Based on Fe and Ni prepared organic colloidal materials as efficient oxide nanozymes for chemiluminescence detection of GSH and Hg(II) ions.

Metal-organic gels (MOGs) are a type of metal-organic colloid material with a large specific surface area, loose porous structure, and open metal active sites. In this work, FeNi-MOGs were synthesized by the simple one-step static method, using Fe(III) and Ni(II) as the central metal ions and terephthalic acid as the organic ligand. The prepared FeNi-MOGs could effectively catalyze the chemiluminescence of luminol without the involvement of H2O2, which exhibited good catalytic activity. Then, the multifunctional detected platform was constructed for the detection of GSH and Hg2+, based on the antioxidant capacity of GSH, and the strong affinity between mercury ion (Hg2+) and GSH which inactivated the antioxidant capacity of GSH. The experimental limits of detection (LOD) for GSH and Hg2+ were 76 nM and 210 nM, and the detection ranges were 2-100 µM and 8-4000 µM, respectively. The as-proposed sensor had good performance in both detection limit and detection range of GSH and Hg2+, which fully met the needs of daily life. Surprisingly, the sensor had low detection limits and an extremely wide detection range for Hg2+, spanning five orders of magnitude. Furthermore, the detection of mercury ions in actual lake water and GSH in human serum showed good results, with recovery rates ranging from 90.10 % to 105.37 %, which proved that the method was accurate and reliable. The as-proposed sensor had great potential as the platform for GSH and Hg2+ detection applications.

Cobalt-containing borate bioactive glass fibers for treatment of diabetic wound.

Impaired angiogenesis is one of the predominant reasons for non-healing diabetic wounds. Cobalt is well known for its capacity to induce angiogenesis by stabilizing hypoxia-inducible factor-1α (HIF-1α) and subsequently inducing the production of vascular endothelial growth factor (VEGF). In this study, Co-containing borate bioactive glasses and their derived fibers were fabricated by partially replacing CaO in 1393B3 borate glass with CoO. Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) analyses were performed to characterize the effect of Co incorporation on the glass structure, and the results showed that the substitution promoted the transformation of [BO3] into [BO4] units, which endow the glass with higher chemical durability and lower reaction rate with the simulated body fluid (SBF), thereby achieving sustained and controlled Co2+ ion release. In vitro biological assays were performed to assess the angiogenic potential of the Co-containing borate glass fibers. It was found that the released Co2+ ion significantly enhanced the proliferation, migration and tube formation of the Human Umbilical Vein Endothelial Cells (HUVECs) by upregulating the expression of angiogenesis-related proteins such as HIF-1α and VEGF. Finally. In vivo results demonstrated that the Co-containing fibers accelerated full-thickness skin wound healing in streptozotocin (STZ)-induced diabetic rat model by promoting angiogenesis and re-epithelialization.

Evaluation of 'surgery-friendly' bone scaffold characteristics: 3D printed ductile BG/PCL scaffold with high inorganic content to repair critical bone defects.

The repair of irregular and complex critical bone defects remains a challenge in clinical practice. The application of 3D-printed bioceramics particle/polymer composite scaffolds in bone tissue engineering has been widely studied. At present, the inorganic particle content of the composite scaffolds is generally low, resulting in poor osteogenic activity. However, scaffold with high inorganic content are highly brittle, difficult to operate during surgery, and cannot be in close contact with surrounding bones. Therefore, it is of great significance to design a 'surgery-friendly' scaffold with high bioceramic content and good ductility. In this study, we used the solvent method to add high concentration (wt% 70%) bioglass (BG) into polycaprolactone (PCL), and polyethylene glycol was used as plasticizer to prepare 70% BG/PCL composite scaffolds with high ductility using 3D printing technology.In vitroexperiments showed that the scaffold had good mechanical properties: easy extension, easy folding and strong compressive resistance. It also showed good performance in biocompatibility and osteogenic activity. It was further observed that compared with pure BG or PCL implantation, the scaffold with higher BG content could have more new bone tissue appeared after 12 weeks. All these results indicate that 3D-printed 70% BG/PCL scaffolds have great potential for personalized repair of bone defects.

Pore Size of 3D-Printed Polycaprolactone/Polyethylene Glycol/Hydroxyapatite Scaffolds Affects Bone Regeneration by Modulating Macrophage Polarization and the Foreign Body Response.

