RESUMEN
Although hierarchically porous zeolitic imidazolate frameworks (HPZIFs) not only inherit the intrinsic architectural and chemical stabilities of their microporous counterparts but also afford open space for the efficient mass diffusion of the macromolecules involved, their rational design and construction are still challenging. Herein, HPZIFs with tailorable pore sizes ranging from 18 to 54 nm were successfully fabricated by using a newly developed soft-template-directed strategy. Our success rooted in the fact that the screened PS81-PVP44-PEO113 triblock copolymer could effectively coordinate with the metal precursor for the directed crystallization of ZIFs along surfactant assemblies. The advantages of continuous large pores and open structures in such HPZIFs were fully taken into account to serve as a bioreactor for the efficient immunoassay. The expanded large pores provided not only a significantly vast surface area to enhance the density of capture antibodies but also enough space for accommodating multiple conjugated biomolecules in one pore channel. In combination with a cascade enzyme cycle amplification strategy, a model biomarker of prostate-specific antigen (PSA) at the femtomolar level was checked with a limit of detection of 92 fM using the developed immunosensor. Specific screening on patients with prostate cancer or even benign prostatic hyperplasia was exemplified through accurately quantifying small changes of PSA concentration in clinical serum samples, prefiguring the great potential of the developed HPZIF-8 immunosensor platform for the early monitoring and diagnostics of diseases.
Asunto(s)
Imidazoles , Antígeno Prostático Específico , Zeolitas , Zeolitas/química , Inmunoensayo/métodos , Porosidad , Imidazoles/química , Humanos , Antígeno Prostático Específico/sangre , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/síntesis química , Técnicas Biosensibles/métodos , Límite de DetecciónRESUMEN
Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal-organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.
Asunto(s)
Inflamación , Estructuras Metalorgánicas , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ratones , Superóxido Dismutasa/metabolismo , Porosidad , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células RAW 264.7 , Masculino , Ferroptosis/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Diabetes Mellitus Experimental , Nanopartículas/química , Humanos , Antioxidantes/farmacología , Nanocompuestos/química , Proteínas de la MembranaRESUMEN
In addressing the demand for hierarchically mesoporous metal-organic frameworks (HMMOFs) with adjustable large mesopores, a method based on the synergistic effects of low-temperature microemulsions and Hofmeister ions is developed. Low temperature dramatically enhanced the solubility of hydrophobic solvent in the microemulsion core, enlarging the mesopores in HMMOFs replica. Meanwhile, Hofmeister salt-in ions continuously controlled mesopore expansion by modulating the permeability of swelling agent into the microemulsion core. The large mesopores up to 33 nm provided sufficient space for the alkaline phosphatase (ALP) enrichment, and retained the remaining channel to facilitate the free mass diffusion. Leveraging these advantages, a colorimetric sensor is successfully developed using large-mesopore HMMOFs for femtomolar ALP detection based on the enrichment and cycling amplification principles. The sensor exhibited a linear detection range of 100 to 7500 fm and a limit of detection of 42 fm, presenting over 4000 times higher sensitivity than classic para-nitrophenyl phosphate colorimetric methods. Such high sensitivity highlights the importance of adjustable mesoporous structures of HMMOFs in advanced sensing applications, and prefigures their potential for detecting large biomolecules in diagnostics and biomedical research.
RESUMEN
Although ion-interference therapy (IIT) has become an intriguing option for cancer treatment, the generation of interference ions on-demand remains a challenge. Herein, a nanoplatform based on hierarchically mesoporous metal-organic frameworks (HMMOFs) is adopted to integrate black phosphorus quantum dots (BPQDs) and meso-tetra(4-carboxyphenyl) porphine (TCPP) to realize controllable phosphate anions (PAs) production in a specific cancerous region for IIT. The uniform large mesopores of HMMOFs could guarantee the selective screening and immobilization of ultra-small and monodispersed BPQDs. The TCPP in microporous domains of HMMOFs could effectively produce 1 O2 , which not only serves as photosensitizer for photodynamic therapy (PDT), but also switches on the release of PAs from BPQDs in the adjacent mesoporous domains to trigger the concomitant synergetic IIT. The elaborated nanoplatform (BP@HMUiO-66-TCPP) presents good biocompatibility, biodegradability as well as enhanced synergetic therapeutic effects. In murine models treated with BP@HMUiO-66-TCPP, the tumor inhibition rate is as high as ≈98.24% as compared to that of the control group after 14 days treatment. Moreover, the tumor volumes in the synergetic group are only 19.6% of those in the PDT alone treated group. Such a concept of exogenous photo-controlled synergistic therapeutics might be extended to a broad range of IIT for an improved antitumor efficacy.
