Thermal-based droplet analysis enables label-free composition sensing from fundamentals to biomedical applications.

Prussian Blue composite nanozymes (PB C-NZs) have been extensively employed in various biomedical applications. However, due to the complexity of its multi-enzyme activities and structural components, designing material composition and processes, optimizing specific enzymatic properties of materials, and exploring the scientific mechanisms involved remain important challenges. Given the equal importance of electron transfer optimization and intrinsic redox properties, we propose an interfacial assembly strategy that leverages electron transfer and energy band structure, allowing for the synergistic interactions between internal and interfacial electrons of the nanocomposites (MoS2/PB) and thereby enhancing the enzyme-like activity. In the MoS2/PB system, a distinct inter-nanozyme electron transfer is operative, facilitating directional electron transport from MoS2 to PB, thereby enhancing catalytic activity. Concurrently, band modulation effects induced by the interaction between MoS2 and PB effectively enhance the reductase-like catalytic activity. Notably, the expression of multiple enzyme activities can be enriched through band regulation. The comprehensive enzymatic activity tests demonstrated that MoS2/PB exhibits enhanced multiple-enzyme activities, including catalase, peroxidase, superoxide dismutase, glutathione peroxidase, S-nitrosoglutathione reductase, and nitrite reductase. This study introduces a novel design concept for composite nanozymes based on electron transfer modulation, providing valuable insights and guidance for the development of high-performance nanozymes.

Embolization is an effective treatment modality for intermediate- and advanced-stage Hepatocellular carcinoma (HCC). Transarterial radioembolization (TARE), which combines radiotherapy with embolization, not only induces tumor necrosis by occluding blood flow with embolic agents but also exerts local radiotherapeutic effects to damage tumor cells, thereby significantly enhancing the therapeutic efficacy of embolization. Current radiolabeled microspheres used for internal irradiation therapy in HCC have limitations, such as suboptimal embolization efficacy, a tendency for non-target embolization, an inability to track embolic agents during and after surgery, and the generation of reactive oxygen species (ROS) during radiotherapy, which can damage normal tissues. To address these issues, visualizable cationic quaternary ammonium salt-based drug-eluting microspheres capable of loading 131I and the radioprotective agent amifostine were developed. The microspheres exhibit good embolic properties and can be visualized over an extended period using CT and DSA. The microspheres, carrying a positive charge, are capable of loading amifostine via ion exchange. After loading amifostine, these microspheres can not only provide local radiotherapy within the tumor but also continuously release amifostine locally to neutralize ROS in normal liver tissue. This approach not only enhances the utilization of amifostine in vivo but also protects the liver without compromising the efficacy of TARE thereby further improving the precision of radiotherapy.

Organ vitrification, a cryopreservation technique achieved by vascular perfusion of cryoprotective agents (CPAs) and rapid cooling to a stable glass-like state, enables long-term organ preservation in cryogenic state. However, rewarming vitrified organs to a transplantable state remains a major challenge, as it requires rapid and uniform heating to prevent ice recrystallization and mechanical cracking. Nanowarming, which exploits the heat-generating properties of iron oxide nanoparticles (IONPs) under an alternating magnetic field (AMF), has been shown to enable successful recovery of vitrified organs through vascular perfusion and AMF-induced homogeneous warming. Yet, the potential use of clinically approved IONPs, such as Ferumoxytol, in nanowarming has not been investigated. Here, we report pivotal studies on the vitrification and nanowarming of rat kidneys using Ferumoxytol. Our findings demonstrate that Ferumoxytol remains highly stable in CPAs, enables a similar to 10-fold faster warming rate (similar to 79.9 degrees C/min) than the cooling rate (similar to 8.0 degrees C/min), and produces uniform warming kinetics across the cortex, medulla, and hilum of rat kidneys. Importantly, vitrified kidneys recovered by Ferumoxytol-based nanowarming exhibited comparable viability to both fresh controls and static cold stored kidneys, as assessed by renal pathology and vascular endothelium staining. Given its established clinical use as an iron supplement and MRI contrast agent, Ferumoxytol may serve as a readily translatable nanowarming agent, potentially accelerating the clinical adoption of organ vitrification and nanowarming.