3D-printed porous bioactive ceramic scaffolds have been widely used in bone defect repair. However, material implantation is often accompanied by a foreign body response (FBR), which may affect host tissue regeneration. The physical properties of biomaterials, including shape, pore size, and porosity, control the relevant immune responses during tissue regeneration. To the best of our knowledge, the effect of the pore size of 3D-printed scaffolds on the immune response and bone-biomaterial integration has not been studied in vivo. Polycaprolactone/polyethylene glycol/hydroxyapatite (PCL/PEG/HA) bioactive scaffolds with different pore sizes, including 209.9 ± 77.1 µm (P200), 385.5 ± 28.6 µm (P400), and 582.1 ± 27.2 µm (P600), were prepared with a pneumatic extrusion 3D printer. Compared with other pore sizes, P600 significantly reduced the FBR and induced more M2 macrophage infiltration, vascular ingrowth, and new bone formation. Immunohistochemical staining revealed that the MyD88 protein might be involved in macrophage polarization-related signal transduction in response to the pore size. Based on these results, bone regeneration requires the active participation of the immune response, and the P600 PCL/PEG/HA scaffold is a preferable candidate for the repair of bone defects.

Utilizing dual carriers assisted by enzyme digestion chemiluminescence signal enhancement strategy simultaneously detect tumor markers CEA and AFP.

To measure two tumor biomarkers, alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA), a dual-carrier CL sensor with restriction enzyme digestion (Exo I) and aptamer technology utilizing gold nanoparticles (hydroxylamine amplification) and horseradish peroxidase (HRP) as the CL signal enhancement in the sensing strategy was formed. These nanoparticles and nano-enzyme were precisely detected and tagged to the appropriate position attributable to the particular recognition of biotin and streptavidin. In this sensing strategy, target markers were further enriched and recognized sensitively by CL following enrichment, and matching strong chemical signals were collected under luminol catalysis, allowing for marker identification. For CEA (0.1-80 ng/mL) and AFP (2-500 ng/mL), the proposed method has a large linear range, with detection limits of 36.6 pg/mL and 0.94 ng/mL, respectively.

One-pot label-free dual-aptasensor as a chemiluminescent tool kit simultaneously detect adenosine triphosphate and chloramphenicol in foods.

The chemiluminescence (CL) analysis based on label-free dual-aptasensor was developed for simultaneous detection of adenosine triphosphate (ATP) and chloramphenicol (CAP) in food. Magnetic microspheres and polystyrene microspheres used as separating and immobilizing carriers which immobilized the two different captured DNA, respectively. Then these carriers were put in the mixture of ATPs, CAPs, ATP-binding aptamers and CAP-binding aptamers to make one-pot label-free recognized interaction. The more ATP or CAP molecules binding their aptamers, the less aptamers left on the surface of carriers reducing the CL signals. The proposed aptasensor exhibited high selectivity and sensitivity for ATP and CAP with the limits of detection of 3.76 × 10-8 moL/L and 2.48 × 10-8 moL/L, respectively. Finally, this method is further validated by measuring the recovery of ATP/CAP spiked in three different food samples.

Preparation and characterization of borosilicate-bioglass-incorporated sodium alginate composite wound dressing for accelerated full-thickness skin wound healing.

Full-thickness skin injury is a serious and intractable clinical problem. Wound dressing is urgently needed to treat serious skin defects or induce skin reconstruction. For the first time, we demonstrated a borosilicate bioglass (BBG)-incorporated sodium alginate (SA) wound dressing by a simple and effective technique for accelerated wound healing. The physical and chemical properties, in vitro and in vivo properties of SA-BBG composite wound dressing have been investigated. The results show that the SA-BBG composite dressing possesses good water absorption performance. The boron and silicon ions in BBG can maintain stable and sustained release. Most importantly, the SA-BBG composite wound dressing shows outstanding wound healing ability in full-thickness skin defects in rats. The wounds treated with SA-BBG composite dressing groups had almost closed at day 15. When the ratio of sodium alginate to bioglass in the sponge is 3:1, the wound healing effect is the best. In conclusion, the SA-BBG composite dressing shows great potential for application in skin wound healing and SA3BBG works best.

"The return of ceramic implants": Rose stem inspired dual layered modification of ceramic scaffolds with improved mechanical and anti-infective properties.

Nowadays, traditional ceramics for bone implants have considerably replaced by metal based biomedical materials, attributing to the friability of ceramics. However, ceramic implants possess excellent biocompatibility and longtime abrasion resistance. They should be more desirable for long-term uses of implants in case their fragility had been overcome. In the present work, inspired from natural rose, a dual-layer-modified ceramic scaffold was constructed by coating a superplastic layer of isocyanate (ISO) resin and a nano Zinc Oxide (nano-ZnO) layer on the ceramic scaffold. The ISO resin modification layer with 1 mm thickness, improved the mechanical properties of ceramic implants 2-3 times, and protect the ceramic implants from broken even drop from 1 m high. Moreover, such dual layered modification exhibited broad spectrum antibacterial behavior. In vivo biocompatible studies demonstrated that there was no obvious noticeable tissue damage in all major organs of mice after the implant surgeries.

ImmunoPET and Near-Infrared Fluorescence Imaging of Pancreatic Cancer with a Dual-Labeled Bispecific Antibody Fragment.

