Diabetic wounds are a major clinical challenge, driven by hyperglycemia, oxidative stress, persistent inflammation, and bacterial infection. Conventional dressings offer limited benefit, creating demand for advanced therapeutic strategies. This review analyzes hydrogel-based wound dressings and flexible electronic devices. Hydrogels are categorized by angiogenesis promotion, antioxidant activity, anti-inflammatory regulation, antibacterial action, and electrical conductivity. Flexible electronics are examined for adaptability, sensitivity, and real-time monitoring potential. Hydrogels maintain moist environments, support tissue regeneration, and deliver multifunctional bioactivity. Growth factor-loaded and electroactive hydrogels promote angiogenesis. Reactive oxygen species (ROS)-responsive systems restore redox balance. Anti-inflammatory and antibacterial hydrogels regulate macrophages and reduce infection risk. Conductive hydrogels accelerate healing through electrical stimulation. Flexible electronics provide continuous monitoring, intelligent feedback, and remote management, enhancing treatment precision. Their integration with hydrogels represents a paradigm shift from passive dressings to active diagnostic and therapeutic systems. Challenges remain in material design, interfacial stability, and long-term biocompatibility. These issues guide future innovation and clinical translation, offering a foundation for smart diabetic wound management.

Face masks serve as public and personal health protection against microorganism infection during COIVD-19 pandemic. Thermoelectric materials demonstrated their capacity for reactive oxygen species (ROS) generation and antibacterial application potential. However, owing to their low Seebeck coefficient, these binary metallic thermoelectric materials typically exhibited poor catalytic performance. In this study, structurally engineered copper-doped bismuth telluride (CBT) nanorods were fabricated with improved Seebeck coefficient and decreased thermal conductivity. Under the stimulation of a temperature difference, CBT can generate superoxide (center dot O-2(-)) and hydrogen peroxide (H2O2) to eliminate pathogenic bacteria. In addition, CBT was incorporated into poly-epsilon-caprolactone (PCL) and polyethylene glycol (PEG) fiber fabric to create a biocompatible antibacterial face mask. Due to the temperature difference between the human body and the environment during respiration, the as-prepared thermocatalytic mask exhibited a potent bactericidal effect with a 2 log(10) reduction of bacterial cell counts. To demonstrate the practical antibacterial efficacy of the thermocatalytic mask, an animal breathing model was conducted in mice and demonstrated its antibacterial activity. This work introduces a self-activated thermoelectric material platform for next-generation antimicrobial face masks, offering a promising route toward advanced personal protective equipment.

mRNA vaccines hold remarkable promise for cancer immunotherapy, yet current nanoparticle systems face challenges in efficacy, dendritic cell (DC) targeting, and safety. Herein, we report a nanoplatform, Manganese‐Coordinated Polyvalent Aptameric System (COMPASS), enabling targeted co‐delivery of mRNA and Mn 2 + to lymph node dendritic cells (DC) to boost potent antitumor immunity. The COMPASS employed rolling circle amplification to generate single‐stranded DNA scaffolds with multivalent DC‐targeting aptamers and polyT domains, enabling stable mRNA hybridization via A‐T pairing. Various metal ions were screened, and Mn 2 + was found to enhance mRNA endosomal escape and activate the STING pathway in DCs, promoting their maturation and antigen presentation. Controlled nanoparticle size (∼200 nm) and aptamer‐mediated DC targeting markedly enhanced lymphatic accumulation. In vivo evaluations revealed that COMPASS achieved potent prophylactic and therapeutic antitumor efficacy comparable to commercial LNPs (e.g., SM‐102), while exhibiting significantly enhanced safety profiles. Importantly, lyophilized COMPASS formulations retained their structural integrity and bioactivity for at least three months at room temperature. Overall, COMPASS represents a promising next‐generation nanoplatform with significant translational potential for safe and effective cancer immunotherapy.