Magnetic micro-and nano-architectures (MMNAs) have emerged as powerful tools in analytical chemistry due to their unique physicochemical properties, mainly responsible for the separation, enrichment, and signal detection of target analytes. This review provides a comprehensive overview of the properites, synthesis, design, and multifunctional applications of these materials. Firstly, we summarized the core magnetic properties and the synthesis strategies developed for their functionality. Then, we delved into their various cutting-edge applications, emphasizing their roles as separation and enrichment tools, signal sources in magnetic sensing, signal enhancers in biosensors, and actuators for droplet manipulation. Finally, we discuss the current challenges and future perspectives. MMNAs will undoubtedly be an important driving force for the development of next-generation analytical platforms.

Iron-based magnetic nanomaterials are increasingly utilized as therapeutic agents because of their unique physicochemical properties. Upon administration, they are predominantly phagocytosed by the mononuclear phagocytic system, where they undergo lysosomal digestion and contribute to cellular iron metabolism, thereby influencing systemic iron homeostasis. Macrophages are the primary targets of iron-based magnetic nanomaterials and they play a crucial role in innate immunity. Functional plasticity and phenotypic alterations are associated with cellular and systemic iron regulation. This review provides a comprehensive discussion of the recent advancements in understanding of the metabolic fate of iron-based nanomaterials within monocytes/macrophages and their impact on macrophage function. The review focuses on investigating the roles of iron-based magnetic nanomaterials in mimicking enzyme-like activities, modulating iron metabolism, influencing cellular signaling pathways, and affecting mitochondrial energy metabolism and magnetic field responsiveness. Furthermore, this review addresses the current strategies and challenges in utilizing iron-based nanomaterials for macrophage-targeted diagnosis and therapy. This review aims to elucidate the complex processes and key factors through which iron-based magnetic nanomaterials mediate macrophage modulation, thereby providing a scientific rationale for the future design of macrophage-targeted applications.

Osteoarthritis (OA) is a degenerative joint disease characterized by obscure etiology and unsatisfactory therapeutic outcomes, making the development of new efficient therapies urgent. Superfluous reactive oxygen species (ROS) have historically been considered one of the crucial factors inducing the pathological progression of OA. Ultrasmall Prussian blue nanoparticles (USPBNPs), approximately sub-5 nm in size, are developed by regulating the configuration of polyvinylpyrrolidone chains. USPBNPs display an excellent ROS eliminating capacity and catalase-like activity, capable of decomposing hydrogen peroxide (H2O2) into O2. The anti-inflammatory mechanism of USPBNPs can be attributed to repolarizing macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype by decreasing the ROS levels accompanied by O2 improvement. Additionally, USPBNPs exhibit an exciting therapeutic efficiency against OA, comparable to that of hydrocortisone in vivo. This study not only develops a new therapeutic agent for OA but also offers an estimable insight into the application of the nanozyme.

Iron oxide nanoparticles (IONPs) demonstrate substantial translational potential in precision medicine, leveraging their favourable biocompatibility and distinctive magnetic properties. This comprehensive review systematically analyses their established clinical applications including magnetic resonance imaging (MRI) contrast enhancement, oncological interventions, and iron deficiency therapies. It further examines the critical design parameters governing the performance, safety, and metabolic fate of IONPs from a clinical-translational perspective. It addresses pivotal challenges in their clinical application and translation, including synthetic reproducibility, scalable manufacturing, and long-term biosafety, while also reviewing recent promising advances aimed at overcoming these hurdles. Furthermore, the translational potential of emerging preclinical innovations, including magnetic particle imaging (MPI), stem cell tracking modalities, and novel oral iron supplementation approaches, was critically evaluated. When integrated with multimodal imaging platforms and personalized therapeutic regimens, these advancements would pave the way for IONPs to become transformative agents in next-generation precision medicine.

