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Emerging liquid biopsy methods for investigating biomarkers in bodily fluids such as blood, saliva, or urine can be used to perform noninvasive cancer detection. However, the complexity and heterogeneity of exosomes require improved methods to achieve the desired sensitivity and accuracy. Herein, we report our study on developing a breast cancer liquid biopsy system, including a fluorescence sensor array and deep learning (DL) tool AggMapNet. In particular, we used a 12-unit sensor array composed of conjugated polyelectrolytes, fluorophore-labeled peptides, and monosaccharides or glycans to collect fluorescence signals from cells and exosomes. Linear discriminant analysis (LDA) processed the fluorescence spectral data of cells and cell-derived exosomes, demonstrating successful discrimination between normal and different cancerous cells and 100% accurate classification of different BC cells. For heterogeneous plasma-derived exosome analysis, CNN-based DL tool AggMapNet was applied to transform the unordered fluorescence spectra into feature maps (Fmaps), which gave a straightforward visual demonstration of the difference between healthy donors and BC patients with 100% prediction accuracy. Our work indicates that our fluorescent sensor array and DL model can be used as a promising noninvasive method for BC diagnosis.

Deferasirox, an FDA-approved iron chelator, has gained increasing attention for use in anticancer and antimicrobial applications. Recent efforts by our group led to the identification of this core as an easy-to-visualize aggregation-induced emission platform, or AIEgen, that provides a therapeutic effect equivalent to deferasirox (

Changes in adenosine triphosphate (ATP) and peroxynitrite (ONOO–) concentrations have been correlated in a number of diseases including ischemia-reperfusion injury and drug-induced liver injury. Herein, we report the development of a fluorescent probe ATP-LW, which enables the simultaneous detection of ONOO– and ATP. ONOO– selectively oxidizes the boronate pinacol ester of ATP-LW to afford the fluorescent 4-hydroxy-1,8-naphthalimide product NA-OH (λex = 450 nm, λem = 562 nm or λex = 488 nm, λem = 568 nm). In contrast, the binding of ATP to ATP-LW induces the spirolactam ring opening of rhodamine to afford a highly emissive product (λex = 520 nm, λem = 587 nm). Due to the differences in emission between the ONOO– and ATP products, ATP-LW allows ONOO– levels to be monitored in the green channel (λex = 488 nm, λem = 500–575 nm) and ATP concentrations in the red channel (λex = 514 nm, λem = 575–650 nm). The use of ATP-LW as a combined ONOO– and ATP probe was demonstrated using hepatocytes (HL-7702 cells) in cellular imaging experiments. Treatment of HL-7702 cells with oligomycin A (an inhibitor of ATP synthase) resulted in a reduction of signal intensity in the red channel and an increase in that of the green channel as expected for a reduction in ATP concentrations. Similar fluorescence changes were seen in the presence of SIN-1 (an exogenous ONOO– donor).

Here, we report a β-galactosidase (β-Gal)-responsive photochromic fluorescent probe, NpG, that was designed to prebind to human serum albumin (HSA) to form the probe/protein hybrid, NpG@HSA. The formation of NpG@HSA led to an increase in fluorescence emission (520 nm) corresponding to the binding of the fluorescent naphthalimide unit with HSA. In addition, this enabled visualization of the spiropyran fluorescence emission in aqueous media. Our probe/protein hybrid approach afforded a unique imaging platform with enhanced cell permeability and solubility that was capable of visualizing the cellular uptake of NpG@HSA before its activation by β-Gal. The β-Gal-mediated cleavage of the galactose unit within the NpG@HSA hybrid resulted in the formation of NpM@HSA and an increase in red fluorescence emission (620 nm). The resultant merocyanine unit was then able to undergo photoisomerization (merocyanine ↔ spiropyran) to facilitate STORM (i.e., stochastic optical reconstruction microscopy) imaging with minimal phototoxicity and excellent photostability/reversibility. Using STORM, NpG@HSA was able to determine the subcellular distribution of β-Gal activity between cell lines with nanoscale precision. We believe that this system represents a versatile imaging platform for the design of photochromic fluorescent probes suitable for illuminating the precise location of disease-specific biomarkers in various cellular processes.

As a result of their high specificity for their corresponding biological targets, peptides have shown significant potential in a range of diagnostic and therapeutic applications. However, their widespread use has been limited by their minimal cell permeability and stability in biological milieus. We describe here a hepta-dicyanomethylene-4H-pyran appended β-cyclodextrin (DCM(7)-β-CD) that acts as a delivery enhancing “host” for 1-bromonaphthalene-modified peptides, as demonstrated with peptide probes P1–P4. Interaction between the fluorescent peptides P1–P3 and DCM(7)-β-CD results in the hierarchical formation of unique supramolecular architectures, which we term supramolecular-peptide-dots (Spds). Each Spd (Spd-1, Spd-2, and Spd-3) was found to facilitate the intracellular delivery of the constituent fluorescent probes (P1–P3), thus allowing spatiotemporal imaging of an apoptosis biomarker (caspase-3) and mitosis. Spd-4, incorporating the antimicrobial peptide P4, was found to provide an enhanced therapeutic benefit against both Gram-positive and Gram-negative bacteria relative to P4 alone. In addition, a fluorescent Spd-4 was prepared, which revealed greater bacterial cellular uptake compared to the peptide alone (P4-FITC) in E. coli. (ATCC 25922) and S. aureus (ATCC 25923). This latter observation supports the suggestion that the Spd platform reported here has the ability to facilitate the delivery of a therapeutic peptide and provides an easy-to-implement strategy for enhancing the antimicrobial efficacy of known therapeutic peptides. The present findings thus serve to highlight a new and effective supramolecular delivery approach that is potentially generalizable to overcome limitations associated with functional peptides.

