Boron Nitride Nanosheets Induce Lipid Accumulation and Autophagy in Human Alveolar Lung Epithelial Cells Cultivated at Air-Liquid Interface.

Hexagonal boron nitride (hBN) is an emerging 2D material attracting significant attention due to its superior electrical, chemical, and therapeutic properties. However, inhalation toxicity mechanisms of hBN in human lung cells are poorly understood. Here, cellular interaction and effects of hBN nanosheets is investigated in alveolar epithelial cells cultured on porous inserts and exposed under air-liquid interface conditions for 24 h. hBN is taken up by the cells as determined in a label-free manner via RAMAN-confocal microscopy, ICP-MS, TEM, and SEM-EDX. No significant (p > 0.05) effects are observed on cell membrane integrity (LDH release), epithelial barrier integrity (TEER), interleukin-8 cytokine production or reactive oxygen production at tested dose ranges (1, 5, and 10 µg cm-2). However, it is observed that an enhanced accumulation of lipid granules in cells indicating the effect of hBN on lipid metabolism. In addition, it is observed that a significant (p < 0.05) and dose-dependent (5 and 10 µg cm-2) induction of autophagy in cells after exposure to hBN, potentially associated with the downstream processing and breakdown of excess lipid granules to maintain lipid homeostasis. Indeed, lysosomal co-localization of lipid granules supporting this argument is observed. Overall, the results suggest that the continuous presence of excess intracellular lipids may provoke adverse outcomes in the lungs.

Protein Aggregation on Metal Oxides Governs Catalytic Activity and Cellular Uptake.

Engineering of catalytically active inorganic nanomaterials holds promising prospects for biomedicine. Catalytically active metal oxides show applications in enhancing wound healing but have also been employed to induce cell death in photodynamic or radiation therapy. Upon introduction into a biological system, nanomaterials are exposed to complex fluids, causing interaction and adsorption of ions and proteins. While protein corona formation on nanomaterials is acknowledged, its modulation of nanomaterial catalytic efficacy is less understood. In this study, proteomic analyses and nano-analytic methodologies quantify and characterize adsorbed proteins, correlating this protein layer with metal oxide catalytic activity in vitro and in vivo. The protein corona comprises up to 280 different proteins, constituting up to 38% by weight. Enhanced complement factors and other opsonins on nanocatalyst surfaces lead to their uptake into macrophages when applied topically, localizing >99% of the nanomaterials in tissue-resident macrophages. Initially, the formation of the protein corona significantly reduces the nanocatalysts' activity, but this activity can be partially recovered in endosomal conditions due to the proteolytic degradation of the corona. Overall, the research reveals the complex relationship between physisorbed proteins and the catalytic characteristics of specific metal oxide nanoparticles, providing design parameters for optimizing nanocatalysts in complex biological environments.

Correlative Cathodoluminescence Electron Microscopy: Immunolabeling Using Rare-Earth Element Doped Nanoparticles.

The understanding of living systems and their building blocks relies on the assessment of structure-function relationships at the nanoscale. Although electron microscopy (EM) gives access to ultrastructural imaging with nanometric resolution, the unambiguous localization of specific molecules is challenging. An EM approach capable of localizing biomolecules with respect to the cellular ultrastructure will offer a direct route to the molecular blueprints of biological systems. In an approach departing from conventional correlative imaging, an electron beam may be used as excitation source to generate optical emission with nanometric resolution, that is, cathodoluminescence (CL). Once suitable luminescent labels become available, CL may be harnessed to enable identification of biomolecule labels based on spectral signatures rather than electron density and size. This work presents CL-enabled immunolabeling based on rare-earth element doped nanoparticle-labels allowing specific molecules to be visualized at nanoscale resolution in the context of the cellular ultrastructure. Folic acid decorated nanoparticles exhibiting single particle CL emission are employed to specifically label receptors and identify characteristic receptor clustering on the surface of cancer cells. This demonstration of CL immunotargeting gives access to protein localization in the context of the cellular ultrastructure and paves the way for immunolabeling of multiple proteins in EM.