Given that reactive oxygen species (ROS) accumulation and inflammatory microenvironments are key issues hindering wound repair, nanozyme-functionalized hydrogels have been widely used in different types of wound healing modes to regulate ROS. Since wound healing is a long-term process, the long-term effectiveness or even enhancement of enzyme-like activities of hydrogels is critical. Based on the electron transfer catalytic mechanism and enzyme-like activity enhancement effect of Prussian blue nanozymes (PBNZs), this study used classic hydrogel materials as carriers and PBNZs as functionalized nanozymes to construct a wound dressing with enhanced enzyme-like activity. In the system, the effect of self-enhanced enzyme activity as a wound dressing and the good promotion effect on the healing of skin defect models were successfully verified. Moreover, PBNZs can be stably fixed in the hydrogel system and will not be released during the application process, which is a necessary condition for achieving enzyme-like activity self-enhancement. It is precisely due to the self-enhanced effect of its enzyme-like activity that PBNZs can express excellent ROS regulation ability in the effective contact area. This article explores the intrinsic properties of PBNZs-based hydrogels for wound healing, focusing on their catalytic mechanisms. The developed PBNZs-functionalized hydrogel shows significant potential as an advanced dressing to accelerate wound healing. Notably, the self-enhanced wound dressing with enzyme-like activity proposed in this study offers valuable insights for material design in this field.

Radiation therapy (RT) is one of the most effective and widely used treatment methods for glioblastoma multiforme (GBM). However, its efficacy is often compromised by the inherent radioresistance of tumor cells, while the restrictive nature of the blood-brain barrier (BBB) specifically impedes the delivery of radiosensitizer. Thus, we constructed and characterized polyethylene glycol (PEG)-functionalized silver-gold core-shell nanoparticles (PSGNPs) targeting both BBB (TfRA4) and GBM (DNA1) (TDSGNPs). Afterwards, studies conducted both in vitro and in vivo were employed to assess the BBB penetration capabilities, abilities of GBM targeting and radiosensitization effect. Transmission electron microscope images of PSGNPs showed a core-shell structure, and the results of ultraviolet-visible absorption spectroscopy and dynamic light scattering displayed that TDSGNPs were successfully constructed with excellent dispersion properties. TDSGNPs could be specifically taken up by U87MG cells and the uptake peaked at 24 h. TDSGNPs combined with RT obviously increased the apoptosis proportion of the cells. It was shown by the in vitro and in vivo investigations that TDSGNPs could target U87MG cells after crossing the BBB, and further study revealed that TDSGNPs showed an uptake peak in the tumor sites after 3 h intravenous injection. The radiosensitization of TDSGNPs was better than that of the nanoparticles modified with single aptamers and the median survival of tumor-bearing mice was greatly extended. This study demonstrated that TDSGNPs could penetrate BBB to target GBM, functioning as a promising radiosensitizer for the targeted therapy of GBM.

Abstract Iron-based nanozymes mimic key enzymatic activities while offering the design flexibility and stability of nanomaterials. Advances in single-atom engineering, defect modulation, biomimetic synthesis, and multienzyme synergy have expanded their peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-, and oxidase (OXD)-like functions, enabling broad biomedical applications in cancer therapy, infection control, neuroprotection, and diagnostics. However, key druggability challenges, such as synthesis reproducibility, structural and functional stability, controllable pharmacokinetics, and immunological safety, continue to hinder clinical translation. This Review provides a comprehensive and structured analysis of iron-based nanozymes from the perspective of druggability optimization. It highlights recent progress in catalytic mechanism elucidation, structure–activity relationship engineering, responsive behavior tuning, and therapeutic performance evaluation. The emphasis is placed on the integration of artificial intelligence (AI) for rational design, the development of standardized characterization and quality control protocols, and the implementation of scalable, good manufacturing practice (GMP)-compliant production pathways. By aligning catalytic innovation with translational requirements, iron-based nanozymes are advancing toward next-generation theranostic platforms capable of microenvironmental remodeling and intelligent treatment integration.

Noninvasive therapies such as photodynamic therapy (PDT) and chemodynamic therapy (CDT), which rely on reactive oxygen species (ROS), are gaining attention for their low toxicity. However, single-modal treatments have individual limitations that restrict the therapeutic efficacy. Fe(III) can coordinate with the hydrophilic regions of indocyanine green (ICG) molecules to form the ICG/Fe(III) complex, making it a promising dual-modal agent for combined PDT and CDT. However, coordination with Fe(III) leads to the aggregation quenching of ICG, hindering its application in dual-modal therapy. We innovatively utilize oxygen nanobubbles, prepared solely from water and oxygen, to significantly reverse the aggregation-induced quenching of the ICG/Fe(III) complex, thereby enhancing its stability in aqueous environments. In this system, Fe(III) assembles at the nanobubble interface, coordinating with ICG's hydrophilic regions to form the ICG/Fe(III)-NBs. The oxygen nanobubbles boost PDT efficiency by improving the ICG/Fe(III) complex stability and oxygen content, while Fe(III) achieves CDT by generating hydroxyl radicals (•OH) through the Fenton reaction. This dual-modality treatment significantly disrupts the tumor's redox balance, induces ferroptosis, and demonstrates strong antitumor efficacy, reducing tumor volume to 34% of its initial size in mice. The strategy offers a promising and clinically viable approach to cancer treatment.

