Upconverting Nanoparticles in Aqueous Media: Not a Dead-End Road. Avoiding Degradation by Using Hydrophobic Polymer Shells.

The stunning optical properties of upconverting nanoparticles (UCNPs) have inspired promising biomedical technologies. Nevertheless, their transfer to aqueous media is often accompanied by intense luminescence quenching, partial dissolution by water, and even complete degradation by molecules such as phosphates. Currently, these are major issues hampering the translation of UCNPs to the clinic. In this work, a strategy is developed to coat and protect ß-NaYF4 UCNPs against these effects, by growing a hydrophobic polymer shell (HPS) through miniemulsion polymerization of styrene (St), or St and methyl methacrylate mixtures. This allows one to obtain single core@shell UCNPs@HPS with a final diameter of ≈60-70 nm. Stability studies reveal that these HPSs serve as a very effective barrier, impeding polar molecules to affect UCNPs optical properties. Even more, it allows UCNPs to withstand aggressive conditions such as high dilutions (5 µg mL-1 ), high phosphate concentrations (100 mm), and high temperatures (70 °C). The physicochemical characterizations prove the potential of HPSs to overcome the current limitations of UCNPs. This strategy, which can be applied to other nanomaterials with similar limitations, paves the way toward more stable and reliable UCNPs with applications in life sciences.

SPION nanoparticles for delivery of dopaminergic isoquinoline and benzazepine derivatives.

Superparamagnetic iron nanoparticles (SPIONs) have become one of the most useful colloidal systems in nanomedicine. We report here the preparation of new hybrid core@shell systems based on SPION nanoparticles coated with a SiO2 shell (SPION@SiO2) and functionalized with carboxyl groups (SPION@SiO2-COOH). A series of new N-alkylamino- and N-alkylamido-terminated 1-phenyl- tetrahydroisoquinolines (THIQs) and 3-tetrahydrobenzazepines (THBs) derivatives presenting -SMe and -Cl groups, respectively, with potential dopaminergic activity, are synthesized and incorporated to the hybrid system. We include the synthetic details for THIQs and THBs derivatives preparation and investigate the influence of the terminal-functional group as well as the number of carbon atoms linked to THIQ and THB molecules during the coupling to the SPION@SiO2-COOH. Nuclear magnetic resonance (NMR) and electron ionization mass spectrometry (EI-MS) are used to characterize the synthesized THIQs and THBs. High-angle annular dark-field transmission electron microscopy (HAADF-TEM), energy dispersive X-ray transmission electron microscopy (EDX-TEM), and proton high-resolution magic angle spinning NMR spectroscopy1H HRMAS-NMR) are used to confirm the presence of THB and THIQ molecules onto the surface of the nanoparticles. The hybrid SPION@SiO2-THIQ and THB systems show significant activity toward the D2 receptor, reaching Ki values of about 20 nM, thus having potential application in the treatment of central nervous system (CNS) diseases.

Biocompatibility and Durability of Diazonium Adhesives on Dental Alloys.

PURPOSE: A new type of diazonium-based adhesive has been recently developed by our team to bind dental alloys (Titanium, stainless steel, and cobalt chromium) to dental polymers. Here, we explored the endurance of the resulting adhesive after thermal-cycling and autoclave aging. MATERIALS AND METHODS: Polished samples of titanium (Ti), stainless steel (SS) and cobalt chromium (Co-Cr) were coated with a diazonium-based adhesive. Untreated samples served as controls (n = 12 per each condition). X-ray photoelectron spectroscopy (XPS) was performed to characterize the elemental compositions of the different surfaces. Biocompatibility of the coated alloys was assessed with human gingival fibroblasts (HGF). Inductively coupled plasma (ICP) and total organic carbon (TOC) analyses were used to quantify the ions and organic matters released from the diazonium coated alloys. Endurance of the adhesives was assessed by exposing the samples to autoclaving and thermal-cycling. The tensile strength of the poly(methylmethacrylate) (PMMA)-alloy bond was also tested. RESULTS: Results of mechanical testing demonstrated a higher endurance of the coated CoCr, Ti, and SS compared to the uncoated alloys. The human fibroblasts cultured on the substrates remained alive and metabolically active, and the coatings did not release significant amounts of toxic chemicals in solutions. CONCLUSIONS: The results further support the use of diazonium-based adhesives as new coupling agents for dental applications.