The pursuit of high-performance myrosinase (MYR) systems for efficient production of bioactive isothiocyanates (ITCs) requires advanced enzymatic activity assays. Herein, we developed two dipyrromethene boron difluoride (BODIPY)-based fluorogenic probes for rapid and reliable monitoring of MYR activity. Upon hydrolysis by MYR, the probe BDP-GSL2 undergoes a specific cascade reaction involving glucosinolate (GSL) cleavage, Lossen rearrangement, and intermolecular cyclization, leading to a 110-fold fluorescence enhancement within 10 min at 37 °C or within 90 s at 50 °C. By BDP-GSL2, we demonstrated that Rmyr exhibited the highest catalytic efficiency among all tested microbial MYRs, both in vitro and in vivo. Furthermore, we established a high-throughput screening (HTS)-compatible, fluorescence-based method for rapid profiling of Pichia pastoris libraries expressing recombinant Rmyr. The ranking of top-performing clones from the HTS-compatible approach correlated well with results from glucose-based assays, validating the reliability of our method for identifying high-expressing clones.

Cardiovascular diseases remain a leading cause of mortality due to passive and delayed drug interventions. This study introduces an intelligent blood pressure management system (BPMS) for real-time monitoring and adaptive intervention through a closed-loop framework integrating sensors, control circuits, and microneedle electrodes. A hierarchical microneedle architecture, featuring gold nanoparticle (Au NP) electrocatalysts and copper-nitrogen-doped carbon nanoribbon (Cu-NC NB) nanozymes, selectively catalyzes the in situ generation of nitric oxide (NO) for vasodilation. To enhance NO delivery, an electroosmotic flow (EOF) mechanism extends the diffusion range up to 4 millimeters through a porous microneedle (PMN) array, enabling effective vascular penetration. In vivo studies in rabbits and pigs confirm that BPMS dynamically regulates NO release in response to fluctuating blood pressure, achieving real-time hemodynamic control. This work pioneers a closed-loop strategy for continuous blood pressure monitoring and on-demand vasodilation, offering a transformative approach to the intelligent management of cardiovascular diseases.

Albumin-based drug delivery system, exemplified by FDA-approved treatments like Abraxane, have demonstrated significant potential in cancer therapy. However, albumin carriers still suffer from poor tumor-targeting capability, leading to low efficacy and systemic side effects on healthy cells in applications. Here, we report a general method for modification of albumin drugs by aptamer coating shell that are hydrophobically inserted into the albumin surface, for constructing albumin drugs-cored spherical nucleic acid (adSNA). This adSNA platform allows for the versatile loading of various therapeutic agents, including chemotherapy drugs, polyphenols, cuproptosis inducers, and near-infrared (NIR) photosensitizers, enabling targeted tumor delivery. Compared with covalent method, the hydrophobic insertion method has been proven to be of greater simplicity, higher aptamer-grafting efficiency, superior tumor-targeting capabilities, and comparable stability under physiological conditions. In a proof-of-concept study, we delivered NIR-II photothermal agents and heat shock protein inhibitors for tumor-specific mild photothermal therapy. Compared to traditional photothermal therapy (PTT), this approach utilizes NIR-II PTT agents to achieve greater tissue penetration while downregulating heat shock proteins in tumor cells, resulting in precise thermal ablation at lower temperatures. In addition, the adSNAs are straightforward to synthesize and scalable for large-scale production, offering significant potential to advance the development of clinical targeted drugs.

