Precise Capture and Dynamic Release of Circulating Liver Cancer Cells with Dual-Histidine-Based Cell Imprinted Hydrogels.

Circulating tumor cells (CTCs) detection presents significant advantages in diagnosing liver cancer due to its noninvasiveness, real-time monitoring, and dynamic tracking. However, the clinical application of CTCs-based diagnosis is largely limited by the challenges of capturing low-abundance CTCs within a complex blood environment while ensuring them alive. Here, an ultrastrong ligand, l-histidine-l-histidine (HH), specifically targeting sialylated glycans on the surface of CTCs, is designed. Furthermore, HH is integrated into a cell-imprinted polymer, constructing a hydrogel with precise CTCs imprinting, high elasticity, satisfactory blood compatibility, and robust anti-interference capacities. These features endow the hydrogel with excellent capture efficiency (>95%) for CTCs in peripheral blood, as well as the ability to release CTCs controllably and alive. Clinical tests substantiate the accurate differentiation between liver cancer, cirrhosis, and healthy groups using this method. The remarkable diagnostic accuracy (94%), lossless release of CTCs, material reversibility, and cost-effectiveness ($6.68 per sample) make the HH-based hydrogel a potentially revolutionary technology for liver cancer diagnosis and single-cell analysis.

Intense Left-handed Circularly Polarized Luminescence in Chiral Nematic Hydroxypropyl Cellulose Composite Films.

Integrating optically active components into chiral photonic cellulose to fabricate circularly polarized luminescent materials has transformative potential in disease detection, asymmetric reactions, and anticounterfeiting techniques. However, the lack of cellulose-based left-handed circularly polarized light (L-CPL) emissions hampers the progress of these chiral functionalizations. Here, this work proposes an unprecedented strategy: incorporating a chiral nematic organization of hydroxypropyl cellulose with robust aggregation-induced emission luminogens to generate intense L-CPL emission. By utilizing N,N-dimethylformamide as a good solvent for fluorescent components and cellulose matrices, this work produces a right-handed chiral nematic structure film with a uniform appearance in reflective and fluorescent states. Remarkably, this system integrates a high asymmetric factor (0.51) and an impressive emission quantum yield (55.8%) into one fascinating composite. More meaningfully, this approach is versatile, allowing for the incorporation of luminogen derivatives emitting multicolored L-CPL. These chiral fluorescent films possess exceptional mechanical flexibility (toughness up to 0.9 MJ m-3) and structural stability even under harsh environmental exposures, making them promising for the fabrication of various products. Additionally, these films can be cast on the fabrics to reveal multilevel and durable anticounterfeiting capabilities or used as a chiral light source to induce enantioselective photopolymerization, thereby offering significant potential for diverse practical applications.

Order-order assembly transition-driven polyamines detection based on iron-sulfur complexes.

Innovative modes of response can greatly push forward chemical sensing processes and subsequently improve sensing performance. Classical chemical sensing modes seldom involve the transition of a delicate molecular assembly during the response. Here, we display a sensing mode for polyamine detection based on an order-order transition of iron-sulfur complexes upon their assembly. Strong validation proves that the unique order-order transition of the assemblies is the driving force of the response, in which the polyamine captures the metal ion of the iron-sulfur complex, leading it to decompose into a metal-polyamine product, accompanied by an order-order transition of the assemblies. This mechanism makes the detection process more intuitive and selective, and remarkably improves the detection efficiency, achieving excellent polyamines specificity, second-level response, convenient visual detection, and good recyclability of the sensing system. Furthermore, this paper also provides opportunities for the further application of the iron-sulfur platform in environment-related fields.

H2O2 and Phosphorylated Peptide Dual-Responsive Nanochannel Device.

