Search Results (444)

The morphology of solid surfaces encodes fundamental information about the physical mechanisms that govern their formation. Here, we reinterpret scanning electron microscopy (SEM) micrographs of oxide thin films as two-dimensional self-affine morphology fields (not height-metrology) and analyze them using a multiscale statistical-physics framework that integrates spectral, multifractal, geometric, and topological descriptors. Fourier-based power spectral density (PSD) provides the spectral slope $\beta$ and apparent Hurst exponent $H$, while multifractal scaling yields the information dimensions $D_q$, the singularity spectrum $f\left(\alpha \right)$, and its width $\mathsf{\Delta }\alpha$, which quantify scale hierarchy and intermittency. Lacunarity captures intermediate-scale heterogeneity, and Minkowski functionals—especially the Euler characteristic $\chi \left(\theta \right)$—probe connectivity and identify the onset of a percolation-like network structure. Two representative surfaces with contrasting morphologies are used as model systems: one exhibiting an anisotropic, porous, strongly multifractal structure with fragmented domains; the other showing a compact, nearly isotropic, and nearly monofractal organization. The porous surface/topography displays steep PSD decay, broad multifractal spectra, and positive $\chi$, consistent with a sub-percolated, diffusion-limited, Edwards–Wilkinson-like (EW-like) growth regime. Conversely, the compact surface/topography exhibits gentler spectral slopes, narrower $f\left(\alpha \right)$, enhanced lacunarity at intermediate scales, and a $\chi \left(\theta \right)$ zero-crossing indicative of a connectivity transition where a surface becomes a percolating network, consistent with a Kardar–Parisi–Zhang-like (KPZ-like) correlated growth regime. These results demonstrate that individual SEM micrographs encode quantitative fingerprints of nonequilibrium universality classes and topology-driven transitions from fragmented surfaces to connected networks, showing that SEM intensity maps can serve as a quantitative probe for testing theories of rough surfaces and kinetic growth in experimental thin-film systems. Full article

Human carboxylesterases (CES) are enzymes that play a central role in the metabolism and biotransformation of diverse endogenous substances and xenobiotics. The two most relevant isoforms, CES1 and CES2, are crucial in clinical pharmacotherapy as they catalyze the hydrolysis of numerous approved drugs and prodrugs. Elucidating the structural basis of CES isoform substrate specificity is essential not only for understanding and anticipating the biological fate of administered drugs, but also for designing prodrugs with optimized site-specific bioactivation. Additionally, this knowledge is also important for the design of biomedically useful molecules such as subtype-targeted CES inhibitors and fluorescent probes. In this context, both experimental and computational methodologies have been used to explore the mechanistic and thermodynamic properties of CES-mediated catalysis. Experimental designs commonly employ recombinant CES or human tissue microsomes as enzyme sources, utilizing quantification methods such as spectrophotometry (UV and fluorescence) and mass spectrometry. Computational approaches fall into two categories: (1) modeling substrate: CES recognition and affinity (molecular docking, molecular dynamics simulation, and free-energy binding calculations), and (2) modeling substrate: CES reaction coordinates (hybrid QM/MM simulations). While experimental and theoretical approaches are highly synergistic in studying the catalytic properties of CES subtypes, they represent distinct technical and scientific fields. This review aims to provide an integrated discussion of the key concepts and the interplay between the most commonly used wet-lab and dry-lab strategies for investigating CES catalytic activity. We hope this report will serve as a concise resource for researchers exploring CES isoform specificity, enabling them to effectively utilize both experimental and computational methods. Full article

The detection of single-nucleotide variants (SNVs) is an important challenge in modern genomics, with broad applications in medicine, diagnostics, and agricultural biotechnology. Current detection approaches include PCR-based techniques with high-affinity probes, ligase-based strategies, and sequencing approaches, each with varying degrees of sensitivity, specificity, and practicality. Despite advances in SNV analysis in the medical field, their implementation in the official control and monitoring of genetically modified organisms (GMOs) remains limited. This challenge has gained priority with the advent of new genomic techniques (NGTs), such as CRISPR-Cas nucleases, which allow precise genome editing, including subtle changes at the nucleotide level without introducing foreign DNA. Therefore, traditional methods of GMO detection targeting transgene sequences may not be sufficient to monitor such GMOs. In the European Union, GMO legislation requires distinguishing between conventionally bred and genetically modified plants. The planned introduction of new regulatory categories of NGT plants (NGT1 and NGT2) with different surveillance requirements emphasizes the need for robust, sensitive, and cost-effective SNV detection methods suitable for distinguishing between GMOs, particularly in the context of food and feed safety, traceability, and compliance. Full article

