Al-Based Metal-Organic Nanoslice-Coupled Phospholipid Layer Enables Highly Enriched Biological External Vesicles.

Systematic analysis of the information content of biological external vesicles (BEVs) is essential for understanding the complex relationships between metabolic processes and cells at a systemic level. Although considerable efforts have been made to enrich BEVs, their comprehensive analysis in a way that maintains and stabilizes information maintenance at high doses remains a challenge. To address this issue, we developed a metal-organic nanoslice-coupled exocytosis phospholipid layer method that utilized subtle interactions between the metal-organic nanoslice and the phospholipid molecular layer of the membrane to achieve the convenient and efficient enrichment of BEVs.

A shikimic acid derived carbon dots (SACNDs-FITC) for multi-modal detection and removal of Hg: Probe design, sensing performance, and applications in food analysis.

The first shikimic acid derived fluorescent carbon dots (SACNDs-FITC) for multi-modal detection and simultaneous removal of Hg is revealed. The fluorescence of SACNDs-FITC centered at 520 nm can be selectively quenched by Hg, while the emission centered at 420 nm remains constant which can be used for self-calibration. Naked-eye distinguishable color change from yellow to colourless under daylight and from green to blue under UV light could be observed for SACNDs-FITC in the real-time detection of Hg.

Ice-pop making inspired photothermal ultra-swelling microneedles to facilitate loading and intradermal vaccination of tumor antigen.

Cancer vaccines hold great promise in the fight against cancer. Here, we report an ice-pop making inspired photothermal ultra-swelling microneedle (PUSMN) patch for facilitating and enhancing cancer vaccination. The PUSMN patch consist of an array of microneedles made from photo-crosslinked methacrylated hyaluronic acid and polydopamine, a near-infrared photothermal conversion material, connected to a customized resin handle like an ice-pop stick.

Bimodal accurate HO regulation to equalize tumor-associated macrophage repolarization and immunogenic tumor cell death elicitation.

Simultaneous implementation of tumor-associated macrophage (TAM) repolarization and immunogenic tumor cell death (ICD) elicitation enables tumor immunotherapy with high efficacy. However, the inconsistency of stimulation tolerance restricts simultaneous implementation. To address this obstacle, we validate that an HO-mediated regulatory strategy could achieve coordinated occurrences.

Functional Metallocenes as Cofactors Promote the Catalytic Performance of Mimetic Enzymes.

Coenzymes (cofactors) are essential for bio-redox reactions, group transfer reactions, and heterogeneous reactions of bio-enzymes, as well as the auxiliary transfer of electrons or atoms to promote bio-enzyme activity. However, when mimetic enzymes are scaled to the micro or nanoscale levels, both the absence of cofactor activity and the presence of migrating internal atoms cause self-depletion, eventually limiting sustained usage. Herein, cofactor regulation, a key issue long neglected in traditional mimetic enzyme construction is addressed.

FRET-Based Dual-Color Carbon Dot Ratiometric Fluorescent Sensor Enables the Smartphone-Integrated Device for Noninvasive and Portable Diagnosis of Chronic Kidney Disease.

Cystatin C (Cys C), a crucial renal disease marker for chronic kidney disease (CKD), plays a vital role in early diagnosis and treatment guidance. However, most current methods for detecting Cys C rely on a single signal and find it difficult to perform noninvasive and portable diagnosis. Here, we developed a ratiometric fluorescent carbon dot (CD) detection system for point-of-care testing (POCT) of Cys C through fluorescence resonance energy transfer (FRET).

Tetraalkynylporphyrin-mediated covalent assembly of gold nanoclusters for targeted tumor fluorescence imaging and enhanced photodynamic therapy.

A covalent assembly strategy was developed to construct a gold nanocluster-based nano-assembly (AuNCNA) in a controllable manner, using Au nanocluster as node and 5,10,15,20-tetra(4-alkynylphenyl)porphine (TEPP) as ligand. Subsequently, the tripeptide arginine glycine aspartic acid (RGD) peptide is further modified via clicking reaction to build a multi-functional nanoplatform (AuNCNA@RGD) that can integrate the targeted fluorescence imaging and efficient photodynamic therapy (PDT). The strong interregulation of Au nanocluster and TEPP results in AuNCNA@RGD exhibiting three distinct advantages: (i) TEPP plays an important role in stabilizing the Au nanocluster and keeping the active site fixed within the framework, thereby enhancing stability of Au nanocluster; (ii) Au nanocluster possess adjustable energy level, which can accelerate the transfer of photogenerated charge and prevent the recombination of electrons and holes, thus improving the photosensitivity of TEPP for PDT; (iii) AuNCNA exhibits bright fluorescence emission that facilitates RGD-assisted targeted tumor imaging.