Transformation of Nanoscale and Ionic Cu and Zn during the Incineration of Digested Sewage Sludge (Biosolids).

Engineered nanoparticles (NP) discharged to sewers are efficiently retained by wastewater treatment plants and accumulate in the sewage sludge, which is commonly digested. The resulting biosolids are either used as fertilizer or incinerated. In this study, we address the transformation of Cu and Zn during sewage sludge incineration and evaluate whether the form of Cu or Zn (nanoparticulate versus dissolved) added to the digested sewage sludge affects the fate of the metals during incineration. We spiked CuO-NP, dissolved CuSO4, ZnO-NP, or dissolved ZnSO4 into anaerobically digested sewage sludge to reach Cu and Zn concentrations of ≈2500 and ≈3700 mg/kg and maintained the sludge under mesophilic, anaerobic conditions for 24 h. Subsequently, the sludge was incinerated in a pilot fluidized bed reactor. The speciation of Cu and Zn in the sludge, derived from X-ray absorption spectroscopy measurements, was dominated by sulfidic species, with >90% of Cu and >60% of Zn coordinated to reduced sulfur groups. In the ash, both Cu (>60%) and Zn (≈100%) were coordinated to oxygen. The chemical speciation of Cu and Zn in the ashes was independent of whether they were spiked in the dissolved or nanoparticulate form and closely matched the speciation of Cu and Zn observed in ashes from full-scale incinerators.

Quantification of Carbon Nanotubes in Environmental Matrices: Current Capabilities, Case Studies, and Future Prospects.

Carbon nanotubes (CNTs) have numerous exciting potential applications and some that have reached commercialization. As such, quantitative measurements of CNTs in key environmental matrices (water, soil, sediment, and biological tissues) are needed to address concerns about their potential environmental and human health risks and to inform application development. However, standard methods for CNT quantification are not yet available. We systematically and critically review each component of the current methods for CNT quantification including CNT extraction approaches, potential biases, limits of detection, and potential for standardization. This review reveals that many of the techniques with the lowest detection limits require uncommon equipment or expertise, and thus, they are not frequently accessible. Additionally, changes to the CNTs (e.g., agglomeration) after environmental release and matrix effects can cause biases for many of the techniques, and biasing factors vary among the techniques. Five case studies are provided to illustrate how to use this information to inform responses to real-world scenarios such as monitoring potential CNT discharge into a river or ecotoxicity testing by a testing laboratory. Overall, substantial progress has been made in improving CNT quantification during the past ten years, but additional work is needed for standardization, development of extraction techniques from complex matrices, and multimethod comparisons of standard samples to reveal the comparability of techniques.

Effect of nanoparticles on red clover and its symbiotic microorganisms.

BACKGROUND: Nanoparticles are produced and used worldwide and are released to the environment, e.g., into soil systems. Titanium dioxide (TiO2) nanoparticles (NPs), carbon nanotubes (CNTs) and cerium dioxide (CeO2) NPs are among the ten most produced NPs and it is therefore important to test, whether these NPs affect plants and symbiotic microorganisms that help plants to acquire nutrients. In this part of a joint companion study, we spiked an agricultural soil with TiO2 NPs, multi walled CNTs (MWCNTs), and CeO2 NPs and we examined effects of these NP on red clover, biological nitrogen fixation by rhizobia and on root colonization of arbuscular mycorrhizal fungi (AMF). We also tested whether effects depended on the concentrations of the applied NPs. RESULTS: Plant biomass and AMF root colonization were not negatively affected by NP exposure. The number of flowers was statistically lower in pots treated with 3 mg kg(-1) MWCNT, and nitrogen fixation slightly increased at 3000 mg kg(-1) MWCNT. CONCLUSIONS: This study revealed that red clover was more sensitive to MWCNTs than TiO2 and CeO2 NPs. Further studies are necessary for finding general patterns and investigating mechanisms behind the effects of NPs on plants and plant symbionts.

Vertical transport and plant uptake of nanoparticles in a soil mesocosm experiment.

