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Sodium-ion battery (SIB) is one of potential alternatives to lithium-ion battery, because of abundant resources and lower price of sodium. High electrical conductivity and long-term durability of MXene are advantageous as the anode material of SIB, but low energy density restricts applications. Tin phosphide possesses high theoretical capacity, low redox potential, and large energy density, but volume expansion reduces its cycling stability. In this study, tin phosphide particles are in-situ encapsulated into MXene conductive networks (SnxPy/MXene) by hydrothermal and phosphorization processes as novel anode materials of SIB. MXene amounts and hydrothermal durations are investigated to evenly distribute SnxPy in MXene. After 100 cycles, SnxPy/MXene reaches high specific capacities of 438.8 and 314.1 mAh/g at 0.2 and 1.0 A/g, respectively. The capacity retentions of 6.0% and 73.6% at 0.2 A/g are respectively obtained by SnxPy and SnxPy/MXene. The better specific capacity and cycling stability of SnxPy/MXene are attributed to less volume expansion of SnxPy during charge/discharge processes and relieved self-stacking of MXene by encapsulating SnxPy particles between MXene layers. Electrochemical impedance spectroscopy and Galvanostatic intermittent titration technique are also applied to analyze the charge storage mechanism in SIB. Higher sodium ion diffusion coefficient and smaller charge-transfer resistance are obtained by SnxPy/MXene.
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We have experimentally validated the use of sensorless adaptive optics (AO) to enhance laser scanning confocal microscopy in the second near-infrared (NIR II) spectral range, termed as AO-NIR II confocal microscopy. This approach harnesses a NIR II fluorophore, excited by an 808â nm wavelength and emitting beyond 1000â nm, to visualize intricate structures in deep brain tissues with the intact skull. By leveraging the reduced scattering and aberrations in the NIR II spectrum, we successfully captured a three-dimensional (3D) vascular structure map extending 310â µm beneath the skull. AO typically boosts the fluorescence signal by approximately 2-3 times, leading to a superior contrast and diminished smearing effects. Consequently, small blood vessels at various depths can be clearly visualized, which might otherwise remain undetectable without AO corrections.
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Microscopía Confocal , Microscopía Confocal/métodos , Animales , Rayos Infrarrojos , Encéfalo/diagnóstico por imagen , Encéfalo/irrigación sanguínea , Vasos Sanguíneos/diagnóstico por imagen , Ratones , Imagenología Tridimensional/métodos , Imagen Óptica/métodosRESUMEN
Photoacoustic imaging (PAI) can sensitively detect regions and substances with strong optical absorption, which means that diseased tissue can be imaged with high contrast in the presence of surrounding healthy tissue through the photoacoustic effect. However, its signal intensity and resolution may be limited by background signals generated by endogenous chromophores such as melanin and hemoglobin. A feasible method for practical application of this so-called background-suppressed PAI is still lacking. In this work, a dual-wavelength differential background noise-suppressed photoacoustic tomography is developed based on organic semiconducting polymer dots (Pdots). The Pdots have a strong absorption peak at 945 nm, and then the absorption decreases sharply with the increase of wavelength, and the absorption intensity drops to only about a quarter of the original value at 1050 nm. The present system significantly suppresses the strong background noise of blood through dual-wavelength differential PAI, enabling precise monitoring of the distribution information of theranostic agents in diseased tissues. The signal-to-noise ratio of the theranostic agent distribution map is increased by about 20 dB. This work provides a platform for real-time and accurate monitoring of tumors and drugs, which helps avoid damage to healthy tissue during treatment and has clinical significance in cancer treatment.
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We describe small heterojunction polymer dots (Pdots) with deep-red light catalyzed H2 generation for diabetic skin wound healing. The Pdots with donor/acceptor heterojunctions showed remarkably enhanced photocatalytic activity as compared to the donor or acceptor nanoparticles alone. We encapsulate the Pdots and ascorbic acid into liposomes to form Lipo-Pdots nanoreactors, which selectively scavenge â OH radicals in live cells and tissues under 650â nm light illumination. The antioxidant capacity of the heterojunction Pdots is ~10â times higher than that of the single-component Pdots described previously. Under a total light dose of 360â J/cm2, the Lipo-Pdots nanoreactors effectively scavenged â OH radicals and suppressed the expression of pro-inflammatory cytokines in skin tissues, thereby accelerating the healing of skin wounds in diabetic mice. This study provides a feasible solution for safe and effective treatment of diabetic foot ulcers.