As a typical multi-enzymic nanozyme, Prussian blue nanozymes (PBNZs) mimic the catalytic functions of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) enzymes in a pH-dependent manner. Due to their capacity to modulate reactive oxygen species (ROS), PBNZs are considered a promising tool for immune modulation, particularly in the directional regulation of macrophage polarization. However, the biological dynamics of pH-dependent multienzyme activity in cells remain poorly understood. Here, we demonstrate that the intracellular localization of PBNZs is a critical factor in their regulation of ROS and macrophage polarization. Smaller-sized PBNZs (3 nm) efficiently bypass acidic lysosomal environments (pH 4.6) and accumulate in the cytosol (pH 7.4) where they exhibit reduced POD-mimic activity and enhanced CAT- and SOD-mimic functions. Conversely, larger-sized PBNZs (60 nm and 170 nm) predominantly remained in acidic lysosomes (pH 4.6), exhibiting stronger POD-mimic activity but minimal CAT-mimic function. Additionally, we identify hypoxia-inducible factor 1-alpha (HIF-1a) as a potential mediator that senses alterations in intracellular oxygen(O2) levels induced by PBNZs, thus modulating the transcription of genes involved in macrophage polarization. Moreover, oral administration with 3 nm PBNZs effectively mitigated dextran sodium sulfate (DSS)-induced acute colitis in mice, owing to their great capacity to modulate macrophage function. Our study provides insights into the complex behavior of multi-enzymatic PBNZs within the intracellular milieu, reveals their protective effect in treating colitis, and offers a foundational rationale for the tailored design of multi-enzymic nanozymes with specific macrophage modulatory properties for prophylactic applications.

Prussian blue nanozymes (PBNZ) have emerged as promising biomedical agents due to their enzyme-mimetic activities, photothermal properties, and magnetic resonance imaging (MRI) contrast capabilities. However, their practical utility is limited by aggregation tendencies arising from high surface energy. Here, we present a strategy employing spherical polyelectrolyte brushes (SPB) as nanoreactors to synthesize satellite-structured SPB@PBNPs with well-defined dimensions (15-19 nm) and low crystallinity. Through systematic optimization of the mFe3+/mSPB ratio (1, 4) and acidic co-precipitation conditions, uniform anchoring of PBNPs on SPB surfaces was achieved. Comprehensive characterization, including TEM, FTIR, XRD, DLS, and UV-vis, confirmed the structural integrity and monodispersity of the hybrid system. Analysis of crystal growth indicated a nonclassical crystallization pathway, driven by Donnan-like effect mediated Fe3+ confinement at SPB interfaces, which facilitated heterogeneous nucleation and oriented nanoparticle attachment. The three-dimensional brush architecture endowed SPB@PBNPs with remarkable environmental stability across a broad pH range (3.0-7.0) and temperature range (4-60 °C). Enzymatic assays demonstrated enhanced catalytic performance compared to conventional PBNPs (74 nm), exhibiting 3.7-fold enhanced peroxidase-like activity and 3-fold elevated catalase-like activity, attributed to optimized electronic structures and increased active site accessibility due to reduced crystallinity. Furthermore, SPB@PBNPs displayed exceptional photothermal conversion efficiency (60.4 %), MRI contrast capability (r1 = 0.8406 mM-1·s-1), and good biocompatibility. This work elucidates the crystallization dynamics and catalytic enhancement mechanisms of brush-stabilized nanozymes, offering a robust framework for designing multifunctional nanozymes with synergistic catalytic efficiency and environmental resilience.