The prevalent and serious antimicrobial resistance in Pseudomonas aeruginosa (PA) infections has emerged as a critical public health challenge worldwide. Pyocyanin (PYO), an important virulence component produced by PA, is considered as an ideal indicator for identifying infections linked to this pathogen. This study evaluated ten metal-organic frameworks (MOFs) as signal amplifiers for the sensitive detection of PYO. The findings reveal that electrodes modified with Cu-MOFs exhibited a notable enhancement in current for PYO reduction. Particularly, Cu-1,3,5-benzene tricarboxylic acid (Cu-BTC) demonstrated superior enhancement for PYO reduction, primarily due to its smaller particle size and larger availability of active copper sites. Building on these findings, an innovative wearable device using Cu-BTC was developed to facilitate the wireless electrochemical evaluation of PYO in wounds artificially produced in Sprague-Dawley rat models. The findings indicate that this biocompatible device not only possesses exceptional sensitivity for detecting PYO with a limit of detection (LOD) of 93.5 pM with remarkable stability and selectivity but also shows antimicrobial properties that aid in the wound healing process.

Ag2S quantum dots (QDs) show superior optical properties in the NIR-II region and display significant clinical potential with favorable biocompatibility. However, inherent defects of low targeting and poor solubility necessitate practical modification methods to achieve the theranostics of Ag2S QDs. Herein, we used rolling circle amplification (RCA) techniques to obtain long single-stranded DNA containing the PD-L1 aptamer and C-rich DNA palindromic sequence. The C-rich DNA palindromic sequences can specifically chelate Ag2+ and thus serve as a template to result in biomimetic mineralization and formation of pApt-Ag2S QDs. These QDs enable specific targeting and illuminate hot tumors with high PD-L1 expression effectively, serving as excellent molecular targeted probes. In addition, due to the high NIR-II absorption of Ag2S QDs, pApt-Ag2S QDs exhibit remarkable photothermal properties. And besides, polyvalent PD-L1 aptamers can recognize PD-L1 protein and effectively block the inhibitory signal of PD-L1 on T cells, enabling efficient theranostics through the synergistic effect of photothermal therapy and immune checkpoint blocking therapy. Summary, we enhance the biological stability and antibleaching ability of Ag2S QDs using long single-stranded DNA as a template, thereby establishing a theranostic platform that specifically targets PD-L1 high-expressing inflamed tumors and demonstrates excellent performance both in vitro and in vivo.

This review discusses the structures and engineering strategies of nanocatalysts, highlighting their underlying mechanisms and applications in cancer immunotherapy.

Expanding the family of fluorescent metal clusters beyond gold, silver, and copper has always been an issue for researchers to solve. In this study, a novel type of cysteine-capped nickel nanoclusters (Cys-Ni NCs) with bright turquoise emission was developed. The as-synthesized Ni NCs showed aggregation-induced emission enhancement (AIEE) properties across Cd2+ and various polar organic solvents. Concurrently, solvents with different viscosities were used to explore the principle of solvent-induced AIEE of Cys-Ni NCs, revealing a positive correlation between fluorescence intensity and solution viscosity. In addition, the concentration of Cd2+ that induced the AIEE effect was reduced by nearly two orders of magnitude in highly viscous solvents, indicating the possibility of Cys-Ni NCs as a promising nanomaterial platform for Cd2+ sensing analysis. Moreover, we propose a novel fluorescent sensing method for rapid detection of Cu2+ based on the carboxyl group of Cys-Ni NCs coupling with Cu2+. Further, validation of Cu2+ detecting methodologies in environmental water samples with the accuracy up to 93.94% underscores their potential as robust and efficient sensing platforms. This study expands the repertoire of fluorescent metal nanoclusters for highly sensitive and selective sensing of hazardous ions and paves the way for further exploration and wide applications in Cu2+ detection in biological and medicine fields.

