Doxorubicin-loaded PEG-CdTe QDs conjugated with anti-CXCR4 mAbs: a novel delivery system for extramedullary multiple myeloma treatment.

Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor. High-dose chemotherapy with autologous stem cell transplantation, as a good option on early lines of therapy, has retained the survival benefit of youny EMM patients, but is intolerant for the majority of old patients because of drug cytotoxicity. To essentially address the intolerance above, we designed a CXCR4-PEG-CdTe-DOX (where CXCR4: chemokine receptor 4; PEG-CdTe: polyethylene glycol-modified cadmium telluride; DOX:doxorubicin) nanoplatform. First, CXCR4 is highly expressed in extramedullary plasma cells. Second, PEG-CdTe a drug carrier that controls drug release, can reduce adverse reactions, prolong drug (e.g, DOX) circulation time in the body, and form a targeting carrier after connecting antibodies. In vitro experiments showed CXCR4-PEG-CdTe-DOX facilitated intracellular drug accumulation through active CXCR4 targeting and released DOX into the microenvironment in a pH-controlled manner, enhancing the therapeutic efficacy and apoptosis rate of myeloma cells (U266). Therefore, targeted chemotherapy mediated by CXCR4-PEG-CdTe-DOX is a promising option for EMM treatment.

Aminobenzofuran-fused rhodamine dyes with deep-red to near-infrared emission for biological applications.

Aminobenzofuran-fused rhodamine dyes (AFR dyes) containing an amino group were constructed by an efficient condensation based on 3-coumaranone derivatives. AFR dyes exhibited significantly improved properties, including deep-red and near-infrared emissions, a large Stokes shift, good photostability, and wide pH stability. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium assay experiments show that these AFR dyes are biocompatible for their low cytotoxicity to both A549 and HeLa cells. Cell imaging data reveal that AFR1, AFR1E, and AFR2 are mainly located in the mitochondria, while AFR3 is a lysosome tracker. As far as we know, NIR AFR3 is the longest fluorescent rhodamine derivative containing the amino group. These amino group-containing AFR dyes hold great potential in fluorogenic detection, biomolecule labeling, and cell imaging.

Activates B lymphocytes and enhanced immune response: A promising adjuvant based on PLGA nanoparticle to improve the sensitivity of ZEN monoclonal antibody.

In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.

A dual-modal ROS generator based on multifunctional PDA-MnO2@Ce6 nanozymes for synergistic chemo-photodynamic antibacterial therapy.

The rapid emergence of drug-resistant bacteria has attracted great attention to exploring advanced antibacterial methods. However, single-modal antibacterial therapy cannot easily eliminate drug-resistant bacteria completely due to its low efficacy. Therefore, it is essential to achieve multi-modal antibacterial therapy effectively. Herein, a dual-modal ROS generator was designed based on photosensitive PDA-MnO2@Ce6/liposome (PMCL) nanozymes for synergistic chemo-photodynamic therapy. PMCL nanozymes adhere to bacteria through liposome-membrane fusion. Meanwhile, PMCL catalyzes endogenous hydrogen peroxide (H2O2) to generate hydroxyl radicals (˙OH) and singlet oxygen (1O2) under laser irradiation. Furthermore, the photothermal effect can accelerate the generation of ROS. Based on dual-enzyme activities (mimicking peroxidase and catalase) and photodynamic properties, PMCL achieves powerful antibacterial efficacy and mature bacterial biofilm eradication. With the synergistic chemo-photodynamic effects, bacterial populations decrease by >99.76% against Gram-positive S. aureus and Gram-negative E. coli. Notably, the synergistic antibacterial properties of PMCL nanozymes are further explored using a mouse wound model of S. aureus infection. This work fabricated an efficient dual-modal ROS generator to kill bacteria, further providing a new strategy for treating wound infection.

Matrix Metalloproteinase 9 is Regulated by LOX-1 and erk1/2 Pathway in Dental Peri-Implantitis.