Metal nanoparticles (NP) are increasingly used in biomedical applications. Among them, silver NPs (AgNPs) are used as active components in antibacterial coatings for wound dressings, medical devices, implants, cosmetics, textiles, and food packaging. On the other hand, AgNPs can be toxic to humans, depending on the dose and route of exposure, as agents delivering silver to cells. The cysteine residues are the primary molecular targets in such exposures, due to the high affinity of Ag⁺ ions to thiol groups. The Endothelial monocyte-activating polypeptide II (EMAP II), a cleaved C-terminal peptide of the intracellular aminoacyl-tRNA synthetase multifunctional protein AIMP1, contains five cysteines exposed at its surface. This prompted the question of whether they can be targeted by Ag⁺ ions present at the AgNPs surface or released from AgNPs in the course of oxidative metabolism of the cell. We explored the interactions between recombinant EMAP II, tRNA, and AgNPs using UV-Vis and fluorescence spectroscopy, providing insight into the effects of AgNPs dissolution kinetics on interaction EMAP II with tRNA. In addition, the EMAP II fragments binding to intact AgNPs were established by heteronuclear ¹H-¹⁵N HSQC spectra utilizing a paramagnetic probe. Structural analysis of the EMAP II reveal that the 3D structure of protein was destabilized (partially denatured) by the binding of Ag⁺ ions released from AgNPs at the most exposed cysteines. Surprisingly, this effect enhanced tRNA affinity to EMAP II, lowering its $K_d$. The course of the EMAP II/tRNA/AgNP reaction was also modulated by other factors, such as the presence of Mg²⁺ ions and TCEP, a thiol-group protector used to mimic the reducing conditions of the cell. Full article

Shiga toxin-producing Escherichia coli (STEC) is a major foodborne pathogen, responsible for severe gastrointestinal disease and hemolytic uremic syndrome (HUS). Here, we report Click Detect, a novel diagnostic platform that leverages click display to efficiently produce sensing probes for sandwich-style antigen detection. Click display is an in vitro protein display technology that generates uniform and covalently linked protein–cDNA conjugates in a simple one-pot reaction format within 2 h. The captured sensing probe can be quantified by standard nucleic acid amplification assays. Using click displayed DARPin (D_#20) as the sensing probe and a high-affinity nanobody (N_G1) as the capture reagent, Click Detect reliably detected Shiga toxin 2 (Stx2) at 600 fM by quantitative PCR (qPCR) and 6 pM by loop-mediated isothermal amplification (LAMP). The assay maintained comparable sensitivity in matrices containing up to 40% public swimming pool water or lettuce extract, highlighting robustness for real-world surveillance applications. Key advantages of Click Detect include simple, rapid, and cost-effective (~USD 0.04 per assay) sensing probe preparation, as well as a versatile plug-and-play probe format for detecting other targets. We believe that Click Detect has great potential as a novel sensing platform for food/environmental monitoring and point-of-care diagnostics, with potentially broad applicability to other toxins and protein targets. Full article

The osmium(II) polypyridyl complex [Os(tpy)(pydppn)]²⁺ (tpy = 2,2′:6′,2″-terpyridine; pydppn = 3-(pyrid-2′-yl)-4,5,9,16-tetraaza-dibenzo[a,c]naphthacene) was synthesized and characterized to evaluate the effect of an extended planar π-system on photophysical properties and DNA interactions. This complex represents the π-expanded analog of the previously studied [Os(tpy)(pydppz)]²⁺ system. Electrochemical studies revealed a reversible Os(II)/Os(III) oxidation at +0.99 V vs. SCE and five ligand-centered reductions, generally less negative than those of the smaller pydppz analog, consistent with enhanced electron-accepting ability. In acetonitrile, the complex exhibits UV absorption bands at 328 and 473 nm and near-infrared emission at 840 nm, assigned to a long-lived ³MLCT state (τ = 110 ns, Φ = 0.02). Upon titration with calf-thymus DNA, [Os(tpy)(pydppn)]²⁺ shows a pronounced light-switch effect, hypochromism, red-shifted MLCT bands, induced circular dichroism, and an increase in DNA melting temperature (ΔT_m = 8.9 ± 0.5 °C), consistent with intercalative binding. Viscometric titrations further support intercalation, with a binding constant K_B ≈ 1.2 × 10⁶ M⁻¹. Transient absorption spectroscopy indicates that DNA binding prolongs the excited-state lifetime and modifies vibrational relaxation pathways. These results highlight how π-system extension in Os(II) complexes modulates photophysical behavior and DNA affinity, offering insights for the rational design of NIR-emitting, DNA-targeted luminescent probes and potential phototherapeutic agents. Full article