Oxidation and protein phosphorylation are critical mechanisms involved in regulating various cellular activities. Increasing research has suggested that oxidative stress could affect the activities of specific kinases or phosphatases, leading to alterations in the phosphorylation status of certain proteins. Ultimately, these alterations can affect cellular signaling pathways and gene expression patterns. However, the relationship between oxidation and protein phosphorylation remains complex and not yet fully understood. Therefore, the development of effective sensors capable of detecting both oxidation and protein phosphorylation simultaneously presents an ongoing challenge. To address this need, we introduce a proof-of-concept nanochannel device that is dual-responsive to both H2O2 and phosphorylated peptide (PP). Specifically, we design a peptide GGGCEG(GPGGA)4CEGRRRR, which contains an H2O2-sensitive unit CEG, an elastic peptide fragment (GPGGA)4, and a phosphorylation site recognition fragment RRRR. When the peptides are immobilized on the inner walls of conical nanochannels in a polyethylene terephthalate membrane, this peptide-modified nanochannel device exhibits a sensitive response to both H2O2 and PPs. The peptide chains undergo a random coil-to-α-helix transition in response to H2O2, which leads to a close-to-open transition of the nanochannel, accompanied with a remarkable increase in the transmembrane ionic current. In contrast, binding of the peptides with PPs shields the positive charge of the RRRR fragments, causing a decrease of the transmembrane ionic current. These unique features enable the sensitive detection of reactive oxygen species released by 3T3-L1 cells stimulated by platelet-derived growth factor (PDGF) as well as PDGF-induced change in the PP level. Real-time kinase activity monitoring further confirms the device's potential utility for kinase inhibitor screening.

Nanofluidic Device for Detection of Lysine Methylpeptides and Sensing of Lysine Methylation.

Protein methylation is the smallest possible yet vitally important post-translational modification (PTM). This small and chemically inert addition in proteins makes the analysis of methylation more challenging, thus calling for an efficient tool for the sake of recognition and detection. Herein, we present a nanofluidic electric sensing device based on a functionalized nanochannel that was constructed by introducing monotriazole-containing p-sulfonatocalix[4]arene (TSC) into a single asymmetric polymeric nanochannel via click chemistry. The device can selectively detect lysine methylpeptides with subpicomole sensitivity, distinguish between different lysine methylation states, and monitor the lysine methylation process by methyltransferase at the peptide level in real time. The introduced TSC molecule, with its confined asymmetric configuration, presents the remarkable ability to selectively bind to lysine methylpeptides, which, coupled with the release of the complexed Cu ions, allows the device to transform the molecular-level recognition to the discernible change in ionic current of the nanofluidic electric device, thus enabling detection. This work could serve as a stepping stone to the development of a new methyltransferase assay and the chemical that specifically targets lysine methylation in PTM proteomics.

Halogen Bond-Driven Aggregation-Induced Emission Skeleton: N-(3-(Phenylamino)allylidene) Aniline Hydrochloride.

Aggregation-induced emission (AIE) is a unique photophysical process, and its emergence brings a revolutionary change in luminescence. However, AIE-based research has been limited to a few classical molecular skeletons, which is unfavorable for in-depth studies of the photophysical characteristics of AIE and the full exploitation of their potential values. There is an urgent need to develop new skeletons to rise to the challenges of an insufficient number of AIE core structures and difficult modification. Here, we report a novel dumbbell AIE skeleton, in which two phenyls are connected through (E)-3-iminoprop-1-en-1-amine. This skeleton shows extremely strong solid-state emission with an absolute quantum yield up to 69.5%, a large Stokes shift, and typical AIE characteristics, which well resolves the challenge of difficult modification and low luminous efficiency of the traditional AIE skeletons. One-step reaction, high yield, and diversified modification endow the skeleton with great scalability from simple to complicated, or from symmetrical to asymmetrical structures, which establishes the applicability of the skeleton in various scenarios. These molecules self-assemble into highly ordered layer-, rod-, petal-, hollow pipe-, or helix-like nanostructures, which contribute to strong AIE emission. Crystallographic data reveal the highly ordered layer structures of the aggregates with different substituents, and a novel halogen bond-driven self-assembly mechanism that restricts intramolecular motion is clearly discovered. Taking advantage of these merits, a full-band emission system from green to red is successfully established, which displays great potential in the construction of light-emitting films and advanced light-emitting diodes. The discovery of this AIE skeleton may motivate a huge potential application value in luminescent materials and lead to hitherto impossible technological innovations.

Visible and Reversible Restrict of Molecular Configuration by Copper Ion and Pyrophosphate.