Metabolic communication between intracellular metabolism and extracellular microenvironment is responsible for celluar metabolism balance and cell survival, Tumor cells adaptively regulate metabolic communication to promote hyperproliferation and immunosuppression. Herein, nanotandem-rockets (hyaluronic acid modified Mg5(CO3)4(OH)2 (H-MCH)) are developed for stepwisely disrupting metabolic communication to activate antitumor immunity. Benefiting from the nanotandem-rocket structure, H-MCH nanoplates successively disrupt the extracellular metabolite transport and intracellular carbohydrate metabolism. Theoretical simulation together with metabolomic analysis discloses the underlying mechanism of H-MCH nanotandem-rockets. The extra-/intra-celluar interruption of metabolic communication provides H-MCH nanotandem-rockets with high efficiency in tumor eradication. Moreover, the interference of metabolic communication reverses immunosuppression to facilitate the intratumoral infiltration of immune cells. With H-MCH nanotandem-rockets as an in situ vaccine, systemic antitumor immunity and immune memory effect are fabricated to eliminate tumor metastasis and recurrence. Different from traditional metabolic poisons (e.g., arsenic or cyanide), the structure of nanotandem-rockets endows chemical messengers with selective regulation to tumor metabolic communication, but with minimal influence to normal tissues. The nanotandem-rockets provide a powerful paltform to augment the regulating actitiy of chemical messengers in metabolic communication, We expect our discovery of disrupting tumor metabolic communication with chemical messengers will be a powerful strategy for tumor therapy with vast practical applications.

Immune checkpoint blockade (ICB) therapy, while achieving tremendous clinical successes, still suffers from a low objective response rate in clinical cancer treatment. As a proof-of-concept study, we propose a new immune checkpoint degradation (ICD) therapy relying on lysosome-targeting chimera (LYTAC) to deplete immune checkpoint programmed death ligand-1 (PD-L1) on the tumor cell surface. Our designed chimeric aptamer on one side targets lysosome-trafficking receptor, and on the other side allows biorthogonal covalent-conjugation-reinforced specific binding of PD-L1. This covalent LYTAC is able to hijack PD-L1 for lysosomal degradation with greatly improved efficiency over its noncovalent counterpart in complex in vivo environment. Beyond abolishing the PD-1/PD-L1 axis associated immune resistance, we demonstrate for the first time that LYTAC-triggered PD-L1 degradation could directly cause immunogenic apoptosis of tumor cells to elicit tumor-specific immune responses, offering unparalleled advantages over ICB antibody therapy. Remarkably, ICD therapy with covalent LYTAC achieves comparable or higher antitumor efficacy while causing significantly less inflammatory injury compared to antibody-based ICB therapy. Moreover, covalent LYTAC can serve as a general platform for specifically degrading other membrane-associated proteins, making it a promising tool for future applications. Our work presents a novel molecular tool for effective LYTAC in complex environments, offering valuable insights in pushing DNA-based LYTAC drugs toward in vivo and clinical applications.

The COVID-19 pandemic, which originated in Hubei, China, in December 2019, has had a profound impact on global public health. With the elucidation of the SARS-CoV-2 virus structure, genome type, and routes of infection, a variety of diagnostic methods have been developed for COVID-19 detection and surveillance. Although the pandemic has been declared over, we are still significantly affected by it in our daily lives in the post-pandemic era. Among the various diagnostic methods, nanomaterials, especially metallic nanomaterials, have shown great potential in the field of bioanalysis due to their unique physical and chemical properties. This review highlights the important role of metallic nanosensors in achieving accurate and efficient detection of COVID-19 during the pandemic outbreak and spread. The sensing mechanisms of each diagnostic device capable of analyzing a range of targets, including viral nucleic acids and various proteins, are described. Since SARS-CoV-2 is constantly mutating, strategies for dealing with new variants are also suggested. In addition, we discuss the analytical tools needed to detect SARS-CoV-2 variants in the current post-pandemic era, with a focus on achieving rapid and accurate detection. Finally, we address the challenges and future directions of metallic nanomaterial-based COVID-19 detection, which may inspire researchers to develop advanced biosensors for COVID-19 monitoring and rapid response to other virus-induced pandemics based on our current achievements.