Asunto(s)
Estructuras Metalorgánicas , Neoplasias , Fotoquimioterapia , Animales , Iones , Ratones , Neoplasias/terapia , Fosfatos , Fósforo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Diblock copolymer poly(ethylene oxide)-b-poly(styrene) (PEO-b-PS) was adopted to template the synthesis of hierarchically porous Ce-based metal-organic frameworks (MOFs) for the first time. By extending the synergistic effect of Hofmeister ions and soft templates into the water-rich system, UiO-66 type Ce-MOFs with a mesopore size of about 15 nm were achieved. Mesopore size could be further tuned up to approximately 23 nm upon introducing 1,3,5-trimethylbenzene to the micelle core of PEO-b-PS.
RESUMEN
The past few decades have been witnessing the rapid research boom of metal-organic frameworks (MOFs), which are assembled from metal nodes and multitopic organic linkers. In virtue of their modular assembly mode, they can be tailored according to desired functions to satisfy numerous potential applications. However, most initially reported MOFs were restricted to the microporous regime, limiting their practical applications with bulk molecules involved. Therefore, the research attention was immediately directed toward enlarging the intrinsic pore size of frameworks by extending the secondary building units or organic ligands. Unfortunately, the synthesis of more extended ligands is frequently tedious, and the most resultant MOFs are not sufficiently stable, restricting their popularization. The soft-template strategy is recognized as a promising avenue to produce hierarchically porous MOFs (HPMOFs), although early attempts generally failed due to the incompatibility between the surfactant self-assembly and guided crystallization process of MOF precursors in the organic phase. Therefore, developing a rational soft-template strategy to achieve the precise control of morphology and porosity of HPMOFs is of great significance.In this Account, we present our recent progress on the development and applications of HPMOFs prepared by soft-template strategies. We highlight the key issues upon using the soft-template strategy to synthesize HPMOFs. To enhance the interaction between the template and MOF precursor, a long-chain monocarboxylic acid strategy is introduced to synthesize HPMOFs with irregular mesopores in the organic phase. Then, to improve the order of mesopores, an aqueous-phase synthesis method using amphoteric surfactants as templates is developed to prepare ordered HPMOFs. To further enlarge the pore size and make the synthesis conditions of MOFs compatible with the self-assembly of surfactants, a salting-in species-induced self-assembly strategy is proposed and coupled with the structure-directing properties of copolymer templates to synthesize a series of HPMOFs with large mesopores and even macropores. This salting-in ion-mediated self-assembly (SIMS) strategy paves the way to modify the pore size, pore structure, morphology, and chemical composition of HPMOFs. The separated but intimately interconnected hierarchical pores in the resultant HPMOFs can not only realize rapid mass transport but also isolate different-size guest molecules so that they are competent for a broad range of applications including protein digestion, cascade catalysis, enzyme-assisted substrate sensing, and DNA cleavage. Finally, the limitations, challenges, and future developments of this rapidly evolving field are described. This Account with a highlight to the soft-template strategies not only provides interesting insights to understand the assembly process between templates and MOFs but also inspires an optimization of the properties of HPMOFs from diverse aspects for desired applications.
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Estructuras Metalorgánicas , Catálisis , Ligandos , Estructuras Metalorgánicas/química , Metales , Porosidad , TensoactivosRESUMEN
As one of the most appealing strategies for the synthesis of nanomaterials with various architectures, emulsion-directed methods have been rarely used to control the structure of metal-organic frameworks (MOFs). Herein, we report a versatile salt-assisted nanoemulsion-guided assembly to achieve continuous architecture transition of hierarchical Zr-based MOFs. The morphology of nanoemulsion can be facilely regulated by tuning the feed ratio of a dual-surfactant and the introduced amount of compatible hydrophobic compounds, which directs the assembly of MOFs with various architectures such as bowl-like mesoporous particle, dendritic nanospheres, walnut-shaped particles, crumpled nanosheets and nanodisks. The developed dendritic nanospheres with highly open and large mesochannels is successfully used as matrix for the co-immobilization of coenzymes and corresponding enzymes to realize the in situ heterogeneous regeneration of NAD+. This strategy is expected to pave a way for exploring sophisticated hierarchical MOFs which can be competent for practical applications with bulk molecules involved.
