To facilitate on-site detection by nonspecialists, there is a demand for the development of portable "sample-to-answer" devices capable of executing all procedures in an automated or easy-to-operate manner. Here, we developed an automated detection device that integrated a magnetofluidic manipulation system and a signal acquisition system. Both systems were controllable via a smartphone.
View Article and Find Full Text PDFDue to the inherent immunosuppression and immune evasion of cancer cells, combining photoimmunotherapy with immune checkpoint blockade leverages phototherapy and immune enhancement, overcoming mutual limitations and demonstrating significant anticancer potential. The main challenges include nonspecific accumulation of agents, uncontrolled activation, and drug carrier safety. Smart DNA nanospheres (NS) is developed with targeted delivery and controllable release of photosensitizers and immune agents to achieve effective synergistic therapy and minimize side effects.
View Article and Find Full Text PDFFluctuations in cortisol levels from stressors are critical for the evaluation of endocrine function in body, and abnormal levels of cortisol may indicate serious health risks. Common strategies for cortisol detection are limited by the drawbacks of the intricate and time-consuming operations and the generation of body trauma. Herein, an aptamer-responsive microneedle patch sensor combining with hybridization chain reaction (HCR) amplification (Apt-HCR MN COR patch) was prepared for easy, accurate and minimally-invasive detection of cortisol in skin interstitial fluid (ISF).
View Article and Find Full Text PDFDetection of slight pH changes in skin interstitial fluid (ISF) is crucial yet challenging for studying pathological processes and understanding personal health conditions. In this work, we construct an i-motif DNA based fluorescent ratiometric microneedle sensing patch (IFR-pH MN patch) strategy that enables minimally invasive, high-resolution, and sensitive transdermal monitoring of small pH variations in ISF. The IFR-pH MN patch with advanced integration of both ISF sampling and pH sensing was fabricated from the cross-linking of gelatin methacryloyl and methacrylated hyaluronic acid, wrapping with pH-sensitive hairpin-containing i-motif DNA based fluorescent ratiometric probes in the matrix.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
The design and synthesis of nanomedicines capable of regulating programmed cell death patterns to enhance antitumor efficacy remain significant challenges in cancer therapy. In this study, we developed intelligent DNA nanospheres (NS) capable of distinguishing tiny pH changes between different endosomal compartments to regulate pyroptosis or apoptosis. These NS are self-assembled from two multifunctional DNA modules, enabling tumor targeting, acid-responsive disassembly, and photodynamic therapy (PDT) activation.
View Article and Find Full Text PDFPoint-of-care testing of multiple chronic disease biomarkers is crucial for timely intervention and management of chronic diseases. Here, a "sample-to-answer" microfluidic chip was developed for simultaneous detection of multiple chronic disease biomarkers in whole blood by integrating a plasma separation module. The whole detection process is very convenient, i.
View Article and Find Full Text PDFOverexpression of receptor tyrosine kinases (RTKs) or binding to ligands can lead to the formation of specific unliganded and liganded RTK dimers, and these two RTK dimers are potential targets for preventing tumor metastasis. Traditional RTK dimer inhibitor analysis was mostly based on end point assays, which required cumbersome cell handling and behavior monitoring. There are still challenges in developing intuitive process-based analytical methods to study RTK dimer inhibitors, especially those used to visually distinguish between unliganded and liganded RTK dimer inhibitors.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2024
Multidrug resistance (MDR) is a major factor in the failure of many forms of tumor chemotherapy. Development of a specific ligand for MDR-reversal would enhance the intracellular accumulation of therapeutic agents and effectively improve the tumor treatments. Here, an aptamer was screened against a doxorubicin (DOX)-resistant human hepatocellular carcinoma cell line (HepG2/DOX) via cell-based systematic evolution of ligands by exponential enrichment.
View Article and Find Full Text PDFWearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g.
View Article and Find Full Text PDFA simple and wash-free POCT platform based on microcapillary was developed, using breast cancer cell-derived exosomes as a model. This method adopted the "one suction and one extrusion" mode. The hybridized complex of epithelial cell adhesion molecule (EpCAM) aptamer and complementary DNA-horseradish peroxidase conjugate (CDNA-HRP) was pre-modified on the microcapillary's inner surface.
View Article and Find Full Text PDFUsually, different assays and instrumentation are required for different types of targets, e.g., nucleic acids, proteins, small molecules, etc.