BACKGROUND: Agricultural soils represent a potential sink for increasing amounts of different nanomaterials that nowadays inevitably enter the environment. Knowledge on the relation between their actual exposure concentrations and biological effects on crops and symbiotic organisms is therefore of high importance. In this part of a joint companion study, we describe the vertical translocation as well as plant uptake of three different titanium dioxide (nano-)particles (TiO2 NPs) and multi-walled carbon nanotubes (MWCNTs) within a pot experiment with homogenously spiked natural agricultural soil and two plant species (red clover and wheat). RESULTS: TiO2 NPs exhibited limited mobility from soil to leachates and did not induce significant titanium uptake into both plant species, although average concentrations were doubled from 4 to 8 mg/kg Ti at the highest exposures. While the mobility of MWCNTs in soil was limited as well, microwave-induced heating suggested MWCNT-plant uptake independent of the exposure concentration. CONCLUSIONS: Quantification of actual exposure concentrations with a series of analytical methods confirmed nominal ones in soil mesocosms with red clover and wheat and pointed to low mobility and limited plant uptake of titanium dioxide nanoparticles and carbon nanotubes.

Potential of hyperspectral imaging microscopy for semi-quantitative analysis of nanoparticle uptake by protozoa.

Hyperspectral imaging with enhanced darkfield microscopy (HSI-M) possesses unique advantages in its simplicity and non-invasiveness. In consideration of the urgent need for profound knowledge on the behavior and effects of engineered nanoparticles (NPs), here, we determined the capability of HSI-M for examining cellular uptake of different metal-based NPs, including nanosized metals (silver and gold, both citrate stabilized), metal oxides (copper oxide and titanium dioxide), and CdSe/ZnS core/shell quantum dots at subtoxic concentrations. Specifically, we demonstrated that HSI-M can be used to detect and semi-quantify these NPs in the ciliated protozoan Tetrahymena thermophila as a model aquatic organism. Detection and semi-quantification were achieved on the basis of spectral libraries for the NPs suspended in extracellular substances secreted by this single-celled organism, accounting for matrix effects. HSI-M was able to differentiate between NP types, provided that spectral profiles were significantly different from each other. This difference, in turn, depended upon NP type, size, agglomeration status, and position relative to the focal plane. As an exception among the NPs analyzed in this study, titanium dioxide NPs showed spectral similarities compared to cell material of unexposed control cells, leading to false positives. High biological variability resulted in highly variable uptake of NPs in cells of the same sample as well as between different exposures. We therefore encourage the development of techniques able to reduce the currently long analysis times that still hamper the acquisition of statistically strong data sets. Overall, this study demonstrates the potential and challenges of HSI-M in monitoring cellular uptake of synthetic NPs.

Embedding Pd into SnO2 drastically enhances gas sensing.

Combustion aerosol processes can uniquely embed noble metals into semiconducting particles. Here, monocrystalline SnO2 particles embedded with Pd and/or PdOx were made by flame spray pyrolysis (FSP) of appropriate precursors through microexplosions by droplet-to-particle conversion as the crystal size was proportional to the cube root of precursor solution concentration, C. These particles were air-annealed and leached with nitric acid for removal of metallic Pd from their surface. The SnO2 crystal size varied from 11 to 24 nm and was in close agreement with the primary particle size determined by nitrogen adsorption. The embedded fraction of Pd ranged from about 30 to 80% of the nominal Pd-content. This was achieved by judiciously varying the C, Pd content and the ratio of precursor solution to dispersion oxygen flowrates during FSP. The response of sensors made by doctor blading films of such particles to 1 ppm of acetone and CO was evaluated at 350 °C and 50% relative humidity. Embedding Pd/PdOx into SnO2 significantly increased the sensor response: 2-6 times over that of pure or conventionally-made Pd-containing SnO2 sensors at low nominal Pd-contents (0.2 mol%). For higher ones (i.e. 1 mol% Pd), the sensor response was enhanced by up to two orders of magnitude. This is attributed to Pd atoms in the SnO2 lattice near the particle surface and/or Pd/PdOx clusters acting as nanoelectrodes into SnO2 films and altering their transducing properties as shown by high resolution electron microscopy, XPS and baseline resistance measurements of pure and Pd-embedded SnO2 sensing films.