Catalytic nanomedicine can in situ catalytically generate bactericidal species under external stimuli to defend against bacterial infections. However, bacterial biofilms seriously impede the catalytic efficacy of traditional nanocatalysts. In this work, MoSe2 nanoflowers (NFs) as piezoelectric nanozymes were constructed for dual-driven catalytic eradication of multi-drug-resistant bacterial biofilms. In the biofilm microenvironment, the piezoelectricity of MoSe2 NFs was cascaded with their enzyme-mimic activity, including glutathione oxidase-mimic and peroxidase-mimic activity. As a result, the oxidative stress in the biofilms was sharply elevated under ultrasound irradiation, achieving a 4.0 log10 reduction of bacterial cells. The in vivo studies reveal that the MoSe2 NFs efficiently relieve the methicillin-resistant Staphylococcus aureus bacterial burden in mice under the control of ultrasound at a low power density. Moreover, because of the surface coating of antioxidant poly(ethyleneimine), the dual-driven catalysis of MoSe2 NFs was retarded in normal tissues to minimize the off-target damage and favor the wound healing process. Therefore, the cascade of piezoelectricity and enzyme-mimic activity in MoSe2 NFs reveals a dual-driven strategy for improving the performance of catalytic nanomaterials in the eradication of bacterial biofilms.

Severe systemic inflammation following myocardial infarction (MI) is a major cause of patient mortality. MI-induced inflammation can trigger the production of free radicals, which in turn ultimately leads to increased inflammation in cardiac lesions (i.e., inflammation-free radicals cycle), resulting in heart failure and patient death. However, currently available anti-inflammatory drugs have limited efficacy due to their weak anti-inflammatory effect and poor accumulation at the cardiac site. Herein, a novel Fe-Cur@TA nanozyme is developed for targeted therapy of MI, which is generated by coordinating Fe3+ and anti-inflammatory drug curcumin (Cur) with further modification of tannic acid (TA). Such Fe-Cur@TA nanozyme exhibits excellent free radicals scavenging and anti-inflammatory properties by reducing immune cell infiltration, promoting macrophage polarization toward the M2-like phenotype, suppressing inflammatory cytokine secretion, and blocking the inflammatory free radicals cycle. Furthermore, due to the high affinity of TA for cardiac tissue, Fe-Cur@TA shows an almost tenfold greater in cardiac retention and uptake than Fe-Cur. In mouse and preclinical beagle dog MI models, Fe-Cur@TA nanozyme preserves cardiac function and reduces scar size, suggesting promising potential for clinical translation in cardiovascular disease.

The extensive usage of antibiotics causes the rapid evolution of drug-resistant bacteria, which seriously threaten human health. Thus, efficient strategies for treating drug-resistant bacterial infections are urgently needed. Herein, MoS2-Cu2WS4 nanosheets (MS-CWS NSs) are prepared as a near-infrared (NIR) light responsive nanozyme to effectively combat methicillin-resistant Staphylococcus aureus (MRSA) infections by catalytic/photothermal effects. By integrating oxidase (OXD)- and peroxidase (POD)-mimic catalytic activity, MS-CWS NSs have the ability to inactivate MRSA without the addition of H2O2. Moreover, the reactive oxygen species (ROS) produced from MS-CWS NSs are further enhanced by NIR light irradiation, which remarkably causes the death of MRSA. MS-CWS NSs show 4.4 log (99.996%) bacterial inactivation efficiency of MRSA in vitro under NIR light irradiation (0.8 W cm-2, 5 min). In an MRSA infected wound mouse model, MS-CWS NSs inactivate the MRSA by more than 5.2 log (>99.999%) and effectively promote wound healing. This work provides an NIR-responsive 2D nanozyme for efficient treatment of MRSA infections.