Photochemical Ligation to Ultrasensitive DNA Detection with Upconverting Nanoparticles.

In this work, we explore a photochemical ligation reaction to covalently modify oligonucleotide-conjugated upconverting nanoparticles (UCNPs) in the presence of a specific target DNA sequence. The target sequence acts as a hybridization template, bringing together a biotinylated photoactivatable oligonucleotide probe and the oligonucleotide probe that is attached to UCNPs. The illumination of the UCNPs by NIR light to generate UV emission internally or illuminating the photoactivatable probe directly by an external UV light promotes the photochemical ligation reaction, yielding covalently biotin functionalized UCNPs that can be selectively captured in streptavidin-coated microwells. Following this strategy, we developed a DNA sensor with a limit of detection of 1 × 10-18 mol per well (20 fM). In addition, we demonstrate the possibility to create UCNP patterns on the surface of solid supports upon NIR illumination that are selectively formed under the presence of the target oligonucleotide.

Functionalized ZnO nanowires for microcantilever biosensors with enhanced binding capability.

An efficient way to increase the binding capability of microcantilever biosensors is here demonstrated by growing zinc oxide nanowires (ZnO NWs) on their active surface. A comprehensive evaluation of the chemical compatibility of ZnO NWs brought to the definition of an innovative functionalization method able to guarantee the proper immobilization of biomolecules on the nanostructured surface. A noteworthy higher amount of grafted molecules was evidenced with colorimetric assays on ZnO NWs-coated devices, in comparison with functionalized and activated silicon flat samples. ZnO NWs grown on silicon microcantilever arrays and activated with the proposed immobilization strategy enhanced the sensor binding capability (and thus the dynamic range) of nearly 1 order of magnitude, with respect to the commonly employed flat functionalized silicon devices. Graphical Abstract An efficient way to increase the binding capability of microcantilever biosensors is represented by growing zinc oxide nanowires (ZnO NWs) on their active surface. ZnO NWs grown on silicon microcantilever arrays and activated with an innovative immobilization strategy enhanced the sensor binding capability of nearly 1 order of magnitude, with respect to the commonly employed flat functionalized silicon devices.

Decontamination of titanium implants using physical methods.

OBJECTIVES: Current decontamination methods of titanium (Ti) implant present limited success in achieving predictable re-osseointegration. We hypothesized that even though these techniques could be useful in elimination of bacteria, they might be unsuccessful in removing organic contaminants and restoring the original surface composition. The aim of this study was to assess the effect of four decontamination methods on the surface chemistry and bacterial load of biofilm-contaminated implant surfaces in order to improve implant surface decontamination. MATERIAL AND METHODS: The ability of clinically available methods such as metal and plastic curettes, Ti brushes and Er: YAG laser to decontaminate Ti implant surfaces was assessed. Surface morphology, chemical composition and properties of machined Ti discs (Ø 5.0 and 1.0 mm thick) were analysed before and after oral biofilm contamination using scanning electron microscope and X-ray photoelectron spectroscopy. The presence and viability of bacteria were evaluated with live-dead assays. RESULTS: Biofilm contamination created an organic layer rich in hydrocarbons and bacteria that covered entirely the Ti surfaces. This organic layer has tightly adhered to Ti surfaces and could not be completely removed with any of the methods assessed. Ti brushes achieved greater elimination of organic contaminants and bacteria than curettes and Er: YAG laser; however, none of them was able to restore the original surface chemistry. Alternatively, Er: YAG laser-treated surfaces showed the lowest live-to-dead bacterial ratio. CONCLUSIONS: Ti brushes were more effective than curettes (metal or plastic) and Er: YAG laser in decontaminating Ti implant surfaces, although none of these techniques was able to completely eliminate surface contamination. Er: YAG laser was more effective than curettes and Ti brushes in killing the biofilm bacteria.