Material-Intrinsic NIR-Fluorescence Enables Image-Guided Surgery for Ceramic Fracture Removal.

Hip arthroplasty effectively treats advanced osteoarthritis and is therefore entitled as "operation of the 20th century." With demographic shifts, the USA alone is projected to perform up to 850 000 arthroplasties annually by 2030. Many implants now feature a ceramic head, valued for strength and wear resistance. Nonetheless, a fraction, up to 0.03% may fracture during their lifespan, demanding complex removal procedures. To address this, a radiation-free, fluorescence-based image-guided surgical technique is presented. The method uses the inherent fluorescence of ceramic implant materials, demonstrated through chemical and optical analysis of prevalent implant types. Specifically, Biolox delta implants exhibited strong fluorescence around 700 nm with a 74% photoluminescence quantum yield. Emission tails are identified extending into the near-infrared (NIR-I) biological transparency range, forming a vital prerequisite for the label-free visualization of fragments. This ruby-like fluorescence could be attributed to Cr within the zirconia-toughened alumina matrix, enabling the detection of even deep-seated millimeter-sized fragments via camera-assisted techniques. Additionally, fluorescence microscopy allowed detection of µm-sized ceramic particles, enabling debris visualization in synovial fluid as well as histological samples. This label-free optical imaging approach employs readily accessible equipment and can seamlessly transition to clinical settings without significant regulatory barriers, thereby enhancing the safety, efficiency, and minimally invasive nature of fractured ceramic implant removal procedures.

Reusable magnetic mixture of CuFe2O4-Fe2O3 and TiO2 for photocatalytic degradation of pesticides in water.

Photocatalysis is a promising treatment method to remove pollutants from water. TiO2-P25 is a commercially available model photocatalyst, which very efficiently degrades organic pollutants under UVA light exposure. However, the collection and the recovery of TiO2-P25 from cleaned water poses significant difficulties, severely limiting its usability. To address this challenge, we have prepared a sintered mixture of TiO2-P25 nanomaterials and magnetic CuFe2O4-Fe2O3 nanocomposites. The mixture material was shown to contain spinel ferrite, hematite and maghemite structures, copper predominantly in Cu2+ and iron predominantly in Fe3+ state. The CuFe2O4-Fe2O3 and TiO2-P25 mixture demonstrated magnetic collectability from processed water and photocatalytic activity, which was evidenced through the successful photodegradation of the herbicide 2,4-D. Our findings suggest that the sintered mixture of CuFe2O4-Fe2O3 and TiO2-P25 holds a promise for improving photocatalytic water treatment, with the potential to overcome current photocatalyst recovery issues.

Bioglass/ceria nanoparticle hybrids for the treatment of seroma: a comparative long-term study in rats.

Background: Seroma formation is a common postoperative complication. Fibrin-based glues are typically employed in an attempt to seal the cavity. Recently, the first nanoparticle (NP)-based treatment approaches have emerged. Nanoparticle dispersions can be used as tissue glues, capitalizing on a phenomenon known as 'nanobridging'. In this process, macromolecules such as proteins physically adsorb onto the NP surface, leading to macroscopic adhesion. Although significant early seroma reduction has been shown, little is known about long-term efficacy of NPs. The aim of this study was to assess the long-term effects of NPs in reducing seroma formation, and to understand their underlying mechanism. Methods: Seroma was surgically induced bilaterally in 20 Lewis rats. On postoperative day (POD) 7, seromas were aspirated on both sides. In 10 rats, one side was treated with NPs, while the contralateral side received only NP carrier solution. In the other 10 rats, one side was treated with fibrin glue, while the other was left untreated. Seroma fluid, blood and tissue samples were obtained at defined time points. Biochemical, histopathological and immunohistochemical assessments were made. Results: NP-treated sides showed no macroscopically visible seroma formation after application on POD 7, in stark contrast to the fibrin-treated sides, where 60% of the rats had seromas on POD 14, and 50% on POD 21. At the endpoint (POD 42), sides treated with nanoparticles (NPs) exhibited significant macroscopic differences compared to other groups, including the absence of a cavity, and increased fibrous adhesions. Histologically, there were more macrophage groupings and collagen type 1 (COL1) deposits in the superficial capsule on NP-treated sides. Conclusion: NPs not only significantly reduced early manifestations of seroma and demonstrated an anti-inflammatory response, but they also led to increased adhesion formation over the long term, suggesting a decreased risk of seroma recurrence. These findings highlight both the adhesive properties of NPs and their potential for clinical therapy.