Molecular configuration strongly impacts on its functions; however, due to complicated and diverse configuration as well as easy and rapid conversion among various configurations, research of molecular configuration is extremely difficult. If the free rotation of a molecule could be "slowed down" or even "frozen" by an external stimulus, such as ultralow temperature, then one configuration of the molecule could be captured and characterized relatively easily. Here, we show that the rotation of a hemicyanine-labeled 2-(2'-hydroxyphenyl)-4-methyloxazole (H-HPMO) molecule could be specifically and reversibly restricted by sequential additions of copper ion (Cu2+) and pyrophosphate (P2O74-), reflecting as remarkable fluorescence quenching and recovery, which could be directly observed by naked eyes. Binding affinity tests and cryogenic 1H NMR indicate that Cu2+ forms intensive coordinate bonds with phenolic hydroxyl, oxazole, and methoxyl groups of HPMO, which strongly restricts the free rotations of these groups and blocks charge transfer. This study provides a precise, rapid, visible, reversible, and low-cost method to monitor the molecular configuration, indicating the broad application prospects of near-infrared fluorescent sensors in configuration analysis, biosensing, and drug-substrate complexation.

A novel near-infrared turn-on fluorescent probe for the detection of Fe3+ and Al3+ and its applications in living cells imaging.

In this study, a new hemicyanidine-based colorimetric-fluorescent probe L has been synthesized and characterized by X-ray single crystal diffraction, NMR, HRMS and other technologies. The probe L serves as a "turn-on" probe for the detection of Fe3+ and Al3+ ions in DMF-HEPES system with a high sensitivity and an excellent selectivity. The probe L manifesting the color of the solution containing L turns red on the addition of Fe3+, and turns pink on the addition of Al3+. The fluorescence turn-on detection of Fe3+ and Al3+ ions is attributed to the photo-induced electron transfer (PET) process and the exertion of the chelation-enhanced fluorescence effect (CHEF) mechanism. The results of thin layer silica gel plate coloration experiments also present the same characteristics. Additionally, we further demonstrate that the probe L exhibit good cell permeability and could be employed to monitor Fe3+ and Al3+ ions in the living cells.

Fluorescent schiff base probes for sequential detection of Al3+ and F- and cell imaging applications.

Two novel Schiff-base fluorescent probers SQ and NQ based on 8-hydroxyquinoline moiety were designed and synthesized. The both probes were capable of binding with Al3+ by naked eye detection to produce a significant fluorescence enhancement response with a detection limit of 1.48 × 10-8 and 4.23 × 10-8 M, respectively. At the same time, the formed complexes SQ-Al3+ and NQ-Al3+ could sequentially detect F-, and the detection limits of F- were determined to be 1.64 × 10-7 and 3.58 × 10-8 M, respectively. The "off-on-off" fluorescence response process demonstrated that the binding were reversible. The probes were further successfully utilized to detect Al3+ and F- in vitro PC12 cells.

A dual fluorescence probe for Zn2+ and Al3+ through differentially response and bioimaging in living cells.

A novel Schiff base fluorescent probe 7-Hydroxy-8-(((2-(hydroxymethyl)quinolin-8-yl)imino)methyl)-coumarin (XL) consist of formylcoumarin and aminoquinoline moieties was synthesized for dual detection of Zn2+ and Al3+ ions. Probe XL exhibited high selective and sensitive response towards Zn2+ and Al3+ ions through different color changes and significant fluorescence turn-on response (270 fold higher for Zn2+ and 230 fold higher for Al3+) in MeOH-H2O (4/1, v/v) over other cations, with detection limits (LOD) as low as 3.75 × 10-8 and 1.14 × 10-8 M, respectively. Moreover, probe XL exhibited preferential selectivity for Al3+ through displacing Zn2+ from the XL-Zn2+ complex by ligand-to-ligand transfer process. The binding mechanism of intramolecular charge transfer (ICT) were proposed from fluorescence and UV-vis titrations, Job's plot, 1H NMR titration, HRMS and DFT calculations. The probe was proven to be suitable for actual samples detection of Zn2+ and Al3+ ions. The complex XL-Zn2+ and XL-Al3+ exhibited dramatic fluorescent "turn-off" properties for PPi and PPi/F- respectively through snatching metal ions and released free XL. Moreover, probe XL showed low biotoxicity and sequentially "off-on-off" fluorescent bio-imaging of Zn2+/Al3+ and PPi/F- in PC12 cells.