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Estructuras Metalorgánicas , Nanoestructuras , Coenzimas , Emulsiones , Estructuras Metalorgánicas/químicaRESUMEN
Despite the fact that bimetallic metal-organic frameworks (MOFs) could afford multiple functionalities by a synergistic effect of individual metallic centers, their intrinsic microporous structure frequently restricts their wide applications with bulky molecules involved. An urgent need is consequently triggered to design bimetallic hierarchical mesoporous MOFs (mesoMOFs). Herein, Zr/Ce mesoMOFs with a uniform pore size of up to 8 nm was successfully synthesized by a copolymer template strategy with the aid of a Hoffmeister ion. The obtained Zr/Ce mesoMOFs feature high porosity, good chemical and thermal stabilities, and tunable element components, and up to 70% Zr could be incorporated into the mesoporous Ce-based framework without deteriorating its crystallinity. Thanks to the synergistic effect of inherent Ce and Zr as well as the large and open pore channels, a broad range of phosphopeptides with different molecule sizes could be effectively checked out, thanks to their simultaneous enrichment and dephosphorylation capabilities. Such an ability to efficiently concentrate phosphopeptides remained intact even in the presence of abundant non-phosphorylated species. The practical detection of phosphopeptides from human serum was also verified, prefiguring the great potentials of bimetallic large-pore mesoMOFs for the proteome applications.
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Cerio/química , Estructuras Metalorgánicas/química , Fosfopéptidos/síntesis química , Circonio/química , Humanos , Ensayo de Materiales , Tamaño de la Partícula , Fosfopéptidos/sangre , Fosfopéptidos/química , Fosforilación , Porosidad , Propiedades de SuperficieRESUMEN
The construction of a biomimetic ionic channel is of great significance for the fabrication of smart biodevices or logic circuit. Inspired by the selective permeability of the cell membrane toward bioions, a light-induced and pH-modulated artificial nanochannel is herein prepared by integrating the multistimuli-response molecule of carboxylated spiropyran (SP-COOH) into the frameworks of NU-1000 (Zr-based MOFs defined by Northwestern University). The loading density of the SP-COOH could reach as high as 7 wt % while keeping unchanged crystallinity and high porosity. Thanks to the precise matching of pore size of NU-1000 and molecular dimensions of SP-COOH, the loaded molecules could proceed free and reversible for isomerization between the hydrophilic and hydrophobic states. The ion-switchable characteristics of the channel are implemented by the amphiphilic change of the light-controlled gate molecule. Additionally, in the hydrophilic state, the channel presents reversible affinity toward cations or anions due to the reverse charge state induced by pH, thus constructing a pH-controlled subgate. Taking [Ru(NH3)6]3+ and [Fe(NH3)]3- as the model cation and anion, their redox peak currents occur as reversible change under different signal combinations of light and pH. Moreover, in accordance with the ionic selective permeability, several logic circuits/devices are designed to display the relationships between exogenous stimuli and ionic transportations in a computer language, prefiguring their wide application prospects in electronic devices and life sciences.
RESUMEN
Rapid and specific identification of tumor metabolic markers is of great significance. Herein, a convenient, reliable and specific strategy was proposed to screen prostate cancer (PCa) individuals through indirectly quantifying sarcosine, an early indicator of PCa, in the clinical urine samples. The success roots in the rational design of a cascade response model, which takes integrated sarcosine oxidase (SOX) as a specific recognition unit and oxygen-sensitive molecule as a signal reporter. The newly developed hierarchical mesoporous Zr-based metal-organic frameworks with continuously tunable mesopore size ensure the synergetic work of the SOX and response unit spatially separated in their neighboring mesoporous and microporous domains, respectively. The large mesopore up to 12.1 nm not only greatly enhances the loading capacity of SOX but also spares enough space for the free diffusion of sarcosine. On this basis, the probe is competent to specifically check out the tiny concentration change of sarcosine in the urine sample between PCa patients and healthy humans. Such a concept of enzyme-assisted substrate sensing could be simply extended by altering the type of immobilized enzymes, hopefully setting a guideline for the rational design of multiple probes to quantify specific biomarkers in complex biological samples.