Currently, chemotherapy is a widely used and important treatment for cancer. However, almost all of the treatments have shortcomings associated with poor specificity and high toxicity, which results in severe side effects to normal cells and tissue. This is a very important problem, and yet, it currently remains unanswered. Therefore, the development of the method for the more effective delivery of anticancer drugs to their targets and real-time monitoring of the localization of the drugs are very important. Herein, we designed a theranostic prodrug: CPT-p-Leu, which was constructed using fluorescent camptothecin (CPT), a self-immolative linker and leucine (Leu) residue. Upon exposure to LAP (leucine aminopeptidase: LAP), the amide bond in CPT-p-Leu will be cleaved, followed by an intramolecular 1,6-elimination, which triggers the active anticancer drug (CPT) release and recovers the fluorescence of CPT. With our design, the anticancer drug, CPT, can be used as both a drug and a fluorescence reporter, making our system suitable to accurately and effectively track the released CPT distribution. Based on this strategy, CPT-p-Leu could achieve the chemoselective detection of LAP and monitoring of the anticancer drug release. Furthermore, it also provides a very convenient way to accurately determine the location of the released drug in living samples. In addition, CPT-p-Leu shows a good cell membrane permeability and enhanced cytotoxicity toward LAP overexpressing cancer cells. We anticipate that our research will facilitate the development of improved theranostic systems for cancer therapy.

Deferasirox, ExJade, an FDA-approved treatment for iron overload disorders has been shown to inhibit the growth of both gram-positive and -negative bacteria through iron (Fe(III)) chelation. Modification of the ExJade framework led to the identification of a new fluorescent platform ExPh and ExBT. Functionalization of the phenol moieties on ExBT with phosphate units afforded a ratiometric fluorescent pro-chelator (ExPhos), which was effective in the inhibition of two clinically relevant antibiotic-resistant bacteria, (MRSA (ATCC 43300) and VRE (ATCC 51299)), and allowed the fluorescent imaging of MRSA. Remarkably, this pro-chelation strategy proved selective towards bacteria with no cytotoxicity observed for ExPhos treated A549 cells (72 h incubation). This work represents a new pro-chelator antibiotic strategy that can be modified with a chosen reactive chemical trigger to provide a diagnostic signal in conjunction with a therapeutic response with a potential of minimal off-target toxicities.

The seasonal outbreak of influenza causes significant morbidity and mortality worldwide because a number of influenza virus (IV) strains have been shown to infect and circulate in humans. Development of effective means to timely monitor as well as block IVs is still a challenging task. Whereas conventional fluorescence probes rely on a fluorimetric change upon recognizing IVs, here we developed simple "Supra-dots" that are formed through the aqueous supramolecular assembly between a blue-emitting polymer dot and red-emitting sialylglycan probes for the ratiometric detection of IVs. Tuning the Förster resonance energy transfer from polymer dots to glycan probes by selective sialylglycan-virus recognition enables the fluorescence ratiometric determination of IVs, whereas the presence of unselective, control viruses quenched the fluorescence of the Supra-dots. Meanwhile, we show that the Supra-dots can effectively inhibit the invasion of a human-infecting IV toward a human cell line, thereby making possible a unique bifunctional, supramolecular probe for influenza theranostics.

Photoresponsive smart surfaces are promising candidates for a variety of applications in optoelectronics and sensing devices. The use of light as an order signal provides advantages of remote and noninvasive control with high temporal and spatial resolutions. Modification of the photoswitches with target biomacromolecules, such as peptides, DNA, and small molecules including folic acid derivatives and sugars, has recently become a popular strategy to empower the smart surfaces with an improved detection efficiency and specificity. Herein, we report the construction of photoswitchable self-assembled monolayers (SAMs) based on sugar (galactose/mannose)-decorated azobenzene derivatives and determine their photoswitchable, selective protein/cell adhesion performances via electrochemistry. Under alternate UV/vis irradiation, interconvertible high/low recognition and binding affinity toward selective lectins (proteins that recognize sugars) and cells that highly express sugar receptors are achieved. Furthermore, the cis-SAMs with a low binding affinity toward selective proteins and cells also exhibit minimal response toward unselective protein and cell samples, which offers the possibility in avoiding unwanted contamination and consumption of probes prior to functioning for practical applications. Besides, the electrochemical technique used facilitates the development of portable devices based on the smart surfaces for on-demand disease diagnosis.