Coumarin-based colorimetric-fluorescent sensors for the sequential detection of Zn2+ ion and phosphate anions and applications in cell imaging.

Two novel coumarin based fluorescent sensors CHP and CHS have been synthesized for the sequential detection of Zn2+ ion and phosphate anion (PA) in DMF/HEPES buffer medium (1/5 v/v, 10 mM, pH = 7.4). On the addition of Zn2+ ion to the solution of CHP or CHS resulted in a pronounced fluorescence enhancement, accompanying noticeable color change (under UV or daylight), while there was hardly obvious change with other competing metal ions co-existing. The detection limits (DL) of CHP and CHS toward Zn2+ were separately determined as 1.03 × 10-7 (R2 = 0.9886) and 1.87 × 10-7 (R2 = 0.9902). The PET binding processes were affirmed by spectroscopic techniques, HRMS experiments and theoretical calculations. Subsequently, the CHP-Zn2+ or CHS-Zn2+ complexes showed high selectivity fluorescence quenching toward PA by snatching Zn2+ ion from its complex and the binding processes were reversible. DLs were calculated as 2.07 × 10-7 M (R2 = 0.9928) and 2.63 × 10-7 M (R2 = 0.9954), respectively. Furthermore, the cell imaging experiments demonstrated that the sensors were capable of detecting of Zn2+ and PA in vitro cells.

Indole-based colori/fluorimetric probe for selective detection of Cu2+ and application in living cell imaging.

A highly sensitive and selective indole-based probe IHT exhibited obvious color change from colorless to violet easily detected by naked eye as well as 'turn on' fluorescence response to Cu2+ ion at physiological pH condition. The detection limit was determined to be as low as 8.93 × 10-8 M, which was much lower than drinking water permission concentrations by the United States Environmental Protection Agency. The 1:2 binding mechanism was well confirmed by fluorescence titration, Job's plot, HRMS, IR analysis and DFT calculations. Furthermore, the probe IHT was successfully used for fluorescence imaging of Cu2+ ion in living cells.

A novel fluorescent-colorimetric probe for Al3+ and Zn2+ ion detection with different response and applications in F- detection and cell imaging.

A novel Schiff base fluorescence probe (HL) was synthesized by the condensation of salicylaldehyde and an 8-aminoquinoline derivative. This probe acts as a "turn-on" dual selectivity fluorescence probe for Zn2+ and Al3+ ions, providing different colors and detection limits (DL) of 11.5 and 23.5 nM, respectively. Moreover, when Zn2+ and Al3+ co-exist, HL exhibits a preference for Al3+ by displacing Zn2+ from the HL-Zn2+ complex, realizing a dual-channel signal output for Al3+. The HL-Al3+ system could further discern F- by a "turn-off" fluorescence response with a DL of 86.0 nM. Furthermore, the probe HL was capable of monitoring intracellular Al3+, Zn2+ and F- in living PC12 cells in vitro through fluorescence imaging, which proved its value in potential in vivo applications.

A novel colorimetric-fluorescent probe for Al3+ and the resultant complex for F- and its applications in cell imaging.

A novel quinoline-based Schiff-base probe QL had been synthesized, which could sequentially monitor Al3+ and F- in MeOH-H2O solution (v/v = 8/1, 0.01 M, HEPES buffer, pH = 7.3). The probe QL expressed a high selective and sensitive "OFF-ON-OFF" fluorescent response for Al3+ and F- (excitation at 460 nm and emission at 530 nm) accompanying visible color changed, which was ascribed to intramolecular charge transfer (ICT) process and chelation-enhanced fluorescence (CHEF) mechanism. The binding stoichiometry of QL with Al3+ was 2:1 counting on Job's plot and HRMS, while F- could pull Al3+ to depart from the complexation 2QL-Al3+ and released free QL. The limit of detections of probe QL for Al3+ and F- ions were calculated to be 0.10 µM and 0.50 µM. The 1H NMR experiments and density functional theory (DFT) calculations were carried out to further prove the binding mode between QL and Al3+. Furthermore, fluorescence imaging studies demonstrated that the probe QL was low cytotoxicity and could be applied to detect Al3+ and F- in living PC12cells.

A novel coumarin-based fluorescent sensor for Ca2+ and sequential detection of F- and its live cell imaging.