BACKGROUND AND OBJECTIVE: Dental peri-implantitis, which can be caused by several different microbial factors, is characterized by inflammatory lesions of the surrounding hard and soft tissues of an oral implant. Matrix Metalloproteinase 9 (MMP9) is thought to be involved in the pathogenesis of peri-implantitis. However, the regulatory mechanism of MMP9 in peri-implantitis has not been fully elucidated. In this study, we tried to evaluate the regulatory mechanism of MMP9 in peri-implantitis. METHODS: We collected Peri-Implant Crevicular Fluid (PICF) from ten healthy implants and ten periimplantitis patients and compared their expression level of MMP9. We also cultured macrophages from the peripheral blood of healthy volunteers infected by Porphyromonas gingivalis to reveal the regulatory mechanism of MMP9 in peri-implantitis. Western blot, immunofluorescence staining and quantitative Polymerase Chain Reaction (RT-PCR) were used to better characterize the mechanism of MMP9. RESULTS: The expression of MMP9 was up-regulated in peri-implantitis patient PICF and P. gingivalis infected human macrophages. LOX-1, not dectin-1, was found to mediate MMP9 expression in human macrophages with P. gingivalis infection. Expression of Erk1/2 was responsible for infection-induced MMP9 expression. Finally, use of a broad-spectrum metalloproteinase inhibitor impaired LOX-1 expression in infected macrophages. CONCLUSION: Our results demonstrate that MMP9 is involved in dental peri-implantitis and is regulated by LOX-1 and Erk1/2. This LOX-1/MMP9 signaling pathway may represent a potential drug target for peri-implantitis.

A 3D porous NCNT sponge anode modified with chitosan and Polyaniline for high-performance microbial fuel cell.

A microbial fuel cell (MFC) is a potential bio-electrochemical technology that utilizes microorganisms to convert chemical energy into electrical energy. The low power output of MFCs remain the bottleneck for their practical applications. In this paper, a novel, biocompatible and bioelectrocatalytic composite chitosan-nitrogen doped carbon nanotubes-polyaniline (CS-NCNT-PANI) was prepared in situ on the 3D porous NCNT/sponge and applied to an MFC anode. The PANI was grafted on the CS-NCNT backbone to synthesize the ternary composite. This bioanode not only increased the active surface area and capacity but also facilitated bacterial adhesion and enrichment of microbes. Compared with the NCNT/sponge electrode, the charge transfer impedance of the ternary composite bioanode decreased from 14.07â€¯Ω to 2.25 Ω, and the maximum power density increased from 1.4 W·m-3 to 4.2 W·m-3; meanwhile, during the chronoamperometric experiment with a charge-discharge time of 60-60 min, the cumulative charge of the composite bioanode was 18,865.8 C·m-2, which is much higher than that of the NCNT/S anode (3625.3 C·m-2). High-throughput sequencing technology revealed that the ternary composite bioanode had good biocompatibility and high diversity. Therefore, this synthesized ternary composite is a promising candidate as a capacitive and biocompatible anode material in MFC.

Effects of different electrolytes for micro-arc oxidation on the bond strength between titanium and porcelain.

PURPOSE: The aim of this study is to investigate the effects of different electrolytes on the titanium-porcelain bond strength after micro-arc oxidation (MAO) treatment. METHODS: Three electrolytes at the same concentration were used as MAO reaction solutions: Na2SiO3, KF, and MgSiF6. Blasting treatment was chosen as a control. After MAO treatment in each electrolyte, the titanium-porcelain bond strengths were measured by the three-point bending test, as described in ISO 9693. The morphologies and elemental compositions of the MAO coating on the titanium substrate were evaluated by scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). The interface between the titanium and porcelain was also observed by SEM and EDS. RESULTS: The MAO coatings created in different electrolytes exhibited completely different morphologies and compositions. The bond strengths of the Na2SiO3 and MgSiF6 groups were significantly higher than those of the other groups (p<0.05). Additionally, the titanium-porcelain interfaces were compact in the former two groups, whereas pores and cracks were visible at the interfaces in the other groups. CONCLUSIONS: These results indicate that MAO treatment with an appropriate electrolyte could be an effective method to increase the titanium-porcelain bonding strength. According to ISO 9693, titanium-porcelain restorations subjected to MAO treatment with an appropriate electrolyte could be appropriate for clinical use.

Rational design of a binary metal alloy for chemical vapour deposition growth of uniform single-layer graphene.

Controlled growth of high-quality graphene is still the bottleneck of practical applications. The widely used chemical vapour deposition process generally suffers from an uncontrollable carbon precipitation effect that leads to inhomogeneous growth and strong correlation to the growth conditions. Here we report the rational design of a binary metal alloy that effectively suppresses the carbon precipitation process and activates a self-limited growth mechanism for homogeneous monolayer graphene. As demonstrated by an Ni-Mo alloy, the designed binary alloy contains an active catalyst component for carbon source decomposition and graphene growth and a black hole counterpart for trapping the dissolved carbons and forming stable metal carbides. This type of process engineering has been used to grow strictly single-layer graphene with 100% surface coverage and excellent tolerance to variations in growth conditions. With simplicity, scalability and a very large growth window, the presented approach may facilitate graphene research and industrial applications.