Background/Objective: Acute and chronic pain affect millions of individuals, yet there are currently no molecular imaging tools to directly assess pain-related mechanisms in the central nervous system (CNS). The voltage-gated sodium channel Na_V1.8 plays a pivotal role in neuropathic pain by increasing the excitability of nociceptive neurons following nerve injury or inflammation. In this work, we aimed to develop a novel positron emission tomography (PET) imaging probe for Na_V1.8 to facilitate noninvasive quantification of this target in the CNS and thereby advance our understanding of pain neurobiology. Methods: We selected the compound suzetrigine, a U.S. FDA-approved, highly selective non-opioid Na_V1.8 inhibitor, as the first candidate for a Na_V1.8-targeted PET tracer. The compound was first assessed using in silico docking and CNS multiparameter optimization (MPO) analysis to evaluate target binding and predicted brain penetrability. Radiolabeling was accomplished by O-methylation with [¹¹C]methyl iodide to yield [¹¹C]suzetrigine without structural modification. The tracer was then evaluated using in vitro binding assays, including autoradiography and saturation binding on rat brain tissues, to determine binding parameters (K_D, B_max), and using in vivo PET imaging in rats to assess brain uptake, time–activity curves (TACs), and tracer behavior under baseline and pretreatment conditions. Pretreatment was performed with unlabeled suzetrigine, the P-glycoprotein (P-gp) inhibitor verapamil, and the heterologous Na_V1.8 inhibitor A-803467. Results: In silico docking demonstrated favorable binding of suzetrigine to the Na_V1.8 active site, and the calculated CNS MPO score (>3.5) suggested adequate brain penetration. Radiochemical synthesis of [¹¹C]suzetrigine via O-methylation yielded a high decay-corrected radiochemical yield (19.2 ± 2.7%, n = 3), excellent purity (>98%, n = 3), and moderate molar activity (62.9 ± 51.8 MBq/nmol, n = 3). Autoradiography on rat brain tissue confirmed saturable and selective binding of [¹¹C]suzetrigine to Na_V1.8. Saturation binding assays revealed a B_max = 93 fmol/mg and a K_D = 0.1 nM, supporting the imageability of Na_V1.8 in the brain using this tracer. In vivo PET imaging in rats demonstrated rapid and sufficient brain uptake but revealed unexpected tracer behavior: signal intensity markedly increased following pretreatment with either unlabeled suzetrigine or the P-gp inhibitor verapamil, and showed a slight increase after pretreatment with the heterologous Na_V1.8 inhibitor A-803467. Detailed analysis of PET images, TACs, and normalized area-under-curve (AUC) values indicated that these atypical uptake patterns were primarily attributable to P-gp-mediated effects, although additional factors may also contribute. Conclusions: [¹¹C]Suzetrigine exhibits high affinity, good brain uptake, and selective target engagement in vitro, supporting its potential as a first-in-class Na_V1.8-PET tracer. However, in vivo performance is confounded by P-gp-mediated efflux and possibly other mechanisms that limit accurate quantification of Na_V1.8 in the living brain. These findings underscore the critical role of efflux transporters in CNS radiotracer development and highlight the need for design strategies that mitigate P-gp interaction when targeting ion channels in the brain. Future studies will include imaging under constant P-gp inhibition, arterial blood sampling for radiometabolite analysis and full kinetic modeling, and evaluation in non-human primates to assess translational feasibility. Full article

