Yuehe Lin

Monoclonal antibodies (mAbs) underpin modern treatment of cancer, autoimmune, and chronic inflammatory disease, yet systemic administration remains pharmacologically inefficient, requiring high circulating doses that raise off-target toxicity and waste costly biologics. This review organizes the material- and device-based delivery systems developed over the past five years along a materials-to-devices axis spanning inorganic and organic nanocarriers, stimuli-responsive hydrogels, microneedles, and integrated device platforms. Across these platforms, controlled release is achieved primarily through size exclusion via engineered pore structures or by tuning the degradation rate of the encapsulating matrix, while stimuli-responsive chemistries add temporal-spatial control through phase, conformational, or degradation changes triggered by internal or external cues. The review assesses progress across a consistent set of criteria spanning payload performance, biocompatibility, tissue penetration, manufacturability, and regulatory readiness. We find that material systems lead in loading capacity and release control while device platforms lead in tissue penetration and programmable, feedback-controlled dosing, with localized delivery consistently lowering peak systemic exposure relative to free-antibody administration. However, progress is uneven: carrier biocompatibility and long-term in vivo safety remain incompletely characterized across platform classes, and antibody bioactivity can be compromised by the same stimuli used to trigger release. Manufacturability and regulatory readiness are the least developed dimensions across every platform class, forming the primary bottleneck to clinical translation, particularly for combination products that single-function regulatory frameworks do not accommodate. Advancing the field will require head-to-head trials against standard-of-care injections, long-term safety and adherence data, scalable cGMP manufacturing, dedicated regulatory pathways, and standardized assays for antibody bioactivity under device-activation conditions.

Flexible electrochemical sensors have emerged as a promising platform for real-time, noninvasive health monitoring, driven by rapid advances in nanomaterials, fabrication methods, and system integration. Over the past decade, substantial efforts have focused on improving their mechanical flexibility, analytical sensitivity, and biocompatibility, thereby expanding their potential in clinical diagnostics and personalized healthcare. Despite this progress, several key challenges continue to hinder practical translation. This review provides a comprehensive overview of recent advances in flexible electrochemical sensors, with particular emphasis on nanomaterial engineering, device fabrication strategies, and biomedical applications. Representative applications in sweat, interstitial fluid, tears, and saliva are summarized and critically discussed. The review also examines current limitations, including challenges in sample collection, the variable reliability of biofluid biomarkers, and interference from complex biological matrices. Finally, future perspectives are presented on the integration of artificial intelligence and machine learning with flexible electrochemical sensors to enable improved data interpretation, interference correction, and more accurate biomarker identification in complex biofluids.

As alternatives to bioenzymes, nanozymes find promising applications in biochemical sensing thanks to their recognized superiorities, but their lack of specific interactions with targets of interest seriously hinders the exploration of selective analytical strategies when no external receptors are employed. Additionally, most nanozymes exhibit poor catalytic efficiency, much lower than their natural counterparts, thus restricting the sensitivity of detection. Different from the explored “turn-off” analytical principle relying on the coordination of the target with a nanozyme catalytic product, here we proposed an analyte-unique “signal-on” strategy based on the direct target–nanozyme interaction for the sensitive sensing of uranyl via temperature-programming the peroxidase (POD)-mimetic activity of CoOx. As wet-chemical temperature increased, the oxygen vacancy (OV) content on CoOx surfaces exhibited a volcano-type trend, and its catalytic efficiency correlated with the former positively. UO22+ was found to stimulate the POD-like activity of CoOx via increasing OV, exhibiting excellent specificity against other common species. Leveraging the unique CoOx–UO22+ interaction and the temperature-programmed activity of CoOx, we validated a “light-up” colorimetric approach for UO22+ selective determination, achieving a wide detection range (0.01–2 μM) and a low limit (5 nM). A deployable device based on intelligent reading was further fabricated to enable on-site monitoring of the analyte. Our work provides a “signal-on” nanozyme sensing strategy for the quantification of UO22+, featuring specific response, catalytic signal amplification, and free from bioreceptors. Also, it proves a facile route to achieve dual modulation of enzyme-mimetic activity and analyte response for broader applications.

Compared with oxidoreductase mimics, hydrolase-like nanozymes can circumvent the interference from redox species in real matrices, exhibiting unique superiority for biochemical sensing, but insufficient catalytic efficiency and lack of specific response to targets when no bioreceptor (aptamer, antibody, etc.) is employed greatly restrict their advanced analytical applications. To solve this predicament, here we employed a ligand engineering strategy to modulate the phosphatase-mimetic activity of Nd(III)-coordinated phenylboronic acid (PBA) derivatives and achieved anti-interference and sensitive detection of quinolone antibiotics in dairy products based on matched interaction and ligand-optimized catalytic efficiency. By tailoring the ortho-substituted PBA ligand, precise activity control was obtained through adjusting surface Lewis acidity and substrate adsorption jointly. Quinolones could specifically suppress the activity of Nd-PBA via strong hydrogen bonding, π–π stacking, and coordination interactions, allowing the nanozyme to function as both recognition unit and signal transducer without the need for external bioreceptors. According to the principle, high-performance sensing of ciprofloxacin as a quinolone model was validated. By leveraging the synergy of specific interaction and hydrolase-mimicking catalytic nature, the established approach exhibited good anti-interference capability in complex matrices. The ligand-modulated catalytic activity provided sufficient sensitivity for detecting the analyte in dairy products. Our attribution not only develops a new hydrolase mimic with engineerable phosphatase-like catalytic characteristics via ligand programming but also offers a rarely explored approach for selectively detecting quinolone antibiotic residues, inspiring future design of bioreceptor-free nanozyme sensing systems for broader applications.

