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.

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.

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.

Prospects of nanoparticle-based radioenhancement for radiotherapy.

Radiotherapy is a key pillar of solid cancer treatment. Despite a high level of conformal dose deposition, radiotherapy is limited due to co-irradiation of organs at risk and subsequent normal tissue toxicities. Nanotechnology offers an attractive opportunity for increasing the efficacy and safety of cancer radiotherapy. Leveraging the freedom of design and the growing synthetic capabilities of the nanomaterial-community, a variety of engineered nanomaterials have been designed and investigated as radiosensitizers or radioenhancers. While research so far has been primarily focused on gold nanoparticles and other high atomic number materials to increase the absorption cross section of tumor tissue, recent studies are challenging the traditional concept of high-Z nanoparticle radioenhancers and highlight the importance of catalytic activity. This review provides a concise overview on the knowledge of nanoparticle radioenhancement mechanisms and their quantification. It critically discusses potential radioenhancer candidate materials and general design criteria for different radiation therapy modalities, and concludes with research priorities in order to advance the development of nanomaterials, to enhance the efficacy of radiotherapy and to increase at the same time the therapeutic window.

Nanothermometry-Enabled Intelligent Laser Tissue Soldering.

While often life-saving, surgical resectioning of diseased tissues puts patients at risk for post-operative complications. Sutures and staples are well-accepted and routinely used to reconnect tissues, however, their mechanical mismatch with biological soft tissue and invasiveness contribute to wound healing complications, infections, and post-operative fluid leakage. In principle, laser tissue soldering offers an attractive, minimally-invasive alternative for seamless soft tissue fusion. However, despite encouraging experimental observations, including accelerated healing and lowered infection risk, critical issues related to temperature monitoring and control during soldering and associated complications have prevented their clinical exploitation to date. Here, intelligent laser tissue soldering (iSoldering) with integrated nanothermometry is introduced as a promising yet unexplored approach to overcome the critical shortcomings of laser tissue soldering. It demonstrates that adding thermoplasmonic and nanothermometry nanoparticles to proteinaceous solders enables heat confinement and non-invasive temperature monitoring and control, offering a route to high-performance, leak-tight tissue sealing even at deep tissue sites. The resulting tissue seals exhibit excellent mechanical properties and resistance to chemically-aggressive digestive fluids, including gastrointestinal juice. The iSolder can be readily cut and shaped by surgeons to optimally fit the tissue defect and can even be applied using infrared light from a medically approved light source, hence fulfilling key prerequisites for application in the operating theatre. Overall, iSoldering enables reproducible and well-controlled high-performance tissue sealing, offering new prospects for its clinical exploitation in diverse fields ranging from cardiovascular to visceral and plastic surgery.

Multiscale multimodal characterization and simulation of structural alterations in failed bioprosthetic heart valves.

Calcific degeneration is the most frequent type of heart valve failure, with rising incidence due to the ageing population. The gold standard treatment to date is valve replacement. Unfortunately, calcification oftentimes re-occurs in bioprosthetic substitutes, with the governing processes remaining poorly understood. Here, we present a multiscale, multimodal analysis of disturbances and extensive mineralisation of the collagen network in failed bioprosthetic bovine pericardium valve explants with full histoanatomical context. In addition to highly abundant mineralized collagen fibres and fibrils, calcified micron-sized particles previously discovered in native valves were also prevalent on the aortic as well as the ventricular surface of bioprosthetic valves. The two mineral types (fibres and particles) were detectable even in early-stage mineralisation, prior to any macroscopic calcification. Based on multiscale multimodal characterisation and high-fidelity simulations, we demonstrate that mineral occurrence coincides with regions exposed to high haemodynamic and biomechanical indicators. These insights obtained by multiscale analysis of failed bioprosthetic valves serve as groundwork for the evidence-based development of more durable alternatives. STATEMENT OF SIGNIFICANCE: Bioprosthetic valve calcification is a well-known clinically significant phenomenon, leading to valve failure. The nanoanalytical characterisation of bioprosthetic valves gives insights into the highly abundant, extensive calcification and disorganization of the collagen network and the presence of calcium phosphate particles previously reported in native cardiovascular tissues. While the collagen matrix mineralisation can be primarily attributed to a combination of chemical and mechanical alterations, the calcified particles are likely of host cellular origin. This work presents a straightforward route to mineral identification and characterization at high resolution and sensitivity, and with full histoanatomical context and correlation to hemodynamic and biomechanical indicators, hence providing design cues for improved bioprosthetic valve alternatives.