Tyrosine kinases (TKs) and cyclin-dependent kinases (CDKs) contain reactive cysteines that can be exploited by targeted covalent inhibitors. In this exploratory computational study, we asked whether selected natural-product-like (NP-like) electrophiles bearing Michael-acceptor (MA) motifs could adopt geometries consistent with covalent approaches to these cysteines, in a manner analogous to approved covalent TKIs. Using AutoDockFR with cysteine-centered grids and explicit side-chain flexibility, we performed pocket-focused, within-receptor covalent docking for EGFR, VEGFR2/KDR, PDGFRβ (via PDGFRα surrogate), BTK, CDK7, and CDK12. Reference inhibitors (osimertinib–EGFR, ibrutinib–BTK, THZ1–CDK7, and THZ531–CDK12) reproduced the expected geometries and served as internal controls. NP-like electrophiles (parthenolide, withaferin A, celastrol, and curcumin as a low-reactivity geometry probe) displayed pocket-compatible orientations in several targets, particularly EGFR and BTK, suggesting feasible pre-reaction alignment toward the reactive cysteine. Although no quantitative affinity was inferred, the consistent geometric feasibility supports their potential as structural templates for covalent-binding natural scaffolds. These results provide a qualitative, structure-based rationale for further chemoproteomic and enzymatic validation of NP-derived or hybrid compounds as potential leads in cancer therapy, expanding covalent chemical space beyond existing synthetic scaffolds. Full article

Background: Mitoxantrone (MX) is regularly used to treat several cancers. Despite its long history in the clinic, recent studies continue to unveil novel protein targets. These targets may contribute to the cytotoxic effects of the drug, as well as potential non-canonical antitumor activity. A better understanding of MX’s cellular targets is required to fully comprehend the molecular consequences of treatment and to interpret MX sensitivity in homologous recombination (HR)-deficient cancer. Methods: Here, we evaluated MX activity in HR-deficient UWB1.289 (BRCA1−) ovarian cancer cells and surveyed the binding profile of MX using TMT-labeled quantitative proteomics and chemoproteomics. Results: Mass spectrometry (MS) analysis of cellular extracts from MX-treated BRCA1−UWB1.289 cells revealed unique downregulation of pathways instrumental in maintaining genomic stability, including single-strand annealing. Moreover, the BRCA1− cells exhibited a significant upregulation of proteins involved in ribosome biogenesis and RNA processing. Additional MS analyses following affinity-purification using a biotinylated-mitoxantrone probe corroborated these findings, which showed considerable targeting of proteins involved in genome maintenance and RNA processing. Conclusions: Our results suggest that an interplay of both canonical and non-canonical MX-antitumor activity overwhelms the BRCA1− UWB1.289 cells. Furthermore, this study characterizes the target landscape of MX, providing insights into off-target effects and MX action in HR-deficient cancer. Full article

Radionuclide molecular imaging of epidermal growth factor receptor (EGFR) expression might permit the selection of patients for EGFR-targeting therapies. Designed ankyrin repeat protein (DARPin) E01 with a high affinity to the ectodomain III of the EGFR is a possible EGFR imaging probe. The goal of this study was to evaluate the potential of radiolabeled DARPin E01 for in vivo imaging of EGFR. DARPin E01 containing the (HE)₃-tag was site-specifically labeled with a residualizing ^99mTc (using ^99mTc]Tc(CO)₃). Two methods providing non-residualizing ¹²³I labels, direct electrophilic radioiodination and indirect radioiodination using [¹²³I]I-para-iodobenzoate (PIB), were tested. [^99mTc]Tc-(HE)₃-E01 and [¹²³I]I-(HE)₃-E01-PIB preserved specific binding to EGFR-expressing cells and affinity in the single-digit nanomolar range. Direct labeling with ¹²³I resulted in a substantial loss of binding. In vitro cellular processing studies showed that both [^99mTc]Tc-(HE)₃-E01 and [¹²³I]I-(HE)₃-E01-PIB had rapid binding and relatively slow internalization. Evaluation of [^99mTc]Tc-(HE)₃-E01 biodistribution in normal CD1 mice showed that its hepatic uptake was non-saturable, suggesting that this tracer does not bind to murine EGFR. A side-by-side comparison of biodistribution and tumor targeting of [^99mTc]Tc-(HE)₃-E01 and [¹²³I]I-(HE)₃-E01-PIB was performed in Nu/j mice bearing EGFR-positive A-431 and EGFR-negative Ramos human cancer xenografts. Both radiolabeled DARPins demonstrated EGFR-specific tumor uptake. However, [¹²³I]I-(HE)₃-E01-PIB had appreciably lower uptake in normal organs compared to [^99mTc]Tc-(HE)₃-E01, which provided significantly (p < 0.05) higher tumor-to-organ ratios. Gamma-camera imaging confirmed that [¹²³I]I-(HE)₃-E01-PIB demonstrated a higher imaging contrast in preclinical models than [^99mTc]Tc-(HE)₃-E01. In conclusion, DARPin (HE)₃-E01 labeled using a non-residualizing [¹²³I]I-para-iodobenzoate (PIB) label is the preferred radiotracer for in vivo imaging of EGFR expression in cancer. Full article