A novel dual-function fluorescent probe (ATP-LW) was developed for the detection of ONOO- and ATP.

A simple ESIPT-based fluorescence probe (HMBT-LW) was developed for the detection of superoxide (O2⸱-). HMBT-LW was synthesised over two steps and was shown to rapidly detect low concentrations of O2⸱- (limit of detection = 7.4 μM), fully reacting within two minutes. Furthermore, HMBT-LW demonstrated excellent selectivity and sensitivity towards O2⸱-.

We show here that a series of triazolyl glycolipid derivatives modularly synthesized by a "click" reaction have the ability to increase the susceptibility of a drug-resistant bacterium to β-lactam antibiotics. We determine that the glycolipids can suppress the minimal inhibitory concentration of a number of ineffective β-lactams, upward of 256-fold, for methicillin-resistant Staphylococuss aureus (MRSA). The mechanism of action has been preliminarily probed and discussed.

This study describes the exploitation of click chemistry in the one-step molecular engineering of an unqualified rhodamine probe, leading to its considerable functional enhancement in terms of water solubility, ion selectivity, and usefulness in detecting biological and environmental samples. A dipropargyl rhodamine dye previously identified as an unselective and poorly water-soluble mercury(II) probe was used to couple with an azido polyethylene glycol (PEG) by the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition click reaction in almost quantitative yield. The simple click-engineered rhodamine probe shows, remarkably, better water solubility and mercury(II) selectivity comparing to the raw counterpart, and can be used to sensitively image mercury ions internalized by live cells and to accurately quantify the ion spiked in river water specimens. This study provides insights into the simple functional improvement of unqualified molecular dye probes via the efficient "click engineering".

Here, we describe a novel "switch-on" biosensor based on quinonyl glycosides functionalized quantum dots (QDs) for the specific targeting and imaging of transmembrane glycoprotein receptors on the surface of cancer cells. The design of the quinonyl glycosides lies in that the quinone moiety serves as a quencher of QDs and the glycoside moiety as a biospecific ligand for targeting a receptor. We observed that the quenched photoluminescence of the quinone glycosides functionalized QDs could be significantly recovered by a specific lectin that selectively binds to the glycosides clustering the QDs but was not affected by a panel of nonspecific lectins. Moreover, we determined that quinonyl galactoside functionalized QDs could optically image the asialoglycoprotein receptors of a hepatoma cell line in a target-specific manner. This system might provide new insights into the fabrication of photoluminogenic biosensors for the analysis of the universal ligand-receptor recognitions in nature.

Developing an effective means for the real-time probing of amyloid β (Aβ) that is closely implicated in Alzheimer’s disease (AD) could help better understand and monitor the disease. Here we describe an economic approach based on the simple composition of a natural product, resveratrol (Res), with graphene oxide (GO) for the rapid, fluorogenic recognition of Aβ. The Res@GO composite has proved specific for Aβ over a range of proteins and ions, and could sensitively capture both Aβ monomers and fibers in a physiological buffer solution within only 3 min. The composite can also fluorescently image amyloid deposits in a mouse brain section within 30 min. This new protocol is much cheaper and more timesaving than the conventional immunofluorescence staining technique employed clinically, providing an economic tool for the concise detection of AD.

Extensive efforts have been devoted to the qualification of plant extracts as green corrosion inhibitors for industrial metals, but studies that demonstrate the active component(s) of these extracts remain scarce. We report here that piperine, the major pungent component of peppers, has the best corrosion inhibitive efficiency for copper in HCl among four analogous amide alkaloids isolated from a traditional Chinese medicine. This compound inhibited HCl corrosion more efficiently than cysteine, and did not exhibit markedly decreased efficiency under several harsh experimental conditions. Electrochemical and microscopic analyses suggested that piperine could form a protective layer on the metal surface via both physisorption and chemisorption, reducing the corrosion rate. The adsorption energies of all the test compounds were calculated using a hybrid density functional theory.

Despite natural amino acids having been proposed as the green surrogate of currently used corrosion inhibitors that are generally toxic to both nature and human body during the everyday industrial processing of metallic equipments, their structural simplicity yet lowers the inhibitive potency, thereby hampering their further industrialization. We disclose here that a concise chemical ligation (CuI-catalyzed azide–alkyne 1,3-dipolar cycloaddition reaction [Cue-AAC]) between two l-amino acids that are weak or noncorrosion inhibitors may result in their largely improved protective effect for mild steel in HCl. A series of 1,4-disubstituted 1,2,3-triazolyl bis-amino acid derivatives constituted by l-serine, l-threonine, l-phenylalanine, and l-tyrosine were efficiently synthesized via Cue-AAC and deprotection reactions in high yields. Subsequently performed electrochemical impedance spectroscopy (EIS) evidenced that the inhibitive effect of these compounds for mild steel in 1 M HCl is markedly better than that...