Surgical Sealant with Integrated Shape-Morphing Dual Modality Ultrasound and Computed Tomography Sensors for Gastric Leak Detection.

Postoperative anastomotic leaks are the most feared complications after gastric surgery. For diagnostics clinicians mostly rely on clinical symptoms such as fever and tachycardia, often developing as a result of an already fully developed, i.e., symptomatic, surgical leak. A gastric fluid responsive, dual modality, electronic-free, leak sensor system integrable into surgical adhesive suture support materials is introduced. Leak sensors contain high atomic number carbonates embedded in a polyacrylamide matrix, that upon exposure to gastric fluid convert into gaseous carbon dioxide (CO2 ). CO2 bubbles remain entrapped in the hydrogel matrix, leading to a distinctly increased echogenic contrast detectable by a low-cost and portable ultrasound transducer, while the dissolution of the carbonate species and the resulting diffusion of the cation produces a markedly reduced contrast in computed tomography imaging. The sensing elements can be patterned into a variety of characteristic shapes and can be combined with nonreactive tantalum oxide reference elements, allowing the design of shape-morphing sensing elements visible to the naked eye as well as artificial intelligence-assisted automated detection. In summary, shape-morphing dual modality sensors for the early and robust detection of postoperative complications at deep tissue sites, opening new routes for postoperative patient surveillance using existing hospital infrastructure is reported.

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.

Magnetic blood purification-based soluble fms-like tyrosine kinase-1 removal in comparison with dextran sulfate apheresis and therapeutic plasma exchange.

BACKGROUND: Preeclampsia remains one of the most serious complications of pregnancy. Effective therapies are yet to be developed. Recent research has identified an imbalance of angiogenic and antiangiogenic factors as a root cause of preeclampsia. In particular, soluble fms-like tyrosine kinase-1 (sFlt-1) has been shown to bind the angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), reducing blood vessel growth. Increasing preclinical and clinical evidence suggests that removal of the sFlt-1 protein may benefit patients with early onset preeclampsia. sFlt-1 may be removed by conventional blood purification techniques, such as therapeutic plasma exchange (TPE) and dextran sulfate apheresis (DSA), or emerging technologies, including extracorporeal magnetic blood purification (MBP). METHODS: We compare the performance and selectivity of TPE, DSA, and MBP for the therapeutic removal of sFlt-1. For MPB, we employ magnetic nanoparticles functionalized with either sFlt-1 antibodies or the sFlt-1-binding partner, vascular endothelial growth factor (VEGF). RESULTS: We demonstrate that sFlt-1 removal by MBP is feasible and significantly more selective than TPE and DSA at comparable sFlt-1 removal efficiencies (MBP 96%, TPE 92%, DSA 78%). During both TPE and DSA, complement factors (incl. C3c and C4) are depleted to a considerable extent (-90% for TPE, -55% for DSA), while in MBP, complement factor concentrations remain unaltered. We further demonstrate that the removal efficacy of sFlt-1 in the MBP approach is strongly dependent on the nanoparticle type and dose and can be optimized to reach clinically feasible throughputs. CONCLUSIONS: Taken together, the highly selective removal of sFlt-1 and potential other disease-causing factors by extracorporeal magnetic blood purification may offer new prospects for preeclamptic patients.

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.

Modular stimuli-responsive hydrogel sealants for early gastrointestinal leak detection and containment.

Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of cases. Currently, surgeons rely on the monitoring of surrogate markers and clinical symptoms, which often lack sensitivity and specificity, hence only offering late-stage detection of fully developed leaks. Here, we present a holistic solution in the form of a modular, intelligent suture support sealant patch capable of containing and detecting leaks early. The pH and/or enzyme-responsive triggerable sensing elements can be read out by point-of-need ultrasound imaging. We demonstrate reliable detection of the breaching of sutures, in as little as 3 hours in intestinal leak scenarios and 15 minutes in gastric leak conditions. This technology paves the way for next-generation suture support materials that seal and offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables.

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.

Catalytic activity imperative for nanoparticle dose enhancement in photon and proton therapy.