Nucleic acid aptamers leverage defined tertiary structures for precise molecular recognition, positioning them as transformative biomedical tools. We engineered AP1-F, a G-quadruplex (G4)-structured aptamer that selectively binds membrane-anchored nucleolin (NCL) non-permeabilizing, overcoming a key limitation of conventional probes. Microscale thermophoresis confirmed nanomolar affinity to NCL. By means of rigorous optimization, AP1-F attained a greater than ten-fold fluorescence signal ratio between malignant and normal cells in co-cultures, exceeding the extensively researched AS1411. Dual-channel flow cytometry demonstrated over 98.78% specificity at single-cell resolution within heterogeneous cell populations, owing to AP1-F’s unique membrane localization—unlike AS1411’s intracellular uptake, which elicited erroneous signals from cytoplasmic NCL. Competitive binding experiments and Laser Confocal Imaging confirmed that AP1-F specifically identifies cancer cells by binding to the NCL recognition site on the membrane. In pathological sections, AP1-F exhibited a 40.5-fold fluorescence intensity ratio between tumor and normal tissue, facilitating accurate tissue-level differentiation. Significantly, it delineated molecular subtypes by associating membrane NCL patterns with morphometric analysis: luminal-like MCF-7 displayed consistent staining in cohesive clusters, whereas basal-like MDA-MB-468 revealed sporadic NCL with irregular outlines—characteristics imperceptible to intracellular-targeted antibodies, thus offering subtype-specific diagnostic insights. This combination biochemical–morphological approach accomplished subtype differentiation with a single-step, non-permeabilized process that maintained lower cytotoxicity and tissue integrity. AP1-F enhances diagnostic accuracy by utilizing spatial confinement to eradicate intracellular interference, connecting molecular specificity to intraoperative margin evaluation or biopsy categorization. Full article

Capsaicinoids (CPCs) are regarded as a typical marker of waste oil, which has emerged as a serious food safety issue in developing countries, necessitating the development of rapid, sensitive, and specific detection methods. In this study, a novel hapten was synthesized to generate a high-affinity monoclonal antibody (mAb) targeting CPCs. Subsequently, aggregation-induced emission fluorescent microspheres (AIEFMs), known for their superior fluorescence intensity, were utilized as an enhanced probe to develop a lateral flow immunoassay (LFIA) based on mAb 8B4 for CPC detection. For comparison, a traditional gold nanoparticle (AuNP)-LFIA was also constructed using the corresponding mAb. The AIEFM-LFIA demonstrated a limit of detection (LOD) of 0.33 µg/kg for CPCs in edible oil samples, which is 4.21 times lower than the LOD of 1.39 µg/kg achieved by the AuNP-LFIA. And the assay effectively identified three additional CPCs, with LODs ranging from 0.26 to 0.99 µg/kg, while exhibiting minimal cross-reactivity with CPC analogs, indicating high specificity. The recovery rates of the AIEFM-LFIA in oil samples ranged from 75.0% to 106.0%, with coefficients of variation ≤ 8.3%, exhibiting excellent accuracy and precision. Furthermore, the results of the AIEFM-LFIA demonstrated a strong degree of correlation with liquid chromatography–tandem mass spectrometry, with a correlation coefficient (R²) of 0.978. Consequently, the developed AIEFM-LFIA shows significant promise as a rapid, sensitive, specific, and reliable method for detecting CPCs in oil samples. Full article

This study investigates the mineralogical and physical properties of serpentinite from the Monteferrato area (Tuscany, Italy) to evaluate its potential use in Tuscany architectural restoration. The research addresses the need to identify replacement materials compatible with historic stones while preserving their original features. Representative specimens from the Bagnolo quarry were analysed through physical testing and a wide range of mineralogical and geochemical techniques, including polarised light microscopy, X-ray diffraction, electron probe micro-analysis, whole-rock chemistry, and fibre quantification. The results show a mineralogical composition dominated by serpentine-group minerals and magnetite, with physical properties generally consistent across samples. Measured capillary water absorption ranges from 3.27 to 5.27 g/m²·s^0.5, open porosity from 5.25% to 8.93%, apparent densities range from 2.49 to 2.56 g/cm³, and imbibition coefficient from 2.16% to 3.71%. Comparative analysis with serpentinite from historic sources (Figline di Prato quarry, Tuscany) and from monuments (Baptistery of San Giovanni, Florence) demonstrates close compositional and textural affinities, supporting the suitability of the rock from the studied quarry for restoration purposes in Tuscany monuments. However, chrysotile concentrations up to 14,153 mg/kg, exceeding Italian regulatory thresholds, represent a critical limitation. This not only requires the implementation of strict safety measures but also raises serious concerns regarding the practical feasibility of using this stone in conservation projects. More broadly, the presence of asbestiform minerals in serpentinites highlights a significant and often underestimated health risk associated with their extraction, processing, and use. Despite its importance, detailed fibre count data are rarely published or made publicly accessible, hindering both transparent risk assessment and informed decision-making. By integrating petrographic, mineralogical, and physical–mechanical characterisation with fibre quantification, this study not only assesses the technical suitability of Monteferrato serpentinites for restoration of Tuscan monuments but also contributes to a more responsible and evidence-based approach to their use, emphasising the urgent need for transparency and health protection in conservation practices. Full article