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Diabetes Mellitus Experimental , Hidrógeno , Luz , Polímeros , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Hidrógeno/química , Animales , Ratones , Polímeros/química , Humanos , Puntos Cuánticos/química , Luz RojaRESUMEN
Practical photodynamic therapy calls for high-performance, less O2-dependent, long-wavelength-light-activated photosensitizers to suit the hypoxic tumor microenvironment. Iridium-based photosensitizers exhibit excellent photocatalytic performance, but the in vivo applications are hindered by conventional O2-dependent Type-II photochemistry and poor absorption. Here we show a general metallopolymerization strategy for engineering iridium complexes exhibiting Type-I photochemistry and enhancing absorption intensity in the blue to near-infrared region. Reactive oxygen species generation of metallopolymer Ir-P1, where the iridium atom is covalently coupled to the polymer backbone, is over 80 times higher than that of its mother polymer without iridium under 680 nm irradiation. This strategy also works effectively when the iridium atom is directly included (Ir-P2) in the polymer backbones, exhibiting wide generality. The metallopolymer nanoparticles exhibiting efficient O2â¢- generation are conjugated with integrin αvß3 binding cRGD to achieve targeted photodynamic therapy.
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Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/química , Iridio/química , Hipoxia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Polímeros/uso terapéutico , Microambiente TumoralRESUMEN
Nanobodies as imaging agents and drug conjugates have shown great potential for cancer diagnostics and therapeutics. However, site-specific modification of a nanobody with microbial transglutaminase (mTGase) encounters problems in protein separation and purification. Here, we describe a facile yet reliable strategy of immobilizing mTGase onto magnetic beads for site-specific nanobody modification. The mTGase immobilized on magnetic beads (MB-mTGase) exhibits catalytic activity nearly equivalent to that of the free mTGase, with good reusability and universality. Magnetic separation simplifies the protein purification step and reduces the loss of nanobody bioconjugates more effectively than size exclusion chromatography. Using MB-mTGase, we demonstrate site-specific conjugation of nanobodies with fluorescent dyes and polyethylene glycol molecules, enabling targeted immunofluorescence imaging and improved circulation dynamics and tumor accumulation in vivo. The combined advantages of MB-mTGase method, including high conjugation efficiency, quick purification, less protein loss, and recycling use, are promising for site-specific nanobody functionalization and biomedical applications.
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Anticuerpos de Dominio Único , Polietilenglicoles , Fenómenos Magnéticos , Transglutaminasas/metabolismoRESUMEN
The sorghum-sudangrass hybrid is the main high-quality forage grass in Southwest China, but, in recent years, it has suffered from leaf spot disease, with a prevalence of 88% in Bazhong, Sichuan, China, seriously affecting yield and quality. The causal agents were obtained from symptomatic leaves by tissue isolation and verified by pathogenicity assays. A combination of morphological characterization and sequence analysis revealed that strains SCBZSL1, SCBZSX5, and SCBZSW6 were Nigrospora sphaerica, Colletotrichum boninense, and Didymella corylicola, respectively, and the latter two were the first instance to be reported on sorghum-sudangrass hybrids in the world. SCBZSX5 significantly affected the growth of the plants, which can reduce plant height by 25%. The biological characteristics of SCBZSX5 were found to be less sensitive to the change in light and pH, and its most suitable culture medium was Potato Dextrose Agar (PDA), with the optimal temperature of 25 °C and lethal temperature of 35 °C. To clarify the interactions between the pathogen SCBZSX5 and plants, metabolomics analyses revealed that 211 differential metabolites were mainly enriched in amino acid metabolism and flavonoid metabolism. C. boninense disrupted the osmotic balance of the plant by decreasing the content of acetyl proline and caffeic acid in the plant, resulting in disease occurrence, whereas the sorghum-sudangrass hybrids improved tolerance and antioxidant properties through the accumulation of tyrosine, tryptophan, glutamic acid, leucine, glycitein, naringenin, and apigetrin to resist the damage caused by C. boninense. This study revealed the mutualistic relationship between sorghum-sudangrass hybrids and C. boninense, which provided a reference for the control of the disease.