Nanoparticle-based radioenhancement is a promising strategy for extending the therapeutic ratio of radiotherapy. While (pre)clinical results are encouraging, sound mechanistic understanding of nanoparticle radioenhancement, especially the effects of nanomaterial selection and irradiation conditions, has yet to be achieved. Here, we investigate the radioenhancement mechanisms of selected metal oxide nanomaterials (including SiO2, TiO2, WO3 and HfO2), TiN and Au nanoparticles for radiotherapy utilizing photons (150 kVp and 6 MV) and 100 MeV protons. While Au nanoparticles show outstanding radioenhancement properties in kV irradiation settings, where the photoelectric effect is dominant, these properties are attenuated to baseline levels for clinically more relevant irradiation with MV photons and protons. In contrast, HfO2 nanoparticles retain some of their radioenhancement properties in MV photon and proton therapies. Interestingly, TiO2 nanoparticles, which have a comparatively low effective atomic number, show significant radioenhancement efficacies in all three irradiation settings, which can be attributed to the strong radiocatalytic activity of TiO2, leading to the formation of hydroxyl radicals, and nuclear interactions with protons. Taken together, our data enable the extraction of general design criteria for nanoparticle radioenhancers for different treatment modalities, paving the way to performance-optimized nanotherapeutics for precision radiotherapy.

Assessment of iron nanoparticle distribution in mouse models using ultrashort-echo-time MRI.

Microscopic magnetic field inhomogeneities caused by iron deposition or tissue-air interfaces may result in rapid decay of transverse magnetization in MRI. The aim of this study is to detect and quantify the distribution of iron-based nanoparticles in mouse models by applying ultrashort-echo-time (UTE) sequences in tissues exhibiting extremely fast transverse relaxation. In 24 C57BL/6 mice (two controls), suspensions containing either non-oxidic Fe or AuFeOx nanoparticles were injected into the tail vein at two doses (200 µg and 600 µg per mouse). Mice underwent MRI using a UTE sequence at 4.7 T field strength with five different echo times between 100 µs and 5000 µs. Transverse relaxation times T2 * were computed for the lung, liver, and spleen by mono-exponential fitting. In UTE imaging, the MRI signal could reliably be detected even in liver parenchyma exhibiting the highest deposition of nanoparticles. In animals treated with Fe nanoparticles (600 µg per mouse), the relaxation time substantially decreased in the liver (3418 ± 1534 µs (control) versus 228 ± 67 µs), the spleen (2170 ± 728 µs versus 299 ± 97 µs), and the lungs (663 ± 101 µs versus 413 ± 99 µs). The change in transverse relaxation was dependent on the number and composition of the nanoparticles. By pixel-wise curve fitting, T2 * maps were calculated showing nanoparticle distribution. In conclusion, UTE sequences may be used to assess and quantify nanoparticle distribution in tissues exhibiting ultrafast signal decay in MRI.

Inorganic nanohybrids combat antibiotic-resistant bacteria hiding within human macrophages.

Bacterial infections are one of the main health concerns humanity faces today and bacterial resistances and protection mechanisms are set to aggravate the issue in the coming years. An increasing number of bacterial strains evades antibiotic treatment by hiding inside cells. Conventional antimicrobial agents are unable to penetrate or be retained in the infected mammalian cells. Recent approaches to overcome these limitations have focused on load-carrier systems, requiring a triggered discharge leading to complex release kinetics. The unison of potent antimicrobial activity with high mammalian cell compatibility is a prerequisite for intracellular activity, which is not well-met by otherwise well-established inorganic systems, such as silver-based nanoparticles. In this work, load and carrier are combined into one functional inorganic nanoparticle system, which unites antimicrobial activity with mammalian cell compatibility. These multicomponent nanohybrids based on cerium oxide are produced in one step, yet unite complex materials. The nanoparticles form suprastructures of similar size and surface charge as bacteria, therefore facilitating the uptake into the same subcellular compartments, where they unleash their antibacterial effect. Such intrinsically antibacterial nanohybrids significantly reduce bacterial survival inside macrophages without harming the latter. Furthermore, blocking of nanoparticle endocytosis and subcellular electron microscopy elucidate the mechanism of action. Taken together, this work presents the first demonstration of antibacterial activity of ceria-based nanoparticles inside of mammalian cells and offers a route to straightforward and robust intracellular antibacterial agents that do not depend on payload delivery or biological constituents.

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.

Simultaneous Nanothermometry and Deep-Tissue Imaging.

Bright, stable, and biocompatible fluorescent contrast agents operating in the second biological window (1000-1350 nm) are attractive for imaging of deep-lying structures (e.g., tumors) within tissues. Ideally, these contrast agents also provide functional insights, such as information on local temperature. Here, water-dispersible barium phosphate nanoparticles doped with Mn5+ are made by scalable, continuous, and sterile flame aerosol technology and explored as fluorescent contrast agents with temperature-sensitive peak emission in the NIR-II (1190 nm). Detailed assessment of their stability, toxicity with three representative cell lines (HeLa, THP-1, NHDF), and deep-tissue imaging down to about 3 cm are presented. In addition, their high quantum yield (up to 34%) combined with excellent temperature sensitivity paves the way for concurrent deep-tissue imaging and nanothermometry, with biologically well-tolerated nanoparticles.