The Southern Great Xing’an Range (SGXR), an important W–Sn polymetallic metallogenic belt in northern China, hosts multiphase magmatism and has witnessed recent discoveries of multiple tungsten–tin polymetallic deposits. The W–Sn mineralization in this area is intimately associated with Early Cretaceous highly fractionated granites. The Chamuhan deposit, a small-sized W–Mo polymetallic deposit in SGXR, is genetically linked to a concealed fine-grained porphyritic alkali feldspar granite intrusion. In this study, we present the LA-ICP-MS zircon U-Pb ages, whole-rock geochemical, and electron probe microanalysis (EPMA) mineral chemistry to constrain the petrogenesis and metallogenic implications of this granite. Zircon U–Pb dating yields a crystallization age of 141.3 ± 1.2 Ma, consistent with molybdenite Re–Os ages. The granite is characterized by elevated SiO₂ (76.9–79.1 wt%) and total alkalis (7.3–8.5 wt%), and exhibits peraluminous high-K calc-alkaline affinity (A/CNK = 1.37–1.57). Geochemical signatures reveal enrichment in large ion lithophile elements (LILEs, e.g., Rb, Th, U) coupled with depletion in high-field strength elements (HFSEs, e.g., Ba, Sr, P, Eu, Ti, Nb, Ta), and are accompanied by right-sloping REE patterns with LREE enrichment and HREE depletion. EPMA data indicate that the mica in the intrusion is primarily zinnwaldite and Li-rich phengite, whereas the plagioclase occurs as albite. The feldspar thermobarometry yields crystallization temperatures of 689–778 °C and 313 MPa–454 MPa, while the melt H₂O content and oxygen fugacity are 8.61–11.1 wt% and −22.58–−14.48, respectively. These geochemical signatures indicate that the granites are highly fractionated I-type granites with extensive fractional crystallization of various minerals like plagioclase, K-feldspar, and apatite, etc. From the Late Jurassic to the Early Cretaceous, the subduction and rollback of the Paleo-Pacific Ocean plate resulted in extensional tectonic environments in eastern China. Asthenospheric upwelling and lower crustal melting generated parental magmas, wherein progressive fractional crystallization during ascent concentrated ore-forming elements and volatiles within residual melts. This process played a key role in the formation of the Chamuhan deposit, exemplifying the metallogenic potential of highly evolved granitic systems in the SGXR. Full article

Glycosaminoglycans (GAGs) are part of the extracellular matrix (ECM) and play a major role in maintaining their physiological function. During pathological processes, the ECM is remodeled and its GAG composition changes. Hyaluronic acid (HA) is one of the GAGs that plays an important role in pathological processes such as inflammation and cancer and is therefore an interesting target for imaging. To provide iron oxide nanoparticles (IONP) that bind to hyaluronic acid (HA) as specific probes for molecular imaging, a peptide with high affinity for HA was covalently bound to the surface of commercial IONP (synomag^®-D, NH2) leading to hyaluronic acid-specific iron oxide nanoparticles (HAIONPs). Affinity measurements using a quartz crystal microbalance (QCM) showed a very high affinity of HAIONP to HA, but not to the control chondroitin sulfate (CS). HAIONPs exhibit a very high magnetic particle spectroscopy (MPS) signal amplitude, which predestines them as HA-selective tracers for magnetic particle imaging (MPI). The high relaxivity coefficient r₂ also makes HAIONP suitable for magnetic resonance imaging (MRI) applications. HAIONP therefore offers excellent prerequisites for further development as a probe for the specific quantitative imaging of the HA content of the ECM in pathological areas. Full article