Two-Dimensional Magnesium Phosphate Nanosheets Form Highly Thixotropic Gels That Up-Regulate Bone Formation.

Hydrogels composed of two-dimensional (2D) nanomaterials have become an important alternative to replace traditional inorganic scaffolds for tissue engineering. Here, we describe a novel nanocrystalline material with 2D morphology that was synthesized by tuning the crystallization of the sodium-magnesium-phosphate system. We discovered that the sodium ion can regulate the precipitation of magnesium phosphate by interacting with the crystal's surface causing a preferential crystal growth that results in 2D morphology. The 2D nanomaterial gave rise to a physical hydrogel that presented extreme thixotropy, injectability, biocompatibility, bioresorption, and long-term stability. The nanocrystalline material was characterized in vitro and in vivo and we discovered that it presented unique biological properties. Magnesium phosphate nanosheets accelerated bone healing and osseointegration by enhancing collagen formation, osteoblasts differentiation, and osteoclasts proliferation through up-regulation of COL1A1, RunX2, ALP, OCN, and OPN. In summary, the 2D magnesium phosphate nanosheets could bring a paradigm shift in the field of minimally invasive orthopedic and craniofacial interventions because it is the only material available that can be injected through high gauge needles into bone defects in order to accelerate bone healing and osseointegration.

Systemic administration of omeprazole interferes with bone healing and implant osseointegration: an in vivo study on rat tibiae.

BACKGROUND: Proton pump inhibitors, over-the-counter drugs taken by millions of patients, diminish bone accrual. Accordingly, we hypothesized that these drugs could impair bone healing and implant osseointegration. This study investigated the effect of post-operative systemic administration of omeprazole on bone healing and implant osseointegration in rat tibiae. METHODS: In 24 Sprague-Dawley rats, a titanium implant was placed in the left tibia, and a bone defect was created in the right tibia. During the 2 weeks following surgery, 12 rats were treated with omeprazole (5 mg/kg, daily) and the other 12 with saline. Then, after euthanasia, the volume (mm(3) ) of the cortical defect and the percentages of newly formed bone in the defect, were assessed using microcomputed tomography; peri-implant bone volume/tissue volume and bone-implant contact percentage were assessed by histomorphometry. RESULTS: Omeprazole-treated rats presented larger cortical defects (2.75 ± 0.59 mm(3) , p = 0.003 versus 2.11 ± 0.36 mm(3) ; p = 0.002) and a lower percentage of newly formed bone in the defects (28.62 ± 13.12; 45.89 ± 9.73; p = 0.003) than controls. Omeprazole-treated rats presented lower peri-implant bone volume/tissue volume (14.3 ± 7.3% versus 30.8 ± 11.0%; p < 0.001) and bone-implant contact (23.3 ± 10.8% versus 41.8 ± 13.3%; p < 0.001) than controls. CONCLUSION: Systemically administered omeprazole impairs bone healing and implant osseointegration.

Propranolol enhances bone healing and implant osseointegration in rats tibiae.

BACKGROUND: Propranolol, a non-selective ß-blocker widely used to treat cardiovascular conditions, favours bone accrual. Accordingly, we hypothesized that propranolol could be useful for improving bone healing and osseointegration. This in vivo study was designed to investigate the effect of propranolol on bone healing and osseointegration in rats' tibiae. METHODS: On 24 Sprague-Dawley rats, a unicortical defect was created in the right tibial metaphysis of each rat and a custom-made titanium implant was placed in the left tibia. Animals were then assigned into two groups (n = 12, each group) and treated daily with either propranolol (5 mg/kg: subcutaneous) or saline, for 2 weeks. Then, after killing, the volume of the cortical defects (mm3) and the percentages of newly formed bone in the defects, were assessed with microcomputed tomography; bone-implant contact percentage and peri-implant bone volume/tissue volume were assessed by histomorphometry. RESULT: Propranolol-treated rats presented smaller cortical defects (1.56 ± 0.28 mm3 versus 2.04 ± 0.29 mm3 , p < 0.001) with more bone volume/tissue volume (60.6 ± 7.9% versus 41.1 ± 10.2%, p < 0.001) compared to saline-treated rats. Propranolol also enhanced osseointegration as propranolol-treated rats presented higher bone-implant-contact (65.0 ± 13.1% versus 42.5 ± 8.8%, p < 0.001) and peri-implant bone volume/Tissue volume (73.8 ± 10.1% versus 56.9 ± 5.7%, p = 0.007) than saline-treated rats. CONCLUSION: Propranolol enhanced bone healing and implant osseointegration.