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The use of bone marrow stromal cells (BMSCs) for bone defect repair has shown great promise due to their differentiation potential. However, isolating the BMSCs from various cell types within the bone marrow remains challenging. To tackle this issue, we utilized semiconducting polymer dots (Pdots) as markers to select the BMSCs within a specific time frame. The therapeutic efficacy of the obtained Pdot-labeled BMSCs was assessed in a bone defect model. Initially, we evaluated the binding capacity of the Pdots with four different types of cells present in the bone marrow including BMSCs, osteoblasts, macrophages, and vascular endothelial cells, in vitro. Notably, BMSCs showed the most rapid uptake of the Pdots, being labeled within only one h of coculture, while other cells took four h to become labeled. Moreover, by colocalizing the Pdots with Prrx1, Sca-1, OSX, F480, and CD105 in the bone marrow cells of monocortical tibial defect (MTD) mice in vivo, we determined the proportions of BMSCs, macrophages, and vascular endothelial cells among all labeled cells from 1 to 8 h after the Pdots injection. It was found that BMSCs have the highest proportion (92%) among all labeled cells extracted after 1 h of Pdots injection. The therapeutic efficacy of the obtained Pdots-labeled BMSCs (1 h) was assessed in a bone defect model. Results showed that the new bone accrual was significantly increased in the treatment of Pdots-labeled BMSCs compared to the bone marrow cell-treated group. Our study revealed that BMSCs screened by the Pdots could improve bone defect repair, suggesting a promising application of the Pdots in bone healing.
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Fluorescence imaging in the second near-infrared (NIR-II) window has attracted considerable interest in investigations of vascular structure and angiogenesis, providing valuable information for the precise diagnosis of early stage diseases. However, it remains challenging to image small blood vessels in deep tissues because of the strong photon scattering and low fluorescence brightness of the fluorophores. Here, we describe our combined efforts in both fluorescent probe design and image algorithm development for high-contrast vascular imaging in deep turbid tissues such as mouse and rat brains with intact skull. First, we use a polymer blending strategy to modulate the chain packing behavior of the large, rigid, NIR-II semiconducting polymers to produce compact and bright polymer dots (Pdots), a prerequisite for in vivo fluorescence imaging of small blood vessels. We further developed a robust Hessian matrix method to enhance the image contrast of vascular structures, particularly the small and weakly fluorescent vessels. The enhanced vascular images obtained in whole-body mouse imaging exhibit more than an order of magnitude improvement in the signal-to-background ratio (SBR) as compared to the original images. Taking advantage of the bright Pdots and Hessian matrix method, we finally performed through-skull NIR-II fluorescence imaging and obtained a high-contrast cerebral vasculature in both mouse and rat models bearing brain tumors. This study in Pdot probe development and imaging algorithm enhancement provides a promising approach for NIR-II fluorescence vascular imaging of deep turbid tissues.
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Vendajes , Imagen Óptica , Animales , Ratones , Ratas , Imagen de Cuerpo Entero , Colorantes Fluorescentes , PolímerosRESUMEN
Photothermal therapy has attracted enormous attention as an efficient treatment modality in cancer ablation but still encounters a major bottleneck due to the limited penetration depth of light inside tissues. To overcome the challenge of deep tissue penetration, we present a strategy of endovascular photothermal precision embolization (EPPE), which employs an endovascular optical fiber to induce local embolization only in the entrance of feeding vessels through photothermal heating for the purpose of fully blocking the blood supply of the whole tumor. In EPPE, we apply a highly efficient and biocompatible photothermal agent, i.e., near-infrared (NIR)-light-absorbing diketopyrrolopyrrole-dithiophene-based nanoparticle, which exhibits a high cell-killing efficacy at a concentration of 200 µg/mL using 808 nm laser irradiation of 0.5 W/cm2 within 5 min in both 2D cell culture and a 3D tumor spheroid model. We verify the feasibility of EPPE in an ex vivo organ-structured recellularized liver model and further confirm the in vivo efficacy of the photothermal treatment in a rat liver model. The photothermal treatment combined with the embolization effect holds promise to serve as an effective starvation therapy to treat tumors of varying sizes and locations.