Asunto(s)
Técnicas Electroquímicas/métodos , Estructuras Metalorgánicas/síntesis química , Neoplasias de la Próstata/diagnóstico , Biomarcadores de Tumor , Humanos , Límite de Detección , Masculino , Estructuras Metalorgánicas/química , Modelos Moleculares , Estructura Molecular , Sarcosina-Oxidasa/química , Sarcosina-Oxidasa/metabolismoRESUMEN
Highly evolved substrate channels in natural enzymes facilitate the rapid capture of substrates and direct transfer of intermediates between cascaded catalytic units, thus rationalizing their efficient catalysis. In this study, a nanoscale ordered mesoporous Ce-based metal-organic framework (OMUiO-66(Ce)) is designed as an artificial substrate channel, where MnO2 is coupled to Ce-O clusters as a super-active catalase (CAT). An in situ soft template reduction strategy is developed to deposit well-dispersed and exposed MnO2 in the mesochannels of OMUiO-66(Ce). Several synthesis parameters are optimized to minimize the particle size to ≈150 nm for efficient intracellular endocytosis. The mesochannels provide interaction guidance that not only rapidly drove H2 O2 substrates to CAT-like catalytic centers, but also seamlessly transfer H2 O2 intermediates between superoxide dismutase-like and CAT-like biocatalytic cascades. As a result, the biomimetic system exhibits high efficiency, low dosage, and long-lasting intracellular antioxidant function. Under disease-related oxidative stress, the artificial substrate channels promote the rate of the reactions catalyzed by MnO2 , which exceeds that of the reactions catalyzed by natural CAT. Based on this observation, a set of design rules for substrate channels are proposed to guide the rational design of super-active biomimetic systems.
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Compuestos de Manganeso , Metaloproteínas , Biomimética , Catálisis , ÓxidosRESUMEN
A bifunctional metal-organic framework (MOF) was successfully designed to realize the purification of 4-chlorophenol (4-CP) under simulated sunlight irradiation. Owing to the large-size mesopores of the MOF matrix NU-1000, ß-CMCD (carboxylic ß-cyclodextrin) could be incorporated into the frameworks with a density of 2.4% to pre-enrich the pollutant of 4-CP. Meanwhile, the photodegradation promoter [Pd(II) meso-tetra(4-carboxyphenyl)porphine] was in situ co-assembled with the organic ligand to realize its synchronous degradation. As for the current integrator, a Langmuir model was used to explain the adsorption isotherm, and the Langmuir-Hinshelwood model exhibited a better fit to its catalytic degradation behavior. Thanks to the simultaneous presence of a capturer and a photodegradation promoter, the adsorption capacity of 4-CP reached as high as 296 mg g-1, which was further completely detoxified within 60 min under simulated sunlight irradiation with a half-life time of only 5.98 min. Such excellent integrated decontamination properties prefigure the great promising potential of multifunctional MOFs in the field of pollution purification.
RESUMEN
Efficient decontamination of radioactive Ba2+ is of great significance to human health and environmental safety. Herein, an adsorbent based on the sulfonic acid functionalized Zr-MOF has been successfully developed, which could efficiently decontaminate radioactive Ba2+ with excellent selectivity, recyclability, a high adsorption capacity up to 60.8 mg g-1 as well as a short adsorption kinetic time of less than 5 min. This outstanding adsorption performance is attributed to the strong affinity between Ba2+ and high density -SO3H active sites in MOFs which were introduced by an in situ ligand modification strategy during the assembly of MOFs.
Asunto(s)
Radioisótopos de Bario/aislamiento & purificación , Estructuras Metalorgánicas/química , Ácidos Sulfónicos/química , Circonio/química , Radioisótopos de Bario/química , Estructuras Metalorgánicas/síntesis químicaRESUMEN
Apyrase is an important family of extracellular enzymes that catalyse the hydrolysis of high-energy phosphate bonds (HEPBs) in ATP and ADP, thereby modulating many physiological processes and driving life activities. Herein, we report an unexpected discovery that cerium-based metal-organic frameworks (Ce-MOFs) of UiO-66(Ce) have intrinsic apyrase-like activity for ATP/ADP-related physiological processes. The abundant CeIII /CeIV couple sites of Ce-MOFs endow them with the ability to selectively catalyse the hydrolysis of HEPBs of ATP and ADP under physiological conditions. Compared to natural enzymes, they could resist extreme pH and temperature, and present a broad range of working conditions. Based on this finding, a significant inhibitory effect on ADP-induced platelet aggregation was observed upon exposing the platelet-rich plasma (PRP) to the biomimetic UiO-66(Ce) films, prefiguring their wide application potentials in medicine and biotechnology.
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Adenosina Difosfato/metabolismo , Adenosina Trifosfato/antagonistas & inhibidores , Cerio/farmacología , Estructuras Metalorgánicas/farmacología , Cerio/química , Estructuras Metalorgánicas/química , Modelos Moleculares , Estructura Molecular , Fosforilación/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacosRESUMEN
Commercial nickel nanoparticles (Ni NPs) were directly converted to efficient electrocatalysts for CO2 reduction by urea-Ni solid powder pyrolysis, in which a Ni, N-co-doped graphite carbon shell wraps the Ni NPs in situ. 98.3% CO selectivity was realized with a current density of -20.2 mA cm-2 and an overpotential of 0.69 V.