Catalytic nanomedicine, especially artificial enzymes, exhibit obvious merits over traditional nanomedicine. However, the lack of controllability over an enzymatic process seriously challenges the therapeutic performance. Herein, we present a concept of using piezoelectric enzymes in combination with biocomputation ability. As a paradigm, MnTiO3 nanodisks were prepared with multiple enzyme-mimicking activity, including glutathione oxidase, peroxidase, and catalase. Different from the conventional artificial enzymes, the enzymatic activity of MnTiO3 nanodisks was activated by ultrasound and switched by a tumor microenvironment, which allows precise control over enzymatic catalysis in tumors. By virtue of the multiple artificial enzyme activity of MnTiO3 nanodisks, a biocomputing platform was constructed based on a Boolean logic-based algorithm. With ultrasound and tumor microenvironment as input signals, cytotoxicity was output via logic-based biocomputation for programed tumor killing. The concept of piezoelectric enzymes together with a biocomputation strategy provides an intelligent and effective approach for catalytic tumor eradication.

Mercury contamination is one of the most severe issues in society due to its threats to public health and the ecological system. However, traditional methods for mercury ion detection are still limited by their time-consuming procedures, requirement of expensive instruments, and low selectivity. In recent decades, tremendous progress has been made in the development of functional nucleic acid-based, especially DNAzyme sensors for mercury (Ⅱ) (Hg2+) determination, including RNA-cleaving DNAzymes and G-quadruplex-based DNAzymes in particular. Researchers have heavily studied the construction of Hg2+ sensors, mainly originating from in vitro selection-derived DNAzymes, by incorporating T-Hg2+-T recognition moieties in existing DNAzyme scaffolds, and interfacing Hg2+-sensitive sequences with nanomaterials. In the last case, the employment of materials (as quenchers, signal transducers and DNA immobilizers) enriches the application scenarios of current Hg2+-DNAzymes, due to a combination of their functions. We summarize a broad range of sensing approaches, including optical, electrochemical, and other sensing methods, and compare their features. This review elaborates on the rational design strategies for engineering DNAzymes to selectively sense Hg2+, critically discusses their properties in different application scenarios, and summarizes recent advances in this field. Additionally, current progress, challenges and future perspectives are also discussed. This minireview provides deeper insights into the chemistry of these functional nucleic acids when working with Hg2+, explains the design ideas of DNAzyme-sensors in each platform, and reveals potential opportunities in developing more advanced DNAzyme sensors for the highly selective and sensitive recognition of Hg2+. ENVIRONMENTAL IMPLICATION: Mercury is one of the most toxic metallic contaminants due to its high toxicity, non-biodegradability, and serious human health risks when accumulated in the body. In the recent decade, intensive studies have focused on exploring mercury sensors by combining DNAzymes with various sensing methods, paving a promising avenue to gain ultra-high sensitivity and selectivity. However, so far, no review has introduced the recent advances on DNAzyme-based sensors for mercury detection in a critical way. In this review, we comprehensively summarized the studies on DNAzyme-based sensors for mercury detection using various sensing techniques including optical, electrochemical and other sensing methods.

Bacterial biofilm infections are intractable to traditional antibiotic treatment and usually cause persistent inflammation. Chemodynamic therapy (CDT) based on the Fenton reaction has recently emerged as a promising anti-biofilm strategy. However, the therapeutic efficacy of current Fenton agents often suffers from inefficient Fenton activity and lacks anti-inflammatory capability. Herein, FePS3 nanosheets (NSs) are explored for the first time as novel microenvironment-selective therapeutic nanoagents for bacterial biofilm infections with both self-enhanced Fenton activity for an anti-biofilm effect and reactive oxygen species (ROS) scavenging properties for an anti-inflammatory effect. In biofilms with acidic microenvironments, FePS3 NSs release Fe2+ to generate toxic ROS by Fenton reaction and reductive [P2S6](4-) to enhance the Fenton activity by reducing Fe3+ to Fe2+. In the surrounding normal tissues with neutral pH, FePS3 NSs scavenge ROS by reductive [P2S6](4-) with an anti-inflammatory effect. This work demonstrates multifunctional Fenton nanoagents with microenvironment-selective ROS generation and elimination properties for effective treatment of bacterial biofilm infections with both anti-biofilm and anti-inflammatory effects.