Biochemical transformations of inorganic nanomedicines in buffers, cell cultures and organisms.

The field of nanomedicine is rapidly evolving, with new materials and formulations being reported almost daily. In this respect, inorganic and inorganic-organic composite nanomaterials have gained significant attention. However, the use of new materials in clinical trials and their final approval as drugs has been hampered by several challenges, one of which is the complex and difficult to control nanomaterial chemistry that takes place within the body. Several reviews have summarized investigations on inorganic nanomaterial stability in model body fluids, cell cultures, and organisms, focusing on their degradation as well as the influence of corona formation. However, in addition to these aspects, various chemical reactions of nanomaterials, including phase transformation and/or the formation of new/secondary nanomaterials, have been reported. In this review, we discuss recent advances in our understanding of biochemical transformations of medically relevant inorganic (composite) nanomaterials in environments related to their applications. We provide a refined terminology for the primary reaction mechanisms involved to bridge the gaps between different disciplines involved in this research. Furthermore, we highlight suitable analytical techniques that can be harnessed to explore the described reactions. Finally, we highlight opportunities to utilize them for diagnostic and therapeutic purposes and discuss current challenges and research priorities.

Nanoanalytical Insights into the Stability, Intracellular Fate, and Biotransformation of Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) have found increasing applications in the biomedical field due to their unique properties and high modularity. Although the limited stability of MOFs in biological environments is increasingly recognized, analytical techniques have not yet been harnessed to their full potential to assess the biological fate of MOFs. Here, we investigate the environment-dependent biochemical transformations of widely researched nanosized MOFs (nMOFs) under conditions relevant to their medical application. We assess the chemical stability of antimicrobial zinc-based drug delivery nMOFs (Zn-ZIF-8 and Zn-ZIF-8:Ce) and radio-enhancer candidate nMOFs (Hf-DBA, Ti-MIL-125, and TiZr-PCN-415) containing biologically nonessential group IV metal ions. We reveal that even a moderate decrease in pH to values encountered in lysosomes (pH 4.5-5) leads to significant dissolution of ZIF-8 and partial dissolution of Ti-MIL-125, whereas no substantial dissolution was observed for TiZr-PCN-415 and Hf-DBA nMOFs. Exposure to phosphate-rich buffers led to phosphate incorporation in all nMOFs, resulting in amorphization and morphological changes. Interestingly, long-term cell culture studies revealed that nMOF (bio)transformations of, e.g., Ti-MIL-125 were cellular compartment-dependent and that the phosphate content in the nMOF varied significantly between nMOFs localized in lysosomes and those in the cytoplasm. These results illustrate the delicate nature and environment-dependent properties of nMOFs across all stages of their life cycle, including storage, formulation, and application, and the need for in-depth analyses of biotransformations for an improved understanding of structure-function relationships. The findings encourage the considerate choice of suspension buffers for MOFs because these media may lead to significant material alterations prior to application.

Metal-Organic Framework Mediated Radio-Enhancement Assessed in High-Throughput-Compatible 3D Tumor Spheroid Co-Cultures.