Due to the complexity of their multiple structures, the catalytic mechanism of Prussian blue composite nanozymes (PB C-NZs) remain to be fully elucidated. Meanwhile, there is currently no relatively clear design concept for the construction of PB C-NZs. Given that PBNZs have an electron transfer catalytic mechanism and intrinsic properties of redox, this work proposes a novel design concept based on electron transfer and energy band difference to improve catalytic activity and oxidation performance. In short, a PB C-NZs with region growing is developed by in situ doping with MoO3 to increase the active sites and adjust the band position to regulate redox ability. The energy band overlap region of MoO3 and PB can be used to reduce the band gap for improving the electron transfer efficiency. And its oxidative enzyme-like performance results show that compounds with higher valence bands can be used to improve the oxidation performance. This confirms that the oxidation enzyme-like performance of PB C-NZs are enhanced by energy band differences. The design concept clarifies the factors and electron transfer mechanism of the MoO3/PB nanozyme to enhance enzyme activity and proposes a novel concept for the design of subsequent redox nanozymes.

Spider silk plays a pivotal role in the diverse physiological activities of spiders, with its protein components exhibiting remarkable mechanical properties and biocompatibility. Spider silk proteins exhibit a high degree of repetitiveness, primarily constructed through the recurring arrangement of amino acid motifs, including (A)n, (GA)n, (GGX)n, and (GPGXX)n sequences. These repetitive sequences endow spider silk with different material properties. Recombinant spider silk proteins are produced through heterologous expression systems, and then spun into nanofibers using artificial spinning technology. These fibers have broad potential applications in the biomedical field, such as tissue engineering scaffolds, drug delivery carriers, sutures, and other biomaterials. However, enhancing the yield and performance of recombinant spider silk proteins, while facilitating large-scale production, continues to pose a significant challenge in the current landscape.

Radiotherapy is an important part of standard treatment for triple-negative breast cancer (TNBC); however, radioresistance significantly limits therapeutic outcomes. In this study, we developed a novel radiosensitizer based on aptamer-modified silver nanoclusters, NC-T5-5TR1, to potentiate radiotherapy efficacy against TNBC. NC-T5-5TR1 enabled real-time tumor imaging and accurate localization via their intrinsic fluorescence and targeting capability. When combined with ionizing radiation (IR), NC-T5-5TR1 significantly enhanced radiosensitization in vitro, as evidenced by decreased proliferation, increased apoptosis and higher reactive oxygen species (ROS) levels, and also markedly inhibited tumor growth in vivo. Transcriptomic analysis indicated that the IL-6/JAK2/STAT3 signaling pathway was downregulated under NC-T5-5TR1 + IR treatment, which was subsequently validated in vitro and in vivo. Rescue experiments confirmed that IL-6 overexpression reversed NC-T5-5TR1 combined with IR-induced JAK2/STAT3 inhibition and its downstream effects on proliferation, apoptosis, and ROS accumulation. Collectively, our findings demonstrated that NC-T5-5TR1 enhanced the radiosensitivity of TNBC cells, and this effect was associated with the modulation of the IL-6/JAK2/STAT3 axis, offering a promising strategy for improving the therapeutic efficacy of radiotherapy in TNBC.

The Ti6Al4V (TC4) alloy, a prevalent biomedical material in orthopedics, still faces limitation of the insufficient osseointegration. To improve the bioactivity of TC4, introducing the electric environment onto the TC4 surface may be an effective way in the view of the necessity of endogenous electric microenvironment in bone regeneration. Herein, a Volta potential pattern was engendered on the TC4 surface via parallel laser patterning, so as to promote the osteogenic differentiation of cells. A 15 W laser successfully transformed the original alpha + 8 dual phase towards radially distributed lath-like martensite phase in the laser treated region. The atomic lattice distortion between the heterogeneous microstructures of the laser treated and untreated regions leads to a significant Volta potential fluctuation on the TC4 surface. The Volta potential pattern as well as the laser-engraved microgrooves respectively induced mutually orthogonal cell alignments. The hBMSCs osteogenic differentiation was significantly enhanced on the laser treated TC4 surfaces in comparison to the surface without the laser treatment. Moreover, a drastic Volta potential gradient on the TC4 surface (treated with 15 W power and 400 mu m interval) resulted in the most pronounced osteogenic differentiation tendency compared to other groups. Modulating the electric environment on the TC4 surface by manipulating the phase transformation may provide an effective way in evoking favorable cell response of bone regeneration, thereby improving the bioactivity of TC4 implant.