Temperature controlled fluorescence on Au@Ag@PNIPAM-PTEBS microgels: effect of the metal core size on the MEF extension.

In this work, we present a novel method to produce thermoresponsive, monodisperse microgels which display temperature-dependent photoluminescence. The system is based on bimetallic cores of Au@Ag encapsulated within thermoresponsive poly(N-isopropylacrylamide) microgels and coated with a photoluminescent polymer (poly[2-(3-thienyl)ethoxy-4-butylsulfonate] (PTEBS) using the Layer-by-Layer technique. The electromagnetic radiation used to excite the PTEBS induces a local electromagnetic field on the surface of the bimetallic cores that enhances the excitation and emission rates of the PTEBS, yielding a metal enhanced fluorescence (MEF). This effect was studied as a function of the bimetallic core size and the separation distance between the PTEBS and the bimetallic cores. Our results permit evaluation of the effect that the metallic core size of colloidal particles exerts on the MEF for the first time, and prove the relevance of the metallic cores to extend the effect far away from the metallic surface.

Impact of excitation pulse width on the upconversion luminescence lifetime of NaYF4:Yb3+,Er3+ nanoparticles.

The upconversion luminescence (UCL) lifetime has a wide range of applications, serving as a critical parameter for optimizing the performance of upconversion nanoparticles (UCNPs) in various fields. It is crucial to understand that this lifetime does not directly correlate with the decay time of the emission level; rather, it represents a compilation of all the physical phenomena taking place in the upconversion process. To delve deeper into this, we analyzed the dependence of the UCL lifetime on the excitation pulse width for ß-NaYF4:Yb3+,Er3+ nanoparticles. The results revealed a significant increase in the UCL lifetime with both the excitation pulse width and the excitation intensity. The laser fluence was identified as the parameter governing the UCL decay dynamics. We showcased the universality of the pulse-width-dependent UCL lifetime phenomenon by employing UCNPs of various sizes, surface coatings, host matrices, Yb3+ and Er3+ ratios, and dispersing UCNPs in different solvents. Theoretical explanations for the experimental findings were derived through a rate equation analysis. Finally, we discussed the implications of these results in UCNP-FRET (Förster resonance energy transfer)-based applications.

Reduced Graphene Oxide Embedded with ZnS Nanoparticles as Catalytic Cathodic Material for Li-S Batteries.

Lithium-sulfur technology is a strong candidate for the future generation of batteries due to its high specific capacity (1675 mAh g-1), low cost, and environmental impact. In this work, we propose a facile and solvent-free microwave synthesis for a composite material based on doped (sulfur and nitrogen) reduced graphene oxide embedded with zinc sulfide nanoparticles (SN-rGO/ZnS) to improve the battery performance. The chemical-physical characterization (XRD, XPS, FESEM, TGA) confirmed the effectiveness of the microwave approach in synthesizing the composite materials and their ability to be loaded with sulfur. The materials were then thoroughly characterized from an electrochemical point of view (cyclic voltammetry, galvanostatic cycling, Tafel plot, electrochemical impedance spectroscopy, and Li2S deposition test); the SN-rGO/ZnS/S8 cathode showed a strong affinity towards polysulfides, thus reducing their loss by diffusion and improving redox kinetics, allowing for faster LiPSs conversion. In terms of performance, the composite-based cathode increased the specific capacity at high rate (1 C) from 517 to 648 mAh g-1. At the same time, more stable behavior was observed at 0.5 C with capacity retention at the 750th cycle, where it was raised from 32.5% to 48.2%, thus confirming the beneficial effect of the heteroatomic doping process and the presence of zinc sulfide nanoparticles.

