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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 SiO 2 , TiO 2 , WO 3 and HfO 2 ), 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, HfO 2 nanoparticles retain some of their radioenhancement properties in MV photon and proton therapies. Interestingly, TiO 2 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 TiO 2 , 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. Nanoparticles have recently received attention in radiation therapy since they can act as radioenhancers. In this article, the authors report on the dose enhancement capabilities of a series of nanoparticles based on their metal core composition and beam characteristics, obtaining designing criteria for their optimal performance in specific radiotreatments.

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. Digestive surgical leaks manifesting days after a successful surgery can lead to severe complications and affect healthcare worldwide. Here, the authors address the problem holistically with a hydrogel patch capable of sealing tissues, while detecting imminent leaks via a smartphone-operated ultrasound probe.

Wound care and soft tissue repair have been a major human concern for millennia. Despite considerable advancements in standards of living and medical abilities, difficult-to-heal wounds remain a major burden for patients, clinicians and the healthcare system alike. Due to an aging population, the rise in chronic diseases such as vascular disease and diabetes, and the increased incidence of antibiotic resistance, the problem is set to worsen. The global wound care market is constantly evolving and expanding, and has yielded a plethora of potential solutions to treat poorly healing wounds. In ancient times, before such a market existed, metals and their ions were frequently used in wound care. In combination with plant extracts, they were used to accelerate the healing of burns, cuts and combat wounds. With the rise of organic chemistry and small molecule drugs and ointments, researchers lost their interest in inorganic materials. Only recently, the advent of nano-engineering has given us a toolbox to develop inorganic materials on a length-scale that is relevant to wound healing processes. The robustness of synthesis, as well as the stability and versatility of inorganic nanotherapeutics gives them potential advantages over small molecule drugs. Both bottom-up and top-down approaches have yielded functional inorganic nanomaterials, some of which unite the wound healing properties of two or more materials. Furthermore, these nanomaterials do not only serve as the active agent, but also as the delivery vehicle, and sometimes as a scaffold. This review article provides an overview of inorganic hybrid nanotherapeutics with promising properties for the wound care field. These therapeutics include combinations of different metals, metal oxides and metal ions. Their production, mechanism of action and applicability will be discussed in comparison to conventional wound healing products.

The pain‐free monitoring of blood‐based biomarkers is essential for early detection of diseases like cancers, infections, and metabolic disorders such as diabetes. While research often focuses on venous blood analysis, menstruation blood is an overlooked but promising source. Evidence shows a strong correlation between biomarker levels in menstruation and venous blood for many clinical analytes. A wearable, microfluidic monitoring platform integrated into hygiene pads is presented for electronic‐free, naked‐eye detection of disease biomarkers in menstruation blood (MenstruAI). Semi‐quantitative detection of C‐reactive protein (CRP), cancer biomarkers carcinoembryonic antigen (CEA) and cancer antigen 125 (CA‐125), and endometriosis biomarker CA‐125 is demonstrated. The biomarker‐induced color changes can be read by the naked eye or a smartphone app with a machine‐learning algorithm for semi‐quantitative analysis. MenstruAI can revolutionize women's health by offering a non‐invasive, affordable, and accessible health monitoring method, democratizing healthcare, and enhancing service availability and equity. MenstruAI integrates a paper‐based biosensor into sanitary pads to detect biomarkers in menstrual blood, enabling accessible, lab‐free diagnostics health. The platform supports early disease detection, especially in underserved communities, while challenging menstrual stigma and opening pathways for scalable, inclusive, and sustainable population health screening through wearable technologies.

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. Non‐toxic Mn5+‐doped Ba3(PO4)2 nanoparticles smaller than 100 nm are prepared by scalable flame aerosol technology exhibiting ultrabright fluorescence in the preferred spectral region for bioimaging above 1000 nm. They can serve also as nanothermometers within tissues by capitalizing on their temperature‐dependent emission with high quantum yields. The nanoparticle stability, biocompatibility and deep‐tissue imaging down to about 3 cm are elucidated.

Anastomotic leakage (AL) is the leaking of non‐sterile gastrointestinal contents into a patient's abdominal cavity. AL is one of the most dreaded complications following gastrointestinal surgery, with mortality rates reaching up to 27%. The current diagnostic methods for anastomotic leaks are limited in sensitivity and specificity. Since the timing of detection directly impacts patient outcomes, developing new, fast, and simple methods for early leak detection is crucial. Here, a naked eye‐readable, electronic‐free macromolecular network drain fluid sensor is introduced for continuous monitoring and early detection of AL at the patient's bedside. The sensor array comprises three different macromolecular network sensing elements, each tailored for selectivity toward the three major digestive enzymes found in the drainage fluid during a developing AL. Upon digestion of the macromolecular network structure by the respective digestive enzymes, the sensor produces an optical shift discernible to the naked eye. The diagnostic efficacy and clinical applicability of these sensors are demonstrated using clinical samples from 32 patients, yielding a Receiver Operating Characteristic Area Under the Curve (ROC AUC) of 1.0. This work has the potential to significantly contribute to improved patient outcomes through continuous monitoring and early, low‐cost, and reliable AL detection. Anastomotic leakage (AL) is the leaking of pathogenic, non‐sterile gastrointestinal contents into the abdominal cavity of a patient, with mortality rates of up to 27%. In this work, a naked eye‐readable, electronic‐free sensor for the continuous monitoring of drain fluid enzymes and early detection of AL is introduced.

