TiO2 nanorods (NRDs) coatings on Ti alloy. Materials and methods: Ag-TiO2@PDA NRDs was fabricated on Ti alloy by hydrothermal synthesis. The antibacterial activity of Ag-TiO2@PDA NRDs against Escherichia coli and methicillin-resistant Staphylococcus aureus were tested by FE-SEM, Live/Dead staining, zone of inhibition, bacteria counting method and protein leakage analysis in vitro. In addition, an implant infection model was conducted and the samples were tested by X-ray, Micro-CT and histological analysis in vivo. Besides, cell morphology and cytotoxicity of Mouse calvarial cells (MC3T3-E1) were characterized by FE-SEM, immunofluorescence and CCK-8 test in vitro. Results: Our study successfully developed a new surface coating of Ag-TiO2@PDA NRDs. The selective physical puncture of bacteria and controlled release of Ag+ ions of Ag-TiO2@PDA NRDs achieved a long-lasting bactericidal ability and anti-biofilm activity with satisfied biocompatibility. Conclusion: This strategy may be promising for clinical applications to reduce the occurrence of infection in the implant surgeries.

Silver-loaded nanotubular structures enhanced bactericidal efficiency of antibiotics with synergistic effect in vitro and in vivo.

Antibiotic-resistant bacteria have become a major issue due to the long-term use and abuse of antibiotics in treatments in clinics. The combination therapy of antibiotics and silver (Ag) nanoparticles is an effective way of both enhancing the antibacterial effect and decreasing the usage of antibiotics. Although the method has been proved to be effective in vitro, no in vivo tests have been carried out at present. Herein, we described a combination therapy of local delivery of Ag and systemic antibiotics treatment in vitro in an infection model of rat. Ag nanoparticle-loaded TiO2 nanotube (NT) arrays (Ag-NTs) were fabricated on titanium implants for a customized release of Ag ion. The antibacterial properties of silver combined with antibiotics vancomycin, rifampin, gentamicin, and levofloxacin, respectively, were tested in vitro by minimum inhibitory concentration (MIC) assay, disk diffusion assay, and antibiofilm formation test. Enhanced antibacterial activity of combination therapy was observed for all the chosen bacterial strains, including gram-negative Escherichia coli (ATCC 25922), gram-positive Staphylococcus aureus (ATCC 25923), and methicillin-resistant Staphylococcus aureus (MRSA; ATCC 33591 and ATCC 43300). Moreover, after a relative short (3 weeks) combinational treatment, animal experiments in vivo further proved the synergistic antibacterial effect by X-ray and histological and immunohistochemical analyses. These results demonstrated that the combination of Ag nanoparticles and antibiotics significantly enhanced the antibacterial effect both in vitro and in vivo through the synergistic effect. The strategy is promising for clinical application to reduce the usage of antibiotics and shorten the administration time of implant-associated infection.

Long-lasting in vivo and in vitro antibacterial ability of nanostructured titania coating incorporated with silver nanoparticles.

Although titanium (Ti) implants are widely used clinically, implant-associated bacterial infection is still one of the most serious complications in orthopedic surgery. Long-term antibacterial properties and the ability to inhibit biofilm formation are highly desirable to prevent implant associated infection. In this study, a controllable amount of silver (Ag) nanoparticles was incorporated into titanium oxide; or titanium, nanotubes (TiO2 -NTs). The reliable release and long-term antibacterial function of Ag, in vivo and in vitro, and influence normal bone-implant integration from the Ag released from Ag-incorporated NTs in vivo have been studied to make them useable in clinical practice. In the current study, TiO2 -NTs loaded with Ag (NT-Ag) exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA, ATCC43300) in vitro for 30 days, and the ability to penetrate the protein layer well. In addition, X-ray examination and 2-[(18)F]-fiuoro-2-deoxy-D-glucose positron emission tomography indicates that NT-Ag show extremely long antibacterial activity in vivo in a rat model. Furthermore, histomorphometric analysis demonstrated that satisfactory bio-integration can be expected. Our results indicate that NT-Ag has both simultaneous antimicrobial and excellent bio-integration properties, make it a promising therapeutic material for orthopedic application.

Osteogenic activity and antibacterial effects on titanium surfaces modified with Zn-incorporated nanotube arrays.