Dual-targeted imaging agents have shown improved targeting efficiencies in comparison to single-targeted entities. The purpose of this study was to quantitatively assess the tumor accumulation of a dual-labeled heterobifunctional imaging agent, targeting two overexpressed biomarkers in pancreatic cancer, using positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging modalities. A bispecific immunoconjugate (heterodimer) of CD105 and tissue factor (TF) Fab' antibody fragments was developed using click chemistry. The heterodimer was dual-labeled with a radionuclide (64Cu) and fluorescent dye. PET/NIRF imaging and biodistribution studies were performed in four-to-five week old nude athymic mice bearing BxPC-3 (CD105/TF+/+) or PANC-1 (CD105/TF-/-) tumor xenografts. A blocking study was conducted to investigate the specificity of the tracer. Ex vivo tissue staining was performed to compare TF/CD105 expression in tissues with PET tracer uptake to validate in vivo results. PET imaging of 64Cu-NOTA-heterodimer-ZW800 in BxPC-3 tumor xenografts revealed enhanced tumor uptake (21.0 ± 3.4%ID/g; n = 4) compared to the homodimer of TRC-105 (9.6 ± 2.0%ID/g; n = 4; p < 0.01) and ALT-836 (7.6 ± 3.7%ID/g; n = 4; p < 0.01) at 24 h postinjection. Blocking studies revealed that tracer uptake in BxPC-3 tumors could be decreased by 4-fold with TF blocking and 2-fold with CD105 blocking. In the negative model (PANC-1), heterodimer uptake was significantly lower than that found in the BxPC-3 model (3.5 ± 1.1%ID/g; n = 4; p < 0.01). The specificity was confirmed by the successful blocking of CD105 or TF, which demonstrated that the dual targeting with 64Cu-NOTA-heterodimer-ZW800 provided an improvement in overall tumor accumulation. Also, fluorescence imaging validated the PET imaging, allowing for clear delineation of the xenograft tumors. Dual-labeled heterodimeric imaging agents, like 64Cu-NOTA-heterodimer-ZW800, may increase the overall tumor accumulation in comparison to single-targeted homodimers, leading to improved imaging of cancer and other related diseases.

Engineering Intrinsically Zirconium-89 Radiolabeled Self-Destructing Mesoporous Silica Nanostructures for In Vivo Biodistribution and Tumor Targeting Studies.

A systematic study of in vitro and in vivo behavior of biodegradable mesoporous silica nanoparticles (bMSNs), designed to carry multiple cargos (both small and macromolecular drugs) and subsequently self-destruct following release of their payloads, is presented. Complete degradation of bMSNs is seen within 21 d of incubation in simulated body fluid. The as-synthesized bMSNs are intrinsically radiolabeled with oxophilic zirconium-89 (89Zr, t1/2 = 78.4 h) radionuclide to track their in vivo pharmacokinetics via positron emission tomography imaging. Rapid and persistent CD105 specific tumor vasculature targeting is successfully demonstrated in murine model of metastatic breast cancer by using TRC105 (an anti-CD105 antibody)-conjugated bMSNs. This study serves to illustrate a simple, versatile, and readily tunable approach to potentially overcome the current challenges facing nanomedicine and further the goals of personalized nanotheranostics.

Engineering of radiolabeled iron oxide nanoparticles for dual-modality imaging.

Over the last decade, radiolabeled iron oxide nanoparticles have been developed as promising contrast agents for dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI) or single-photon emission computed tomography/magnetic resonance imaging (SPECT/MRI). The combination of PET (or SPECT) with MRI can offer synergistic advantages for noninvasive, sensitive, high-resolution, and quantitative imaging, which is suitable for early detection of various diseases such as cancer. Here, we summarize the recent advances on radiolabeled iron oxide nanoparticles for dual-modality imaging, through the use of a variety of PET (and SPECT) isotopes by using both chelator-based and chelator-free radiolabeling techniques. WIREs Nanomed Nanobiotechnol 2016, 8:619-630. doi: 10.1002/wnan.1386.

Preparation and characterization of temperature-responsive magnetic composite particles for multi-modal cancer therapy.

The temperature-responsive magnetic composite particles were synthesized by emulsion-free polymerization of N-isopropylacrylamide (NIPAAm) and acrylamide (Am) in the presence of oleic acid-modified Fe(3)O(4) nanoparticles. The magnetic properties and heat generation ability of the composite particles were characterized. Furthermore, temperature and alternating magnetic field (AMF) triggered drug release behaviors of vitamin B(12)-loaded composite particles were also examined. It was found that composite particles enabled drug release to be controlled through temperature changes in the neighborhood of lower critical solution temperature. Continuous application of AMF resulted in an accelerated release of the loaded drug. On the other hand, intermittent AMF application to the composite particles resulted in an "on-off", stepwise release pattern. Longer release duration and larger overall release could be achieved by intermittent application of AMF as compared to continuous magnetic field. Such composite particles may be used for magnetic drug targeting followed by simultaneous hyperthermia and drug release.