Inorganic nanomaterials have gained increasing attention in radiation oncology, owing to their radiation therapy enhancing properties. To accelerate candidate material selection and overcome the disconnect between conventional 2D cell culture and in vivo findings, screening platforms unifying high-throughput with physiologically relevant endpoint analysis based on 3D in vitro models are promising. Here, a 3D tumor spheroid co-culture model based on cancerous and healthy human cells is presented for the concurrent assessment of radio-enhancement efficacy, toxicity, and intratissural biodistribution with full ultrastructural context of radioenhancer candidate materials. Its potential for rapid candidate materials screening is showcased based on the example of nano-sized metal-organic frameworks (nMOFs) and direct benchmarking against gold nanoparticles (the current "gold standard"). Dose enhancement factors (DEFs) ranging between 1.4 and 1.8 are measured for Hf-, Ti-, TiZr-, and Au-based materials in 3D tissues and are overall lower than in 2D cell cultures, where DEF values exceeding 2 are found. In summary, the presented co-cultured tumor spheroid-healthy fibroblast model with tissue-like characteristics may serve as high-throughput platform enabling rapid, cell line-specific endpoint analysis for therapeutic efficacy and toxicity assessment, as well as accelerated radio-enhancer candidate screening.

Multiscale Multimodal Investigation of the Intratissural Biodistribution of Iron Nanotherapeutics with Single Cell Resolution Reveals Co-Localization with Endogenous Iron in Splenic Macrophages.

Imaging of iron-based nanoparticles (NPs) remains challenging because of the presence of endogenous iron in tissues that is difficult to distinguish from exogenous iron originating from the NPs. Here, an analytical cascade for characterizing the biodistribution of biomedically relevant iron-based NPs from the organ scale to the cellular and subcellular scales is introduced. The biodistribution on an organ level is assessed by elemental analysis and quantification of magnetic iron by electron paramagnetic resonance, which allowed differentiation of exogenous and endogenous iron. Complementary to these bulk analysis techniques, correlative whole-slide optical and electron microscopy provided spatially resolved insight into the biodistribution of endo- and exogenous iron accumulation in macrophages, with single-cell and single-particle resolution, revealing coaccumulation of iron NPs with endogenous iron in splenic macrophages. Subsequent transmission electron microscopy revealed two types of morphologically distinct iron-containing structures (exogenous nanoparticles and endogenous ferritin) within membrane-bound vesicles in the cytoplasm, hinting at an attempt of splenic macrophages to extract and recycle iron from exogenous nanoparticles. Overall, this strategy enables the distinction of endo- and exogenous iron across scales (from cm to nm, based on the analysis of thousands of cells) and illustrates distribution on organ, cell, and organelle levels.

X-ray radio-enhancement by Ti3C2Tx MXenes in soft tissue sarcoma.

Radiotherapy is a cornerstone of cancer treatment. However, due to the low tissue specificity of ionizing radiation, damage to the surrounding healthy tissue of the tumor remains a significant challenge. In recent years, radio-enhancers based on inorganic nanomaterials have gained considerable interest. Beyond the widely explored metal and metal oxide nanoparticles, 2D materials, such as MXenes, could present potential benefits because of their inherently large specific surface area. In this study, we highlight the promising radio-enhancement properties of Ti3C2Tx MXenes. We demonstrate that atomically thin layers of titanium carbides (Ti3C2Tx MXenes) are efficiently internalized and well-tolerated by mammalian cells. Contrary to MXenes suspended in aqueous buffers, which fully oxidize within days, yielding rice-grain shaped rutile nanoparticles, the MXenes internalized by cells oxidize at a slower rate. This is consistent with cell-free experiments that have shown slower oxidation rates in cell media and lysosomal buffers compared to dispersants without antioxidants. Importantly, the MXenes exhibit robust radio-enhancement properties, with dose enhancement factors reaching up to 2.5 in human soft tissue sarcoma cells, while showing no toxicity to healthy human fibroblasts. When compared to oxidized MXenes and commercial titanium dioxide nanoparticles, the intact 2D titanium carbide flakes display superior radio-enhancement properties. In summary, our findings offer evidence for the potent radio-enhancement capabilities of Ti3C2Tx MXenes, marking them as a promising candidate for enhancing radiotherapy.

Evaluation of fiber and debris release from protective COVID-19 mask textiles and in vitro acute cytotoxicity effects.