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Hipertermia Inducida , Nanopartículas , Línea Celular Tumoral , FototerapiaRESUMEN
Photosensitizers to precise target and change fluorescence upon light illumination could accurately self-report where and when the photosensitizers work, enabling us to visualize the therapeutic process and precisely regulate treatment outcomes, which is the unremitting pursuit of precision and personalized medicine. Here, we report self-immolative photosensitizers by adopting a strategy of light-manipulated oxidative cleavage of CâC bonds that can generate a burst of reactive oxygen species, to cleave to release self-reported red-emitting products and trigger nonapoptotic cell oncosis. Strong electron-withdrawing groups are found to effectively suppress the CâC bond cleavage and phototoxicity via studying the structure-activity relationship, allowing us to elaborate NG1-NG5 that could temporarily inactivate the photosensitizer and quench the fluorescence by different glutathione (GSH)-responsive groups. Thereinto, NG2 with 2-cyano-4-nitrobenzene-1-sulfonyl group displays excellent GSH responsiveness than the other four. Surprisingly, NG2 shows better reactivity with GSH in weakly acidic condition, which inspires the application in weakly acidic tumor microenvironment where GSH elevates. To this end, we further synthesize NG-cRGD by anchoring integrin αvß3 binding cyclic pentapeptide (cRGD) for tumor targeting. In A549 xenografted tumor mice, NG-cRGD successfully deprotects to restore near-infrared fluorescence because of elevated GSH in tumor site, which is subsequently cleaved upon light irradiation releasing red-emitting products to report photosensitizer working, while effectively ablating tumors via triggered oncosis. The advanced self-immolative organic photosensitizer may accelerate the development of self-reported phototheranostics in future precision oncology.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Ratones , Animales , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Neoplasias/tratamiento farmacológico , Autoinforme , Medicina de Precisión , Glutatión/química , Línea Celular Tumoral , Nanopartículas/química , Microambiente TumoralRESUMEN
Overexpression of CD47 is frequently observed in various types of human malignancies, inhibiting myeloid-mediated elimination of tumor cells and affecting the prognosis of cancer patients. By mapping biomarker expression, immuno-positron emission tomography has been increasingly used for patient screening and response monitoring. By immunization alpacas with recombinant human CD47, we prepared a CD47-targeting nanobody C2 and developed [68Ga]Ga-NOTA-C2, followed by an exploration of the diagnostic value in CD47-expressing tumor models including gastric-cancer patient-derived xenograft models. By fusing C2 to an albumin binding domain (ABD), we synthesized ABDC2, which had increased in vivo half-life and improved targeting properties. We further labeled ABDC2 with 68Ga/89Zr/177Lu to develop radionuclide theranostic pairs and evaluated the pharmacokinetics and theranostic efficacies of the agents in cell- and patient-derived models. Both C2 and ABDC2 specifically reacted with human CD47 with a high K D value of 23.50 and 84.57 pM, respectively. [68Ga]Ga-NOTA-C2 was developed with high radiochemical purity (99 >%, n = 4) and visualized CD47 expression in the tumors. In comparison to the rapid renal clearance and short half-life of [68Ga]Ga-NOTA-C2, both [68Ga]Ga-NOTA-ABDC2 and [89Zr]Zr-DFO-ABDC2 showed prolonged circulation and increased tumor uptake, with the highest uptake of [89Zr]Zr-DFO-ABDC2 occurring at 72 h post-injection. Moreover, [177Lu]Lu-DOTA-ABDC2 radioimmunotherapy suppressed the tumor growth but was associated with toxicity, warranting further optimization of the treatment schedules. Taken together, we reported a series of nanobody-derived CD47-targeted agents, of which [68Ga]Ga-NOTA-C2 and [89Zr]Zr-DFO-ABDC2 are readily translatable. Optimization and translation of CD47-targeted theranostic pair may provide new prospects for CD47-targeted management of solid tumors.
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Two photoswitchable semiconducting polymers were synthesized by covalently incorporating photochromic dithienylethene (DTE) into the main chains. Small size polymer dots (Pdots) were prepared and showed dynamic photoswitching upon alternate light irradiation. By virtue of the tunable photoswitching properties, effective pattern encoding and superresolution imaging with a resolution of up to about 30 nm were achieved.
