Aung Than

Natural enzymes are widely used in theranostics, but they suffer from poor stability, high costs, and nontunable monofunctionality, driving the development of artificial enzymes, in particular single-atom nanozymes (SAzymes). However, conventional SAzymes struggle to handle multistep redox reactions effectively. Herein, we present atomically dispersed zinc−phosphorus (Zn−P) catalytic pairs (CPs) anchored on acid-resistant carbon nanosheets (Zn−P/CNS) that display greatly enhanced multienzyme-like activities, particularly for superoxide radical dismutation and hydrogen peroxide decomposition. Density functional theory reveals that P primarily serves as an additional catalytic site to facilitate substrate binding and intermediate stabilization, while also modulating the local electronic structure of Zn and aiding proton transfer, thereby lowering energy barriers in the multistep redox pathways. In a dextran sulfate sodium-induced colitis model, oral administration of this Zn−P/CNS markedly reduces oxidative damage and inflammation, demonstrating the promise of metal−nonmetal CPs as a versatile platform for designing high-performance nanozymes for biomedical applications.

Artificial urinary biomarker probes (AUBPs) have recently emerged as a new class of diagnostic tools. However, they are applicable only to the biomarkers with catalytic activities or high reactivities. Here, we present a general modular design of AUBPs, integrating an aptamer for target recognition, DNAzyme for triggerable signal transduction, and nanozyme as a urinary artificial biomarker. For proof-of-concept demonstration, we developed an AUBP that is specifically and sensitively responsive to circulating an amyloid-β oligomer (AβO). After the nanoprobe was injected into circulation, colorimetric urinalysis was conducted to infer the circulating level of AβO for early diagnosis of Alzheimer's disease (AD). This approach can unambiguously distinguish AD mice from healthy ones, achieving a low detection limit of ∼2.8 pg/mL. It is ∼67 times more sensitive than the conventional enzyme-linked immunosorbent assay, owing to the cascaded signal amplification enabled by DNAzyme activity, enrichment by renal filtration, and chromogenic reaction catalyzed by nanozyme.

Despite the increasing prevalence of obesity, the current medications, which act indirectly on the central nervous system to suppress appetite or on the gastrointestinal tract to inhibit fat absorption, suffer from poor effectiveness and side effects. Here, we developed a transdermal mild photothermal therapy directly acting on the root of evil (subcutaneous white adipose depot) to induce its ameliorating remodeling (browning, lipolysis, and apoptosis), based on the injectable thermoresponsive hydrogel encapsulated with copper sulfide nanodots. Further, combining pharmaceutical therapy with codelivery of mirabegron leads to a strong therapeutic synergy. This method not only ensures high effectiveness and low side effects due to localized and targeted application but also remotely creates significant improvements in systemic metabolism. Specifically, as compared to the untreated group, it totally inhibits obesity development in high-fat-diet fed mice (15% less in body weight) with decreased masses of both subcutaneous (40%) and visceral fats (54%), reduced serum levels of cholesterol (54%)/triglyceride (18%)/insulin (74%)/glucose (45%), and improved insulin sensitivity (65% less in insulin resistance index). This self-administrable method is amenable for long-term home-based treatment. Finally, multiple interconnected signaling pathways are revealed, providing mechanistic insights to develop effective strategies to combat obesity and associated metabolic disorders.

Obesity is a serious epidemic health problem that can cause many other diseases including type 2 diabetes and cardiovascular diseases. Current approaches to combat obesity suffer from low effectiveness and adverse side effects. Here, a new self‐administrable and minimally invasive transdermal drug delivery strategy for home‐based long‐term treatment of obesity and other diseases is developed. Specifically, ultrathin, core‐shelled, and lance‐shaped polymeric drug reservoirs (micro‐lances [MLs]) are readily fabricated by a thermal pressing molding method and totally implanted into subcutaneous fat by lancing through the skin. Using a diet‐induced obese mouse model, it is shown that the development of obesity and associated metabolic disorders is effectively inhibited by applying therapeutic core‐shelled MLs once every 2 weeks. The outstanding therapeutic effects are attributable to highly localized and biphasic drug release, as well as combination therapy based on browning transformation of white fat and enhanced insulin sensitivity.

Skin offers an easily accessible site for drug administration as well as for health signal monitoring, with non‐invasiveness or minimal‐invasiveness, convenience, and good patient compliance. Transdermal theranostics promises for personalized, home‐based, and long‐term management of chronic diseases, and is expected to change the landscape of healthcare profoundly. In this article, we review the recent advances in transdermal drug delivery, diagnosis based on sweat and skin interstitial fluid, and wearable devices. The advantages, limitations, and commercialization of these emerging techniques are comparatively discussed.

Monitoring cellular redox homeostasis is critical to the understanding of many physiological functions ranging from immune reactions to metabolism, as well as to the understanding of pathological development ranging from tumorigenesis to aging. Nevertheless, there is currently a lack of appropriate probes for this ambition, which should be reversibly, sensitively, and promptly responsive to a wide range of physiological oxidants and reductants. In this work, a redox-sensitive fluorescence-switchable probe is designed based on graphene quantum dots (GQDs) functionalized with a chelated redox Fe²⁺/Fe³⁺ couple. The underlying mechanism is investigated and discussed. The high sensitivity and fast response are attributable to the fact that the GQD’s photoluminescence is highly sensitive to photon-induced electron transfer because of its ultrasmall size and associated prominent quantum confinement effect. Also taking advantages of GQDs’ excellent photostability, biocompatibility, and readiness for cell uptake, our reversibly tunable fluorescence probe is employed to monitor in real time the triggered dynamic change of the intracellular redox state. This addition to the limited arsenal of available redox probes shall be useful to the still poorly understood redox biology, as well as for monitoring environment or chemical processes involving redox reactions.

In this work, we present a new type of polymer dot synthesized from bithiophene (pTh-Pdot) via a simple and high yield procedure. Owing to their high brightness, excellent photo-stability, good biocompatibility, and molecular size, pTh-Pdots are promising for bioimaging applications. As a proof-of-concept demonstration, pTh-Pdots are herein employed to track the endocytic pathway in live cells. Furthermore, we show that these polymeric nanoparticles can serve as potent antibacterial agents by making use of their ability to disrupt bacterial membranes and high peroxidase mimicking activity.

Graphene quantum dots (GQDs) are emerging fluorescence reporters attractive for optical sensing, owing to their high photostability, highly tunable photoluminescence, molecular size, atomically thin structure, biocompatibility, and ease of functionalization. Herein, we present a fluorometric sensing platform based on tyramine-functionalized GQDs, which is able to detect a spectrum of metabolites with high sensitivity and specificity. Furthermore, multiparametric blood analysis (glucose, cholesterol, l-lactate, and xanthine) is demonstrated. This convenient metabolite profiling technique could be instrumental for diagnosis, study, and management of metabolic disorders and associated diseases, such as diabetes, obesity, lactic acidosis, gout, and hypertension.