Since the start of the current COVID-19 pandemic, for the first time a significant fraction of the world's population cover their respiratory system for an extended period with mostly medical facemasks and textile masks. This new situation raises questions about the extent of mask related debris (fibers and particles) being released and inhaled and possible adverse effects on human health. This study aimed to quantify the debris release from a textile-based facemask in comparison to a surgical mask and a reference cotton textile using both liquid and air extraction. Under liquid extractions, cotton-based textiles released up to 29'452 ± 1'996 fibers g-1 textile while synthetic textiles released up to 1'030 ± 115 fibers g-1 textile. However, when the masks were subjected to air-based extraction scenarios, only a fraction (0.1-1.1%) of this fiber amount was released. Several metals including copper (up to 40.8 ± 0.9 µg g-1) and iron (up to 7.0 ± 0.3 µg g-1) were detected in acid dissolved textiles. Additionally the acute in vitro toxicity of size-fractionated liquid extracts (below and above 0.4 µm) were assessed on human alveolar basal epithelial cells. The current study shows no acute cytotoxicity response for all the analyzed facemasks.

Cellular fate and performance of group IV metal organic framework radioenhancers.

Nano-sized metal organic frameworks (nanoMOFs) have gained increasing importance in biomedicine due to their tunable properties. In addition to their use as carriers in drug delivery, nanoMOFs containing hafnium have been successfully employed as radio-enhancers augmenting damage caused by X-ray irradiation in tumor tissue. While results are encouraging, there is little mechanistic understanding available, and the biological fate of these radio-enhancer nanoparticles remains largely unexplored. Here, we synthesized a selection of group IV metal-based (Hf, Ti, Ti/Zr) nanoMOFs and investigated their cell compatibility and radio-enhancement performance in direct comparison to the corresponding metal oxides. We report surprising radio-enhancement performance of Ti-containing nanoMOFs reaching dose modifying ratios of 3.84 in human sarcoma cells and no relevant dose modification in healthy human fibroblasts. These Ti-based nanoMOFs even outperformed previously reported Hf-based nanoMOFs as well as equimolar group IV metal oxides in direct benchmarking experiments. While group IV nanoMOFs were well-tolerated by cells in the absence of irradiation, the nanoMOFs partially dissolved in lysosomal buffer conditions showing distinctly different chemical stability compared to widely researched group IV oxides (TiO2, ZrO2, and HfO2). Taken together, this study illustrates the promising potential of Ti-based nanoMOFs for radio-enhancement and provides insight into the intracellular fate and stability of group IV nanoMOFs.

Antibiofilm activity of nanosilver coatings against Staphylococcus aureus.

Implant infections due to bacterial biofilms constitute a major healthcare challenge today. One way to address this clinical need is to modify the implant surface with an antimicrobial nanomaterial. Among such nanomaterials, nanosilver is arguably the most powerful one, due to its strong and broad antimicrobial activity. However, there is still a lack of understanding on how physicochemical characteristics of nanosilver coatings affect their antibiofilm activity. More specifically, the contributions of silver (Ag)+ ion-mediated vs. contact-based mechanisms to the observed antimicrobial activity are yet to be elucidated. To address this knowledge gap, we produce here nanosilver coatings on substrates by flame aerosol direct deposition that allows for facile control of the coating composition and Ag particle size. We systematically study the effect of (i) nanosilver content in composite Ag silica (SiO2) coatings from 0 (pure SiO2) up to 50 wt%, (ii) the Ag particle size and (iii) the coating thickness on the antibiofilm activity against Staphylococcus aureus (S. aureus), a clinically-relevant pathogen often present on the surface of surgically-installed implants. We show that the Ag+ ion concentration in solution largely drives the observed antibiofilm effect independently of Ag size and coating thickness. Furthermore, co-incubation of both pure SiO2 and nanosilver coatings in the same well also reveals that the antibiofilm effect stems predominantly from the released Ag+ ions, which is especially pronounced for coatings featuring the smallest Ag particle sizes, rather than direct bacterial contact inhibition. We also examine the biocompatibility of the developed nanosilver coatings in terms of pre-osteoblastic cell viability and proliferation, comparing it to that of pure SiO2. This study lays the foundation for the rational design of nanosilver-based antibiofilm implant coatings.