Titanium implants having enhanced osteogenic activity and antibacterial property are highly desirable for the prevention of implant associated infection and promotion of osseointegration. In this study, coatings containing titania nanotubes (NTs) incorporated with zinc (NT-Zn) are produced on Ti implants by anodization and hydrothermal treatment in Zn containing solutions. The amount of incorporated Zn can be adjusted by varying the structural parameters such as the nanotube diameter and length as well as hydrothermal treatment time. The suitable NT-Zn coatings with good intrinsic antibacterial properties can prevent post-operation infection. Excellent osteogenesis inducing ability in the absence of extraneous osteogenic supplements is demonstrated and the ERK1/2 signaling is found to be involved. The NT-Zn structure which is simple, stable, and easy to produce and scale up has immense potential in bone implant applications.

The osteogenic activity of strontium loaded titania nanotube arrays on titanium substrates.

Development of biomedical titanium implants with high osteogenic ability for fast and good osseointegration under normal as well as osteoporotic conditions is hotly pursued. Strontium (Sr) loaded nanotubular structures (NT-Sr) that allow controlled and long-term Sr release are expected to yield favorable osteogenic effects and properties. NT-Sr structures with different tube diameters are fabricated by hydrothermal treatment of titania nanotubes formed at 10 and 40 V (NT10 and NT40). The loaded Sr amounts are regulated by the hydrothermal treatment time of 1 and 3 h (samples NT10-Sr1, NT10-Sr3, NT40-Sr1 and NT40-Sr3) in the Sr(OH)(2) solution. Long lasting and controllable Sr release is observed from the NT-Sr samples with no cytotoxicity. The samples NT10 and NT10-Sr have multiple nanocues, comprising bundles of nanotubes of less than or equal to 30 nm with bundle diameters between 100 and 400 nm separated by about 80 nm. Sr incorporation enhances proliferation of rat mesenchymal stem cells (MSCs) on the NT structure, especially NT10-Sr which promotes the spread of the MSCs into a polygonal osteoblastic shape. Both the NT and NT-Sr samples promote osteogenesis to varying degrees as indicated by gene expression and among the various samples, samples NT10-Sr3 and NT40-Sr significantly up-regulate the expressions of the osteogenesis related genes in the absence of an extra osteogenic agent. Samples NT10 and NT10-Sr generate big nodular alkaline phosphatase (ALP) products and induce extracellular matrix (ECM) mineralization, and the effects on NT10-Sr3 are most obvious due to the multiple scaled nanostructure and proper amount of incorporated Sr. In comparison, less ALP products and failure to induce ECM mineralization are observed from sample NT40-Sr, possibly due to cell function impairment by the uneven protein distribution. NT10-Sr3 which shows excellent osteogenic properties is very attractive and has large clinical potential.

Vascular lumen simulation and highly-sensitive nitric oxide detection using three-dimensional gelatin chip coupled to TiC/C nanowire arrays microelectrode.

Reproducing the physiological environment of blood vessels for the in vitro investigation of endothelial cell functions is very challenging. Here, we describe a vascular-like structure based on a three-dimensional (3D) gelatin chip with good compatibility and permeability which is also cost-effective and easy to produce. The controllable lumen diameter and wall thickness enable close mimicking of blood vessels in vitro. The 3D gelatin matrix between adjacent lumens is capable of generating soluble-factor gradients inside, and diffusion of molecules with different molecular weights through the matrix is studied. The cultured human umbilical vein endothelial cells proliferate on the gelatin lumen linings to form a vascular lumen. The hemodynamic behavior including adhesion, alignment of endothelial cells (ECs) under shear stress and pulsatile stretch is studied. Furthermore, a microelectrode comprising TiC/C nanowire arrays is fabricated to detect nitric oxide with sub-nM detection limits and NO generation from the cultured ECs is monitored in real time. This vascular model reproduces the surrounding parenchyma of endothelial cells and mimics the hemodynamics inside blood vessels very well, thereby enabling potential direct investigation of hemodynamics, angiogenesis, and tumor metastasis in vitro.

Direct growth of hexagonal Cd(OH)2 nanoplates from and on cadmium substrate.

Uniform hexagonal Cd(OH)2 nanoplates have been produced directly on Cd substrates by a hydrothermal process in alkaline solution containing (NH4)2S2)8 without the use of templates or surfactants. The Cd foil serves as both the Cd source and substrate. The morphology, structure, and composition of the Cd(OH)2 nanoplates are characterized by X-ray diffraction, electron microscopy, selected area electron diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The Cd(OH)2 nanoplates are single-crystalline and possess a well defined hexagonal shape. The thicknesses of hexagonal Cd(OH)2 nanoplates range from 30 to 80 nm and the lateral lengths are about 80-200 nm. The growth mechanism is also discussed.