Small molecular fluorophores in the second near-infrared window (NIR-II) have aroused much interest because of their excellent performance. Herein, a new small molecular NIR-II fluorophore, FM1210, with maximal emission beyond 1200 nm is reported. Compared to the corresponding control fluorophore CF1065, FM1210 exhibits an increase of 145 nm in the emission maximum, which is ascribed to the simultaneous introduction of both a Se atom and amino groups into the benzo[1,2-c:4,5-c′]bis([1,2,5]thiadiazole) skeleton. This large increase in the maximal emission enables FM1210 to be capable of in vivo imaging with lower autofluorescence, higher signal-to-background ratio, and better resolution. Moreover, nanosized FM1210 encapsulated in liposomes possesses passive targeting ability and good water solubility, and is suitable for imaging a tumor and even its vasculature with high signal-to-background ratio.
The accurate discrimination of microRNAs (miRNAs) with highly similar sequences would greatly facilitate the screening and early diagnosis of diseases. In the present work, a locked nucleic acid (LNA)-modified probe was designed and used for α-hemolysin (α-HL) nanopore to selectively and specifically identify miRNAs. The hybridization of the LNA probe with the target miRNAs generated unique long-lived signals in the nanopore thus facilitated an accurate discrimination of miRNAs with similar sequences, even a single-nucleotide difference. Furthermore, the developed nanopore-based analysis with LNA probe could selectively detect target miRNAs in a natural serum background. This selective and sensitive approach may be highly valuable in the detection of clinically relevant biomarkers in complex samples.
Human 8-oxoguanine DNA glycosylase (hOGG1) plays a significant role in maintaining the genomic integrity of living organisms for its capability of repairing DNA lesions. Accurate detection of hOGG1 activity would greatly facilitate the screening and early diagnosis of diseases. In this work, we report a nanopore-based sensing strategy to probe the hOGG1 activity by employing the enzyme-catalytic cleavage reaction of DNA substrate. The hOGG1 specifically catalyzed the removal of the 8-hydroxyguanine (8-oxoG) and cleaved the DNA substrates immobilized on magnetic beads, thereby releasing the output DNA which would quantitatively produce the signature current events when subjected to α-hemolysin (α-HL) nanopore test. The approach enables the sensitive detection of hOGG1 activity without the need of any labeling or signal amplification route. Furthermore, the method can be applied to assay the inhibition of hOGG1 and evaluate the activity of endogenous hOGG1 in crude cell extracts. Importantly, since DNAs with specific sequences are the catalytic substrates of a wide variety of enzymes, the proposed strategy should be universally applicable for probing the activities of different types of enzymes with nanopore sensors.
Acetylcholinesterase (AChE) is an extremely critical hydrolase tightly associated with neurological diseases. Currently, specific substrates available for imaging AChE activity still remain a great challenge due to the interference from...
Monoamine
oxidase (MAO) has two isomers (A and B), and the analysis
of each one in biological samples is of great potential in studying
MAO-related diseases. However, specific detection and imaging of MAO-A
in cells and in vivo are still a great challenge
at present due to the relative lack of suitable near-infrared (NIR)
fluorescent probes. In this work, two new NIR fluorescent probes,
Rma-1 and Rma-2, have been developed for the analysis of MAO-A in
living biosystems. The probes were designed by conjugating the specific
structure of the MAO-A inhibitor to hemicyanine (an NIR fluorophore)
directly or through a self-immolative linker. Both probes are water-soluble
and showed selective and sensitive NIR (708 nm) responses toward MAO-A
rather than MAO-B, of which probe Rma-1 with a self-immolative linker
exhibited superior analytical performance with a detection limit of
4.5 ng/mL and 13-fold specificity for MAO-A over MAO-B. Further, probe
Rma-1 has been successfully utilized to image the MAO-A activity in
cells, zebrafish, and tumor-bearing mice, showing a promising prospect
for MAO-A study in carcinoma.
Many fluorophores/probes suffer from the interference of albumin in biosystems. Herein, we propose an effective strategy to overcome this interference by virtue of both an albumin‐insensitive fluorophore and its changeable π‐conjugation, and demonstrate the strategy by designing an oxazine‐based fluorogenic probe for aminopeptidase N (APN). The modification on the N atom in the oxazine fluorophore with alanine through a cleavable linker locks the resulting probe in a non‐conjugated, colorless and non‐fluorescent state, so the non‐specific interaction of albumin produces no spectroscopic response. APN can selectively cleave the alanine moiety, restoring the large π‐conjugation and strong fluorescence. The capability of the probe to eliminate the albumin influence has been demonstrated by imaging APN in different cell lines, and by quantitatively determining APN in human serum and mouse urine. The present strategy may be useful for developing more specific fluorogenic probes for other enzymes.
A fluorimetric Hg2+ test strip has been developed using a lotus-inspired fabrication method for suppressing the “coffee stains” toward the uniform distribution of probe materials through creating a hydrophobic drying pattern for fast solvent evaporation. The test strips were first loaded with the model probes of fluorescent gold-silver nanoclusters and then dried in vacuum on the hydrophobic pattern. On the one hand, here, the hydrophobic constraining forces from the lotus surface-like pattern could control the exterior transport of dispersed nanoclusters on strips leading to the minimized “coffee stains”. On the other hand, the vacuum-aided fast solvent evaporation could boost the interior Marangoni flow of probe materials on strips to expect the further improved probe distribution on strips. High aqueous stability and enhanced fluorescence of probes on test strips were realized by the hydrophilic treatment with amine-derivatized silicane. A test strips-based fluorimetry has thereby been developed for probing Hg2+ ions in wastewater, showing the detection performances comparable to the classic instrumental analysis ones. Such a facile and efficient fabrication route for the bio-inspired suppression of “coffee stains” on test strips may expand the scope of applications of test strips-based “point-of-care” analysis methods or detection devices in the biomedical and environmental fields.
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