Valence-Transforming O-Depleting Nano-Assembly Enable In Situ Tumor Depositional Embolization.

Abnormal metabolism and blood supply/O imbalance in tumor cells affect drug transport delivery and increase the difficulty of tumor treatment. Controlling tumor growth by inhibiting tumor cell metabolism and regulating progressive embolization in the tumor region provides an innovative basis for constructing tumor therapeutic models. A highly biocompatible and efficient O-depleting agent has been investigated to enable in situ precipitation and embolization within the tumor microenvironment.

Dimensional regulation of lanthanide metal-organic frameworks and their application in bacterial detection.

Low-dimensional (LD) lanthanide metal-organic frameworks (Ln-MOFs) have attracted considerable attention in different fields due to their exceptional optical properties and numerous accessible active sites. Through the dimensional regulation effect of dipicolinic acid (DPA), a new LD Ln-MOF crystal is synthesized to monitor nitroreductase (NTR) activity in living bacteria.

Development of Integrin-Facilitated Bispecific Aptamer Chimeras for Membrane Protein Degradation.

The emergence of lysosome-targeting chimeras (LYTACs), which represents a promising strategy for membrane protein degradation based on lysosomal pathways, has attracted much attention in disease intervention and treatment. However, the expression level of commonly used lysosome-targeting receptors (LTRs) varies in different cell lines, thus limiting the broad applications of LYTACs. To overcome this difficulty, we herein report the development of integrin α3β1 (ITGA3B1)-facilitated bispecific aptamer chimeras (ITGBACs) as a platform for the degradation of membrane proteins.

Highly efficient removal and real-time visual detection of fluoride ions using ratiometric CAU-10-NH@RhB: Probe design, sensing performance, and practical applications.

The extensive use of fluoride in agriculture, industry, medicine, and daily necessities has raised growing concerns about fluoride residue. To date, real-time visual detection and efficient removal of fluoride ions from water remain greatly desirable. Herein, nano-CAU-10-NH@RhB is introduced as a ratiometric fluorescent probe and efficient scavenger for the intelligent detection and removal of fluoride ions.

Regulating Arrhenius Activation Energy and Fluorescence Quantum Yields of AuNCs-MOF to Achieve High Temperature Sensitivity in a Wide Response Window.

Luminescent thermometry affords remote measurement of temperature and shows huge potential in future technology beyond those possible with traditional methods. Strategies of temperature measurement aiming to increase thermal sensitivity in a wide temperature response window would represent a pivotal step forward, but most thermometers cannot do both of them. Herein, we propose a balancing strategy to achieve a trade-off between high Arrhenius activation energy (), which could stretch the temperature response windows, and fluorescence quantum yields (QYs) in a manner that will increase thermal sensitivity in a wide response window.

Twisted Intramolecular Charge Transfer-Based Viscosity-Responsive Probe Reveals Lysosomal Degradation Process of Endocytosed Foreign Bodies.

The optimization of nanomedicines requires a thorough understanding of nanocarrier attrition during lysosome-mediated biological processes. Real-time monitoring of endocytosis provides valuable insights into the lysosomal effects on nanocarriers and the release of nanodrugs. We report the development of a coresponsive probe that detects changes in the spatial viscosity of the intracellular domain caused by lysosomal degradation of foreign bodies.

Integrating a Copper-Histidine Brace in a Mimetic Nanozyme Streamlines the Tyrosinase Recognition Moiety to Achieve Chiral Differentiation.

Designing artificial mimetic enzymes with high activity/selectivity to replace chiral bioenzymes is of great interest in the development of chiral materials consisting of molecules, enantiomers, that exist in two forms as mirror images of one another but cannot be superimposed. In this study, the chiral catalytic structural unit was streamlined from tyrosinase to integrate a mimetic nanozyme. The chiral amino acid l-histidine, as the chiral binding/recognition site, and the active metal site Cu were coupled (Cu@l-His) to create a copper-histidine brace with enantioselective catalytic ability to tyrosinol enantiomers.

Fabrication and Characterization of Microneedle Patches for Loading and Delivery of Exosomes.