A novel fluorescent sensor CPM for relay detecting Ca2+ and F- based on coumarin has conveniently synthesized and characterized. The sensor CPM showed highly fluorescence enhancement to Ca2+ over other metal ions, and the CPM-Ca2+ complex could selectively recognize F- among other anions. The limits of detection for Ca2+ and F- were 5.81 × 10-7 M and 4.28 × 10-7 M in aqueous solution (DMF/HEPES buffer 1:1 v/v, 10 mM, pH = 7.2), respectively. Their sensing mode had been testified by Job's plots, UV-vis titration, 1H NMR titrations, ESI-mass, fluorescence and DFT calculations. The fluorescence imaging indicated that CPM was cell-permeable and could be used to effectively detect Ca2+ and F- within living cells.

Novel fluorescent probes for relay detection copper/citrate ion and application in cell imaging.

Two novel fluorescent probes, 2­(2'­hydroxyphenyl)­4­(2'­hydroxymethyl­8­quinolinamino)methyloxazole (L1), and 2­(2'­hydroxyphenyl)­4­(2'­methyl­8­quinolinamino)methyloxazole (L2), exhibited colorimetric and "turn off" fluorometric response to Cu2+ ion in DMSO/H2O solution (v/v = 1/1, 0.01 M, Tris-HCl buffer, pH 7.20) and the corresponding detection limit were found to be 2.14 × 10-8 and 2.70 × 10-8 M, which were much lower than drinking water permission concentrations by the United States Environmental Protection Agency (U.S. EPA) and World Health Organization (WHO). The L1-Cu2+ and L2-Cu2+ complexes ensemble detected citrate anions (CA) sequentially through fluorescence recovery response due to the extrusion of Cu2+ ion from the complexes. The binding processes were investigated by UV-vis, fluorescence, IR and DFT calculation. Furthermore, the vivo sensitivity experiments of Cu2+ ion and CA was demonstrated through fluorescence imaging in living cells.

A selective fluorescent probe for relay detection of Zn2+ and tartrate: Application to logic circuit and living cell imaging.

A novel fluorescent probe 2-(2'-hydroxyphenyl)-4-(phenylethylamino)methyloxazole (HPO) has been synthesized, which performed highly selective and sensitive detection of Zn2+ ion with a discriminating enhancement over the other metal ions. The binding constant was calculated as 3.07 × 103 M-1 with detection limit of 1.22 × 10-6 M in aqueous solution (CH3CN-Tris v/v, 1/1, Tris, 10 mM, pH = 7.4). Moreover, the HPO-Zn2+ complex could serve as an excellent tartrate anion (TA). The detection mode maybe due to TA detach Zn2+ ion from HPO-Zn2+ complex leading to resulting in the release of the free probe HPO. As a result, a logic circuit has also been constructed on the basis of Zn2+ and TA as chemical inputs. Furthermore, fluorescence imaging experiments showed that probe HPO could be used as an effective fluorescent probe for detecting Zn2+ and TA in living cells.

Colorimetric chiral fluorescent sensors for Eu3+ and sequential enantioselective sensing of malate anion.

Novel phenanthroline Schiff base fluorescent sensors L1, L2, and D1 were designed and synthesized. The sensing abilities of the compounds in the presence of metal cations (Li+ , Na+ , K+ , Ag+ , Mg2+ , Ba2+ , Ca2+ , Mn2+ , Pb2+ , Hg2+ , Ni2+ , Zn2+ , Cd2+ , Co2+ , Cu2+ , Cr3+ , Fe3+ , Fe2+ , Al3+ , and Eu3+ ) were studied by UV-vis and fluorescent spectroscopy. The compounds L1, L2, and D1 could act as Eu3+ ion turn-off fluorescent sensors based on ligand-to-metal binding mechanism in DMSO-H2 O solution (v/v = 1:1, 10 mM Tris, pH = 7.4). Additionally, the L1-Eu3+ and D1-Eu3+ complexes could be applied as turn-on enantioselective sensors sensing of malate anion isomers with color changes. Furthermore, biological experiments using living PC-12 cells demonstrated that L1 and D1 had excellent membrane permeability and could be used as effective fluorescent sensors for detecting Eu3+ and malate anion in living cells.