RESUMEN
Enzyme-activated prodrug therapy (EAPT) is an effective cancer treatment strategy able to transport non-toxic prodrugs and subsequently convert them into drugs at specific times and locations. However, due to the limitation of easy biodegradability and the membrane-impermeable characteristic of exogenous enzymes, there is a need to exploit suitable carriers for the effective protection and simultaneous delivery of activating enzymes into cancer cells. Herein, hierarchically porous MOFs were employed for the loading of enzyme and prodrug in a single nanocarrier thanks to their different cavity sizes. The simple loading process allows entrapping of horseradish peroxidase (HRP) and a monocarboxyl-containing indole-3-acetic acid (IAA) prodrug with high loading capacities in different spaces, which keeps the catalytic activity of the enzyme perfectly intact and avoids the premature activation of the prodrug. The encapsulated HRP and IAA exhibit sustained and synchronized release behaviors. Compared to the native HRP enzyme, the current MOF nanocarriers not only facilitate enzyme delivery into cellular lysosomes and subsequent endosomal escape, but also effectively release enzyme and prodrug in the intracellular environment within 48 h. Eventually, HRP and IAA loaded MOF nanocarriers cause significant cell death with a low IC50 of 4.2 mg L-1, while the IAA prodrug alone is non-toxic even at high concentrations. Thus, hierarchically porous MOFs might offer a promising platform for EAPT with a highly consistent spatiotemporal distribution of enzymes and prodrugs in target tissues.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/terapia , Terapia Enzimática , Peroxidasa de Rábano Silvestre/metabolismo , Ácidos Indolacéticos/farmacología , Neoplasias Hepáticas/terapia , Profármacos/farmacología , Antineoplásicos/química , Antineoplásicos/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Peroxidasa de Rábano Silvestre/química , Humanos , Ácidos Indolacéticos/química , Ácidos Indolacéticos/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/metabolismo , Estructura Molecular , Nanopartículas/química , Nanopartículas/metabolismo , Tamaño de la Partícula , Profármacos/química , Profármacos/metabolismo , Propiedades de Superficie , Células Tumorales CultivadasRESUMEN
Ordered mesoporous metal-organic frameworks (mesoMOFs) were constructed with a uniform pore size up to about 10â nm and thick microporous walls, opening up the possibility for the mass diffusion of large-size molecules through crystalline MOFs. The synergistic effects based on triblock copolymer templates and the Hofmeister salting-in anions promote the nucleation of stable MOFs in aqueous phase and the inâ situ crystallization of MOFs around templates, rendering the generation of a microcrystal with periodically arranged large mesopores. The improved mass transfer benefiting from large-pore channels, together with robust microporous crystalline structure, endows them as an ideal nanoreactor for the highly efficient digestion of various biogenic proteins. This strategy could set a guideline for the rational design of new ordered large-pore mesoMOFs with a variety of compositions and functionalities and pave a way for their potential applications with biomacromolecules.
RESUMEN
A glutathione-triggered drug delivery system (DDS) based on nanoscale metal-organic frameworks (NMOFs) is developed, which features an intracellular redox-responsive release of an anticancer drug. Compared to normal cells, the current NMOF-based DDS has 3-fold higher cytotoxicity to cancer cells, prefiguring its great potential for selective cancer therapy.
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Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos , Glutatión/química , Mercaptopurina/farmacología , Estructuras Metalorgánicas/química , Nanopartículas/química , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Mercaptopurina/administración & dosificación , Mercaptopurina/química , Microscopía Confocal , Imagen Óptica , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Exploring innovative technologies to precisely quantify biomolecules is crucial but remains a great challenge for disease diagnosis. Unfortunately, the humoral concentrations of most biotargets generally vary within rather limited scopes between normal and pathological states, while most literature-reported biosensors can detect large spans of targets concentrations, but are less sensitive to small concentration changes, which consequently make them mostly unsatisfactory or even unreliable in distinguishing positives from negatives. Herein, a novel strategy of precisely quantifying the small concentration changes of a certain biotarget by editing the dynamic ranges and sensitivities of a lanthanide-based metal-organic framework (Eu-ZnMOF) biosensor is reported. By elaborately tailoring the biosensor's structure and surface areas, the tunable Eu-ZnMOF is developed with remarkably enhanced response slope within the "optimized useful detection window," enabling it to serve as a powerful signal amplifier (87.2-fold increase) for discriminating the small concentration variation of urinary vanillylmandelic acid (an early pathological signature of pheochromocytoma) within only three times between healthy and diseased subjects. This study provides a facile approach to edit the biosensors' performances through structure engineering, and exhibits promising perspectives for future clinical application in the non-invasive and accurate diagnosis of severe diseases.