View Article and Find Full Text PDFThe ability to reproduce signal transduction and cellular communication in artificial cell systems is significant in synthetic protobiology. Here, we describe an artificial transmembrane signal transduction through low pH-mediated formation of the i-motif and dimerization of DNA-based artificial membrane receptors, which is coupled to the occurrence of fluorescence resonance energy transfer and the activation of G-quadruplex/hemin-mediated fluorescence amplification inside giant unilamellar vesicles. Moreover, an intercellular signal communication model is established when the extravesicular H input is replaced by coacervate microdroplets, which activate the dimerization of the artificial receptors, and subsequent fluorescence production or polymerization in giant unilamellar vesicles.
View Article and Find Full Text PDFExosomes, as a non-invasive biomarker, perform an important role in breast cancer screening and prognosis monitoring. However, establishing a simple, sensitive, and reliable exosome analysis technique remains challenging. Herein, a one-step multiplex analysis electrochemical aptasensor based on a multi-probe recognition strategy was constructed to analyze breast cancer exosomes.
View Article and Find Full Text PDFMonitoring the dimerization state of the mesenchymal-epithelial transition factor (Met) was essential for in-depth understanding of the tumor signal transduction network. At present, the dimerization activation pathway of Met protein was mainly studied at the macro level, while the research at the single molecule level was far from comprehensive. Herein, the dimerization activation of Met protein's extracellular domain induced by ligand hepatocyte growth factor (HGF) was dynamically studied by single-molecule force spectroscopy.
View Article and Find Full Text PDFA portable method for on-site detection of three mycotoxins was developed based on a sonic toothbrush, microfluidic chip and smartphone. Our method could complete all procedures, including sample pretreatment, signal conversion and processing, without any sophisticated instruments. The limits of detection for these mycotoxins were lower than the limit values in cereals in the standards of China and the European Union.
View Article and Find Full Text PDFCombined detection of multiple markers related to the same disease could improve the accuracy of disease diagnosis. However, the abundance levels of multiple markers of the same disease varied widely in real samples, making it difficult for the traditional detection method to meet the requirements of a wide detection range. Herein, three kinds of cardiac biomarkers, cardiac troponin I (cTnI), myoglobin (Myo), and C-reaction protein (CRP), which were from the pM level to the μM level in real samples, were selected as model targets.
View Article and Find Full Text PDFApproaches for treating posterolateral tibial plateau fractures vary among surgeons, and the inverted L-shaped approach is a known option. This article aims to introduce a new modified posterolateral inverted L-shaped approach for isolated posterolateral tibial plateau fractures and study its feasibility. Medical records of patients with posterolateral tibial plateau fractures were reviewed.
View Article and Find Full Text PDFVisualizing intracellular microRNA (miRNA) is of great importance for revealing its roles in the development of disease. However, cell membrane barrier, complex intracellular environment and low abundance of target miRNA are three main challenges for efficient imaging of intracellular miRNA. Here, we report a size-controllable and self-assembled DNA nanosphere with ATP-fueled dissociation property for amplified miRNA imaging in live cells and mice.
View Article and Find Full Text PDFCoacervate microdroplets, formed liquid-liquid phase separation, have been proposed as a compartment model for the construction of artificial cells or organelles. However, these microsystems are very fragile and demonstrate liquid-like fluidity. Here, an artificial cytoskeleton based on DNA nanotubes was constructed in coacervate microdroplets to modulate the liquid fluidic properties of the microdroplets.
View Article and Find Full Text PDFThe design and construction of synthetic prototissues from integrated assemblies of artificial protocells is an important challenge for synthetic biology and bioengineering. Here we spatially segregate chemically communicating populations of enzyme-decorated phospholipid-enveloped polymer/DNA coacervate protocells in hydrogel modules to construct a tubular prototissue-like vessel capable of modulating the output of bioactive nitric oxide (NO). By decorating the protocells with glucose oxidase, horseradish peroxidase or catalase and arranging different modules concentrically, a glucose/hydroxyurea dual input leads to logic-gate signal processing under reaction-diffusion conditions, which results in a distinct NO output in the internal lumen of the model prototissue.
View Article and Find Full Text PDFGold nanoparticles (Au NPs) has been widely used to develop label-free colorimetric biosensors. Since the lyophilization process of Au NPs might cause various stresses and lead to irreversible aggregation, Au NPs were usually preserved in an aqueous suspension, which was inconvenienced for transportation and storage. In addition, the potential adsorption interaction between target and Au NPs was often ignored, which may lead to false-signal for Au NPs based colorimetric strategy.
View Article and Find Full Text PDFThere is considerable interest in creating a precise and sensitive strategy for in situ visualizing and profiling intracellular miRNA. Present here is a novel photocaged amplified FRET nanoflare (PAFN), which spatiotemporal controls of mRNA-powered nanomachine for precise and sensitive miRNA imaging in live cells. The PAFN could be activated remotely by light, be triggered by specific low-abundance miRNA and fueled by high-abundance mRNA.
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