Electrochemical sensors have attracted considerable attention due to their rapid response and high sensitivity. In this work, CuCo binary alloy catalysts were synthesized via a co-precipitation method and applied to amperometric ammonia sensing. Compared with conventional Pt-based catalysts, the CuCo alloys exhibit high catalytic activity and strong resistance to poisoning by reaction intermediates generated during ammonia oxidation. This enhanced performance is attributed to the synergistic interaction between Cu and Co, as well as electron redistribution at the Cu-Co interface, which modulates the adsorption of reaction intermediates and suppresses surface poisoning. Among the synthesized catalysts, the 1Cu9Co@C sample delivered the best electrochemical performance. It showed a linear response to ammonia concentrations from 5 to 240 μM, with a sensitivity of 18 μA mM ⁻¹ and a detection limit of 1.5 μM. These results suggest that CuCo alloy catalysts are efficient and low-cost materials for achieving sensitive and reliable electrochemical ammonia detection.

Nanozymes, nanoscale materials with intrinsic enzyme-like catalytic properties, have emerged as promising candidates for analytical detection due to their high stability, low cost, and tunable design. Early research primarily focused on redox-active nanozymes, which demonstrated remarkable success in fabricating optical and electrochemical sensing platforms for use in environmental monitoring, food safety analysis, and biomarker detection. However, redox reactions are susceptible to matrix interference and exhibit limited capability for directly detecting non-redox targets. To expand the applicability of nanozymes, recent studies have shifted attention towards hydrolase-mimicking nanozymes, particularly those capable of catalyzing the hydrolysis of phosphate esters. These nanozymes enable the specific cleavage of phosphate ester bonds, providing unique signal transduction principles for the direct detection of phosphorylated biomolecules, organophosphorus pesticides, and nerve agents. In this minireview, we summarize the latest advances in phosphatase-mimetic nanozymes, with a focus on their emerging applications in food analysis, biomedical sensing, and ion detection. In addition, the catalytic mechanisms of phosphatase-mimetic nanozymes are discussed, and material components that can mimic the hydrolytic activity are summarized. Current challenges in this promising field and future development trends are also pointed out. We aim to offer some insights into the rational design and functional modulation of phosphatase-mimetic nanozymes, facilitating their practical implementation in analytical sensing.

Melatonin secretion by the pineal gland occurs predominantly at night, although ocular exposure to bright light suppresses its secretion. When measured under dim light conditions, the melatonin concentration in plasma provides a reliable indicator of the state of an individual's central circadian pacemaker in the hypothalamus. Specifically, the onset of melatonin secretion in the evening, conventionally defined as the time when the plasma concentration surpasses a threshold of 10 pg mL⁻¹, serves as a gold-standard measure of the start time of physiological night. Current melatonin detection methods typically require expensive assays and instrumentation as well as trained personnel, or they lack sufficient sensitivity and anti-interference capabilities, which limit their use in point-of-need settings. To address these challenges, we developed a europium nanoparticle-based lateral flow immunoassay (EuNP-LFIA) integrated with a 3D-printed smartphone-based fluorescence reader for on-site melatonin detection in plasma. Six key parameters, namely readout time, EuNP size, antibody conjugation level, Tween-20 concentration, EuNP deposition volume, and the concentration of melatonin–bovine serum albumin on the nitrocellulose membrane, were systematically optimized. Upon optimization, the sensing platform exhibited highly sensitive detection of melatonin in buffer solution and achieved a limit of detection (LOD) of 9.99 pg mL⁻¹. For melatonin-spiked plasma samples, the recovery rates ranged from 82.58% to 114.70%, indicating excellent repeatability and reliability. Overall, the proposed method possesses high sensitivity and accuracy, offering a portable, rapid (<15 min), cost-effective, and user-friendly solution for real-time monitoring of plasma melatonin.

Advances in nanotechnology have facilitated the emergence of diverse nanozymes. Photo-regulated nanozymes represent a unique class of enzyme mimics with their activities being precisely modulated by irradiation. The distinct catalytic mechanisms of photo-regulated nanozymes enable their versatile applications across multiple fields, particularly in sensing. However, the low catalytic efficiency of most photo-regulated nanozymes limits their practical application. Designing advanced photo-regulated nanozymes is promising, yet achieving this remains a great challenge. In this review, the catalytic mechanisms of photo-regulated nanozymes are systematically introduced, and several effective strategies for the rational design of advanced photo-regulated nanozymes are also highlighted. Furthermore, we summarize the recent advances of photo-regulated nanozymes in sensing and discuss the potential challenges and the corresponding strategies in their development. It is believed that this review can revolutionize the design concepts of photo-regulated nanozymes and expand their prospects in sensing applications.

Wearable electrochemical sensors have aroused tremendous attention due to their great potential for in situ and continuous assessment for glucose monitoring. The conventional fingerstick test is the easiest and most efficient method for glucose evaluation, but it is invasive and painful. Here we introduce a wearable and user-friendly microneedle-based electrochemical sensor, fabricated via resin 3D printing with an affordable desktop 3D printer and featuring a single-atom nanozyme-modified electrode, offering high sensitivity and superior selectivity for glucose monitoring. This minimally invasive electrochemical sensor demonstrates the capability to extract artificial interstitial fluid using hollow microneedles and a finger-activated pump, enabling continuous monitoring of dynamic glucose concentration changes. This electrochemical sensor exhibits remarkable sensitivity and selectivity, with a linear range of 0.1 μM to 50 mM and a limit of detection of 0.285 μM, attributed to the incorporation of single-atom nanozymes with peroxidase-like enzymatic activity. The glucose concentration data are wirelessly transmitted to a smartphone application in real time, offering user-friendly access and facilitating remote monitoring. The described electrochemical sensor presents the possibilities for point-of-care health monitoring applications.