Nanoparticle radioenhancement offers a promising strategy for augmenting radiotherapy by locally increasing radiation damage to tumor tissue. While past research has predominantly focused on nanomaterials with high atomic numbers, such as Au and HfO2, recent work has revealed that their radioenhancement efficacy decreases considerably when using clinically relevant megavoltage X‐rays as opposed to the orthovoltage X‐rays typically employed in research settings. Here, radiocatalytically active Ti‐based nanomaterials for clinical X‐ray therapy settings are designed. A range of candidate materials, including TiO2 (optionally decorated with Ag or Pt nanoseeds), Ti‐containing metal–organic frameworks (MOFs), and 2D Ti‐based carbides known as Ti3C2Tx MXenes, is investigated. It is demonstrated that these titanium‐based candidates remain consistently performant across a wide energy spectrum, from orthovoltage to megavoltage. This sustained performance is attributed to the catalytic generation of reactive oxygen species, moving beyond the simple physical dose enhancements associated with photoelectric effects. Beyond titania, emergent materials like titanium‐based MOFs and MXenes exhibit encouraging results, achieving dose‐enhancement factors of up to three in human soft tissue sarcoma cells. Notably, these enhancements are absent in healthy human fibroblast cells under similar conditions of particle uptake, underscoring the selective impact of titanium‐based materials in augmenting radiotherapy across the clinically relevant spectral range. Ti‐based radiocatalytic nanomaterials, including MXenes, metal–organic frameworks and inorganic metal oxides, are explored for their potential to enhance X‐ray therapy and compared to traditionally used high‐Z nanoparticles. The radioenhancement efficacies are quantified based on metal uptake in fibrosarcoma cancer cells and mechanisms are studied using acellular 2′,7′‐dichlorofluorescein and in vitro DMSO radical quenching as well as DNA damage assays.

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. Gastric leaks are a greatly feared postsurgical complication. Here dual modality ultrasound and computed tomography sensors for early gastric leak detection is presented. The electronic‐free sensors are fully integrable into adhesive surgical sealant patches as well as patternable, achieving shape morphing contrast changes under conditions of leak, therefore allowing for facile leak diagnostics.

Movement is a key characteristic of higher organisms. During mammalian embryogenesis fetal movements have been found critical to normal tissue development. On the single cell level, however, our current understanding of stem cell differentiation concentrates on inducing factors through cytokine mediated biochemical signaling. In this study, human mesenchymal stem cells and chondrogenesis were investigated as representative examples. We show that pressureless, soft mechanical stimulation precipitated by the cyclic deformation of soft, magnetic hydrogel scaffolds with an external magnetic field, can induce chondrogenesis in mesenchymal stem cells without any additional chondrogenesis transcription factors (TGF-β1 and dexamethasone). A systematic study on the role of movement frequency revealed a classical dose-response relationship for human mesenchymal stem cells differentiation towards cartilage using mere mechanical stimulation. This effect could even be synergistically amplified when exogenous chondrogenic factors and movement were combined.

New possibilities offered by Magnetic Particle Spectroscopy (MPS) and Imaging (MPI) are increasingly being recognized and may accelerate the introduction of MPI into clinical settings. As MPI is a tracer‐based imaging method, the design and development of responsive tracers for functional imaging are particularly appealing. Here, Mn‐ferrite (MnxFe3‐xO4) nanoparticles with finely tuned magnetic properties and enzyme‐like capabilities are reported as potential multifunctional theranostic agents. By adjusting the Mn content in the iron oxide matrix, the magnetic particle imaging signal of different tracers can be tweaked, allowing for the simultaneous quantitative detection of two different tracers in a multi‐color approach. The Mn2FeO4 tracers exhibit potent enzyme‐like catalytic properties, enabling degradation of reactive oxygen species, including H2O2 and OH−. Due to the readily interchangeable oxidation states of Mn and Fe atoms in the crystal structure, a strong dependence of the magnetic properties is observed on H2O2 exposure, which can be exploited for sensing. This enables, for the first time, the sensing of reactive oxygen species based on magnetic particle spectroscopy and imaging, with sensitivity down to 25 µm H2O2 and complete sensor recovery over time. In summary, Mn‐ferrite nanoparticles hold promising potential for imaging, sensing, and degradation of disease‐relevant reactive oxygen species. Magnetic particle spectroscopy and imaging represent promising tools, particularly when combined with manganese‐ferrite nanoparticles as versatile theranostic agents. Adjusting the manganese content allows for simultaneous multi‐color tracer detection and reactive oxygen species sensing via magnetic particle spectroscopy and imaging, creating new opportunities for enhanced imaging capabilities, precise diagnostics, and targeted therapeutic interventions.