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Mesenchymal stem cell-derived exosomes (MSC-Exos) are emerging as a promising platform for treating various intractable diseases and organ injuries. Monitoring their migration, homing, and therapeutic capability in vivo is essential to develop exosome-based theranostics. Here, we designed fluorescent semiconductor polymer dots (Pdots) in the second near-infrared window (NIR-II) for bright labeling and tracking of MSC-Exos. Glucose-coated Pdots (Pdots-Glu) were able to label MSC-Exos without changing their biological properties. The NIR-II fluorescent Pdots allow for high labeling brightness and long-term in vivo tracking of MSC-Exos. We investigated the biodistributions and therapeutic functions of these labeled MSC-Exos in liver-resected mice. In vivo and ex vivo imaging demonstrated that the Pdot-labeled MSC-Exos injected via the tail vein mainly accumulated in the residual liver tissue. In terms of the therapeutic effect, MSC-Exos may accelerate postoperative liver function recovery by inhibiting inflammatory responses, promoting cell proliferation, and resisting apoptosis. Our results indicated that MSC-Exos therapeutic systems hold promising applications in liver regenerative medicine.
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Exosomas , Células Madre Mesenquimatosas , Ratones , Animales , Polímeros , Hígado , Proliferación Celular/fisiologíaRESUMEN
Aberrant cerebral glucose metabolism is related to many brain diseases, especially brain tumor. However, it remains challenging to measure the dynamic changes in cerebral glucose. Here, we developed a near-infrared (NIR) optical transducer to sensitively monitor the glucose variations in cerebrospinal fluid in vivo. The transducer consists of an oxygen-sensitive nanoparticle combined with glucose oxidase (GOx), yielding highly sensitive NIR phosphorescence in response to blood glucose change. We demonstrated long-term continuous glucose monitoring by using the NIR transducer. After subcutaneous implantation, the glucose transducer provides a strong luminescence signal that can continuously monitor blood glucose fluctuations for weeks. By using the NIR emission of the transducer, we further observed abnormal dynamic changes in cerebrospinal fluid glucose and quantitatively assessed cerebral glucose uptake rates in transgenic mice bearing brain tumors. This study provides a promising method for the diagnosis of various metabolic diseases with altered glucose metabolism.
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Neoplasias Encefálicas , Glucosa , Animales , Glucemia , Automonitorización de la Glucosa Sanguínea , Neoplasias Encefálicas/diagnóstico por imagen , Glucosa Oxidasa , Ratones , Imagen Óptica , Oxígeno , Espectroscopía Infrarroja Corta/métodos , TransductoresRESUMEN
Glioma with very short medium survival time consists of 80% of primary malignant types of brain tumors. The unique microenvironment such as the existence of the blood-brain barrier (BBB) makes the glioma theranostics exhibit low sensitivity in diagnosis, a poor prognosis and low treatment efficacy. Therefore, the development of multifunctional nanoplatform that can cross BBB and target the glioma is essential for the high-sensitivity detection and ablation of cancer cells. In this study, C6 cell membrane-coated conjugated polymer dots (Pdots-C6) were constructed for targeted glioma tumor detection. As a new kind of biomimetic and biocompatible nanoprobes, Pdots-C6 preserve the complex biological functions of natural cell membranes while possessing physicochemical properties for NIR-II fluorescence imaging of glioma. After encapsulating C6 cell membrane on the surface of conjugated Pdots, Pdots-C6 exhibited the most favorable specific targeting capabilities in vitro and in vivo. In particular, this pilot study demonstrates that biomimetic nanoparticles offer a potential tool to enhance specific targeting to the brain, hence improving glioma tumor detection accuracy.