Uptake, distribution and radio-enhancement effects of gold nanoparticles in tumor microtissues.

Radiotherapy is an integral and highly effective part of cancer therapy, applicable in over 50% of patients affected by cancer. Due to the low specificity of the X-ray irradiation, the maximal radiation dose is greatly limited in order to avoid damage to surrounding healthy tissue. The limitations in applicable dose oftentimes result in the survival of a subpopulation of radio-resistant cells that then cause cancer reoccurence. Approaches based on tumor-targeted high atomic number inorganic nanoparticles have been proposed to locally increase the photoelectric absorption cross-section of tumors relative to healthy tissue. However, the complex interplay between the nanoparticle radio-enhancers and the tumor tissue has led to poor translation of in vitro findings to (pre)clinics. Here, we report the development of a tumor microtissue model along with analytical imaging for the quantitative assessment of nanoparticle-based radio-enhancement as a function of nanoparticle size, uptake and intratissural distribution. The advanced in vitro model exhibits key features of cancerous tissues, including diminished susceptibility to drugs and attenuated response to nanoparticle treatment compared to corresponding conventional 2D cell cultures. Whereas radio-enhancement effects between 2D and 3D cell cultures were comparable for 5 nm gold particles, the limited penetration of 50 nm gold nanoparticles into 3D microtissues led to a significantly reduced radio-enhancement effect in 3D compared to 2D. Taken together, tumor microtissues, which in stark contrast to 2D cell culture exhibit tissue-like features, may provide a valuable high-throughput intermediate pre-selection step in the preclinical translation of nanoparticle-based radio-enhancement therapy designs.

Supramolecular Insights into Domino Effects of Ag@ZnO-Induced Oxidative Stress in Melanoma Cancer Cells.

Recent studies suggest that cancer cell death accompanied by organelle dysfunction might be a promising approach for cancer therapy. The Golgi apparatus has a key role in cell function and may initiate signaling pathways to mitigate stress and, if irreparable, start apoptosis. It has been shown that Golgi disassembly and fragmentation under oxidative stress act as indicators for stress-mediated cell death pathways through cell cycle arrest in the G2/M phase. The present study shows that UV-induced reactive oxygen species (ROS) generation by Ag@ZnO nanoparticles (NPs) transform the Golgi structures from compressed perinuclear ribbons into detached vesicle-like structures distributed in the entire cytoplasm of melanoma cells. This study also demonstrates that Ag@ZnO NP-induced Golgi fragmentation cooccurs with G2 block of cell cycle progression, preventing cells from entering the mitosis phase. Additionally, the increased intracellular ROS production triggered by Ag@ZnO NPs upon UV exposure promoted autophagy. Taken together, Ag@ZnO NPs induce stress-related Golgi fragmentation and autophagy, finally leading to melanoma cell apoptosis. Intracellular oxidative stress generated by Ag@ZnO NPs upon UV irradiation may thus represent a targeted approach to induce cancer cell death through organelle destruction in melanoma cells, while fibroblast cells remained largely unaffected.

Engineering the Bioactivity of Flame-Made Ceria and Ceria/Bioglass Hybrid Nanoparticles.

Despite its use as a highly efficient and reusable catalyst in research and industrial settings, cerium oxide nanoparticles or nanoceria have yet to gain a foothold in the biomedical field. A variety of beneficial effects of nanoceria have been demonstrated, including its use as an inorganic nanoenzyme to mimic antioxidant enzymes, to protect mammalian cells, and to suppress microbial growth. While these properties are of high interest for wound-management applications, the literature offers contradicting reports on toxicity and enzymatic activity of nanoceria. These discrepancies can be attributed to differences between synthesis methods and insufficient physicochemical characterization, leading to incomparable studies. The activity of nanoceria is mostly governed by its Ce3+/Ce4+ ratio which needs to be controlled to compare different nanoceria systems. In this work, we demonstrate that liquid-feed flame spray pyrolysis offers excellent control over the oxidation state in a one-step synthesis of nanoceria. This control allows a comprehensive comparison of different types of ceria nanoparticles. We connect physicochemical characteristics to biomedically relevant properties such as superoxide dismutase and catalase mimicry, human monocyte and macrophage protection, and antimicrobial activity. Furthermore, we demonstrate how the synthesis method also allows tailoring the properties of ceria/bioglass hybrid nanoparticles, thus creating nanoparticles with manifold biomedical prospects.