Exosomes, as emerging "next-generation" biotherapeutics and drug delivery vectors, hold immense potential in diverse biomedical fields, ranging from drug delivery and regenerative medicine to disease diagnosis and tumor immunotherapy. However, the rapid clearance by traditional bolus injection and poor stability of exosomes restrict their clinical application. Microneedles serve as a solution that prolongs the residence time of exosomes at the administration site, thereby maintaining the drug concentration and facilitating sustained therapeutic effects.

Empowering Exosomes with Aptamers for Precision Theranostics.

As information messengers for cell-to-cell communication, exosomes, typically small membrane vesicles (30-150 nm), play an imperative role in the physiological and pathological processes of living systems. Accumulating studies have demonstrated that exosomes are potential biological candidates for theranostics, including liquid biopsy-based diagnosis and drug delivery. However, their clinical applications are hindered by several issues, especially their unspecific detection and insufficient targeting ability.

Fabrication of a two-dimensional bi-lanthanide metal-organic framework as a ratiometric fluorescent sensor based on energy competition.

Bimetallic lanthanide metal-organic frameworks (bi-Ln-MOFs) exhibit great appeal for ratiometric luminescent sensors due to their unique advantages. Specially, the low-lying energy of the empty 4f band of Ce ions benefits Ce-MOFs with robust and broad fluorescent emission. Therefore, constructing ratiometric sensors based on Ce-MOFs is of significance but remains a challenge.

Dual-Aptamer Recognition of DNA Logic Gate Sensor-Based Specific Exosomal Proteins for Ovarian Cancer Diagnosis.

Clinical diagnosis of ovarian cancer lacks high accuracy due to the weak selection of specific biomarkers along with the circumstance biomarkers localization. Clustering analysis of proteins transported on exosomes enables a more precise screening of effective biomarkers. Herein, through bioinformatics analysis of ovarian cancer and exosome proteomes, two coexpressed proteins, EpCAM and CD24, specifically enriched, were identified, together with the development of an as-derived dual-aptamer targeted exosome-based strategy for ovarian cancer screening.

Rapid Correction of the Hypoglycemia State in Nonhuman Primates Using a Glucagon Long-Dissolving Microneedle Patch.

The timely administration of glucagon is a standard clinical practice for the treatment of severe hypoglycemia. However, the process involves cumbersome steps, including the reconstitution of labile glucagon and filling of the syringe, which cause considerable delays in emergency situations. Moreover, multiple dosages are often required to prevent the recurrence of the hypoglycemic episode because of the short half-life of glucagon in plasma.

Metal-organic framework-based ratiometric point-of-care testing for quantitative visual detection of nitrite.

Nitrite (NO) is categorized as a carcinogenic substance and is subjected to severe limitations in water and food. To safeguard the public's health, developing fast and convenient methods for determination of NO is of significance. Point-of-care testing (POCT) affords demotic measurement of NO and shows huge potential in future technology beyond those possible with traditional methods.

An ATMND/SGI based three-way junction ratiometric fluorescent probe for rapid and sensitive detection of bleomycin.

In this work, we developed a rapid and sensitive label-free ratiometric fluorescent (FL) probe for the detection of bleomycin (BLM). The probe consists of a DNA sequence (D6) and two fluorophore groups, 2-amino-5,6,7-trimethyl-1,8-naphthalene (ATMND) and SYBR Green I (SGI). The D6 sequence could be folded into a three-way junction structure containing a C-C mismatch position in the junction pocket.

An Aptamer-Based Nanoflow Cytometry Method for the Molecular Detection and Classification of Ovarian Cancers through Profiling of Tumor Markers on Small Extracellular Vesicles.

Molecular profiling of protein markers on small extracellular vesicles (sEVs) is a promising strategy for the precise detection and classification of ovarian cancers. However, this strategy is challenging owing to the lack of simple and practical detection methods. In this work, using an aptamer-based nanoflow cytometry (nFCM) detection strategy, a simple and rapid method for the molecular profiling of multiple protein markers on sEVs was developed.

Ratiometric fluorescence determination of alkaline phosphatase activity based on carbon dots and Ce-crosslinked copper nanoclusters.

A new ratiometric fluorescent probe for efficient determination of ALP was developed. The probe was constructed by combining Ce-crosslinked copper nanoclusters (Ce-CuNCs) which exhibit the aggregation-induced emission (AIE) feature with carbon dots (CDs). The introduction of phosphate (Pi) induced the generation of CePO precipitation, resulting in significant decrease of fluorescence emission of CuNCs at 634 nm.