Morphology Effects on Electro- and Photo-Catalytic Properties of Zinc Oxide Nanostructures.

Environmental problems are among the most pressing issues in the modern world, including the shortage of clean drinking water partially caused by contamination from various industries and the excessive emission of CO2 primarily from the massive use of fossil fuels. Consequently, it is crucial to develop inexpensive, effective, and environmentally friendly methods for wastewater treatment and CO2 reduction, turning them into useful feedstocks. This study explores a unique method that addresses both challenges by utilizing ZnO, which is recognized as one of the most active semiconductors for photocatalysis, as well as a cost-effective electrocatalyst for the CO2 reduction reaction (CO2RR). Specifically, we investigate the influence of the morphology of various ZnO nanostructures synthesized via different low-cost routes on their photocatalytic properties for degrading the rhodamine-B dye (RhB) and on their electrocatalytic performance for the CO2RR. Our results show that the ZnO lamella morphology achieves the best performance compared to the nanorod and nanoparticle structures. This outcome is likely attributed to the lamella's higher aspect ratio, which plays a critical role in determining the structural, optical, and electrical properties of ZnO.

Insight into Sonoluminescence Augmented by ZnO-Functionalized Nanoparticles.

Recent advances in optical imaging techniques rely on the use of nanosized contrast agents for in vitro and in vivo applications. We report on an imaging method based on the inertial cavitation of ultrasound-irradiated water solutions that lead to sonoluminescence (SL), here, newly proposed in combination with semiconductor nanoparticles, in particular, aminopropyl-functionalized zinc oxide nanocrystals. The obtained measurements confirm the ability of such nanocrystals to increase the sonoluminescence emission, together with the ability to modify the SL spectrum when compared to the pure water behavior. In particular, it is shown that the UV component of SL is absorbed by the semiconductor behavior that is also confirmed in different biologically relevant media. Finally, optical images of nanocrystal-assisted SL are acquired for the first time, in particular, in biological buffers, revealing that at low ultrasound intensities, SL is measurable only when the nanocrystals are present in solution. All of these results witness the role of amine-functionalized zinc oxide nanocrystals for sonoluminescence emission, which makes them very good candidates as efficient nanocontrast agents for SL imaging for biological and biomedical applications.

Synthesis of thermosensitive microgels with a tunable magnetic core.

In this work, we describe a new methodology for the preparation of monodisperse and thermosensitive microgels with magnetic core. In order to produce such a material, hydrophobic magnetic Fe(3)O(4) nanoparticles were prepared by two methods: thermal decomposition and coprecipitation. The surface of these nanoparticles was modified by addition of 3-butenoic acid, and after that these nanoparticles were dispersed in water and submitted to free radical polymerization at 70 °C in the presence of N-isopropylacrylamide (NIPAM) and bisacrylamide. The result of this reaction was monodisperse microgels with a magnetic core. By varying the amount of 3-butenoic acid, it was possible to obtain hybrid microgels with different magnetic core sizes and different architectures.

Editorial for Special Issue: ZnO Nanostructures for Tissue Regeneration, Drug-Delivery and Theranostics Applications.

In recent years, zinc oxide (ZnO)-based nanomaterials have attracted a great deal of interest thanks to their outstanding and multifunctional properties [...].

ZnO Materials as Effective Anodes for the Photoelectrochemical Regeneration of Enzymatically Active NAD.

This work reports the study of ZnO-based anodes for the photoelectrochemical regeneration of the oxidized form of nicotinamide adenine dinucleotide (NAD+). The latter is the most important coenzyme for dehydrogenases. However, the high costs of NAD+ limit the use of such enzymes at the industrial level. The influence of the ZnO morphologies (flower-like, porous film, and nanowires), showing different surface area and crystallinity, was studied. The detection of diluted solutions (0.1 mM) of the reduced form of the coenzyme (NADH) was accomplished by the flower-like and the porous films, whereas concentrations greater than 20 mM were needed for the detection of NADH with nanowire-shaped ZnO-based electrodes. The photocatalytic activity of ZnO was reduced at increasing concentrations of NAD+ because part of the ultraviolet irradiation was absorbed by the coenzyme, reducing the photons available for the ZnO material. The higher electrochemical surface area of the flower-like film makes it suitable for the regeneration reaction. The illumination of the electrodes led to a significant increase on the NAD+ regeneration with respect to both the electrochemical oxidation in dark and the only photochemical reaction. The tests with formate dehydrogenase demonstrated that 94% of the regenerated NAD+ was enzymatically active.