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Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds great potential for the accurate visualization of deeply located biological structures in vivo. However, the weak fluorescence of current NIR-II fluorophores remains a long-standing challenge for the ever-growing imaging demand. Here, we describe a surface plasmon-enhanced NIR-II fluorescence strategy by incorporating silica-coated gold nanorods (GNRs) and polymer dots (Pdots) into a multilayer nanostructure. Precise manipulation of the silica spacing layer thickness signifies an optimum distance of 8.6 nm, where an enhancement factor of up to 6.4 is achieved in the NIR-II imaging window. The surface plasmon enhancement approach is successfully extended to several types of Pdots fluorophores with NIR-II emission. We finally perform outer-layer encapsulation and PEGylation for the multilayer probes and demonstrate surface plasmon-enhanced NIR-II fluorescence for mouse brain imaging through the skull, which exhibits a refined signal-to-background ratio and penetration depth as compared to the clinically approved ICG dye.
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Colorantes Fluorescentes , Imagen Óptica , Animales , Colorantes Fluorescentes/química , Ratones , Neuroimagen , Imagen Óptica/métodos , Polímeros , Dióxido de Silicio/química , CráneoRESUMEN
Ginkgo (Ginkgo biloba L.) is a tree valued for the high medicinal and nutritional value of its leaves and seeds. However, the metabolite profiles of ginkgo leaves and seeds and their changes during development have not been comprehensively analyzed, which hinders improvements in the utilization of ginkgo. A comprehensive and systematic untargeted LC-MS metabolomics analysis of the metabolites in ginkgo leaves (male and female) and seeds at two developmental stages identified 8146 known metabolites, which mainly included lipids and lipid-like molecules, phenylpropanoids and polyketides, organoheterocyclic compounds, organic acids and derivatives, organic oxygen compounds, and benzenoids. Some of the identified metabolites have known healthcare and food value, and some of the others are newly discovered metabolites with potential for new drug development. The small number of differential Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between leaves of male and female gingko trees indicated that the developmental stage affected the metabolic pathways more significantly than sex. Among the flavonoid constituents of ginkgo, 653 flavonoid metabolites were identified, and these included some new flavonoid components, which confirmed that the developmental stage is a critical factor in secondary metabolite variations. This study illuminated the metabolites and medicinal and edible values of ginkgo leaves and seeds at different developmental stages and thus supports further effective utilization of ginkgo leaves and seeds.
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Ginkgo biloba , Espectrometría de Masas en Tándem , Cromatografía Liquida , Flavonoides/metabolismo , Ginkgo biloba/metabolismo , MetabolómicaRESUMEN
Here, we confined fluorescent probes to solid nanochannels to construct nanosensors, which not only significantly improved the reusability of the molecular probes, but also achieved ion current and fluorescence dual gating for more reliable detection. The combination of optical and electrical modalities can provide comprehensive spatiotemporal information that can be used to elucidate the sensing mechanism within the nanochannel. As a proof-of-concept experiment, fluorescein isothiocyanate (FITC)−hydrazine (N2H4) was selected to modify nanochannels for the effective detection of Hg2+. Based on spirolactam opening tactics, the system synergistically alters the surface charge and fluorescence intensity in response to Hg2+, establishing a dual open state of current and fluorescence. The newly prepared nanosensor exhibited a fast response (<1 min), high sensitivity, and selectivity towards Hg2+. Importantly, the nanodevice could be recovered by simple N2H4 treatment. Such sensing behavior could be used to implement optoelectronic dual-output XOR logical gates under the management of Hg2+ and N2H4. This strategy is anticipated to find broad applications in other nanochannel-based systems for various sensing applications used for monitoring of pollutants, food additives, and biomolecules.
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Optical sensors have attracted a great deal of interest for glucose detection. However, their practical applications for continuous glucose monitoring are still constrained by operational reliability in subcutaneous tissues. Here, we show an implantable hydrogel platform embedded with luminescent polymer dots (Pdots) for sensitive and long-term glucose monitoring. We use Pdot transducer in a polyacrylamide hydrogel matrix to construct an implantable platform. The hydrogel-Pdot transducer showed bright luminescence with ratiometric response to glucose changes. The in vitro and in vivo sensitivities of the hydrogel implant were enhanced by varying the enzyme concentration and injection volume. After implantation, the hydrogel with Pdot transducer remained at the implanted site without migration for 1 month and can be removed from the subcutaneous tissue for further analysis. Our results indicate that the hydrogel-Pdot platform maintains the intrinsic sensing property with excellent stability during 1 month implantation, while fibrous capsule formation on the implant in some cases needs to be solved for long-term continuous glucose monitoring.