Iron-Doped ZnO Nanoparticles as Multifunctional Nanoplatforms for Theranostics.

Zinc oxide nanoparticles (ZnO NPs) are currently among the most promising nanomaterials for theranostics. However, they suffer from some drawbacks that could prevent their application in nanomedicine as theranostic agents. The doping of ZnO NPs can be effectively exploited to enhance the already-existing ZnO properties and introduce completely new functionalities in the doped material. Herein, we propose a novel synthetic approach for iron-doped ZnO (Fe:ZnO) NPs as a multifunctional theranostic nanoplatform aimed at cancer cell treatment. Pure ZnO and Fe:ZnO NPs, with two different levels of iron doping, were synthesized by a rapid wet-chemical method and analyzed in terms of morphology, crystal structure and chemical composition. Interestingly, Fe:ZnO NPs featured bioimaging potentialities thanks to superior optical properties and novel magnetic responsiveness. Moreover, iron doping provides a way to enhance the electromechanical behavior of the NPs, which are then expected to show enhanced therapeutic functionalities. Finally, the intrinsic therapeutic potentialities of the NPs were tested in terms of cytotoxicity and cellular uptake with both healthy B lymphocytes and cancerous Burkitt's lymphoma cells. Furthermore, their biocompatibility was tested with a pancreatic ductal adenocarcinoma cell line (BxPC-3), where the novel properties of the proposed iron-doped ZnO NPs can be potentially exploited for theranostics.

Oligonucleotide sensor based on magnetic capture and photoligation of upconverting nanoparticles in solid surfaces.

In this work, we present a luminescence platform that can be used as point of care system for determining the presence and concentration of specific oligonucleotide sequences. This sensor exhibited a limit of detection as low as 50 fM by means of: (i) the use of single-stranded DNA (ssDNA) functionalized magnetic microparticles that captured and concentrated ssDNA-upconverting nanoparticles (ssDNA-UCNPs) on a solid support, when the target sequence (miR-21-5p DNA-analogue) was in the sample, and (ii) a photoligation reaction that covalently linked the ssDNA-UCNPs and the ssDNA magnetic microparticles, allowing stringent washes. The presented sensor showed a similar limit of detection when the assays were conducted in samples containing total miRNA extracted from human serum, demonstrating its suitability for detecting small specific oligonucleotide sequences under real-like conditions. The strategy of combining UCNPs, magnetic microparticles, and a photoligation reaction provides new insight into low-cost, rapid, and ultra-sensitive detection of oligonucleotide sequences.

Biomimetic trace metals improve bone regenerative properties of calcium phosphate bioceramics.

The bone regenerative capacity of synthetic calcium phosphates (CaPs) can be enhanced through the enrichment with selected metal trace ions. However, defining the optimal elemental composition required for bone formation is challenging due to many possible concentrations and combinations of these elements. We hypothesized that the ideal elemental composition exists in the inorganic phase of the bone extracellular matrix (ECM). To study our hypothesis, we first obtained natural hydroxyapatite through the calcination of bovine bone, which was then investigated its reactivity with acidic phosphates to produce CaP cements. Bioceramic scaffolds fabricated using these cements were assessed for their composition, properties, and in vivo regenerative performance and compared with controls. We found that natural hydroxyapatite could react with phosphoric acid to produce CaP cements with biomimetic trace metals. These cements present significantly superior in vivo bone regenerative performance compared with cements prepared using synthetic apatite. In summary, this study opens new avenues for further advancements in the field of CaP bone biomaterials by introducing a simple approach to develop biomimetic CaPs. This work also sheds light on the role of the inorganic phase of bone and its composition in defining the regenerative properties of natural bone xenografts.