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This tutorial review provides a general overview for the design of prodrugs and activatable phototherapeutics which enables the development of improved therapies.

A supramolecular glycomaterial has been developed using the self-assembly of pyrenyl glycosides and graphene nanoribbon-based nanowires for the targeted, photothermally-controlled release of antibiotics to bacteria.

Chemical warfare agents (CWAs) are toxic chemicals that have been intentionally developed for targeted and deadly use on humans. Although intended for military targets, the use of CWAs more often than not results in mass civilian casualties. To prevent further atrocities from occurring during conflicts, a global ban was implemented through the chemical weapons convention, with the aim of eliminating the development, stockpiling, and use of CWAs. Unfortunately, because of their relatively low cost, ease of manufacture and effectiveness on mass populations, CWAs still exist in today's world. CWAs have been used in several recent terrorist-related incidents and conflicts (

A turn-on isatin receptor based naphthalimide fluorescent probe encapsulated in PEG was used to rapidly detect peroxynitrite in cells.

Luminogens characteristic of aggregation-induced emission (AIEgens) have been extensively exploited for the development of imaging-guided photodynamic therapeutic (PDT) agents. However, intramolecular rotation of donor-acceptor (D-A) type AIEgens favors non-radiative decay of photonic energy which results in unsatisfactory fluorescence quantum and singlet oxygen yields. To address this issue, we developed several molecularly engineered AIEgens with partially "locked" molecular structures enhancing both fluorescence emission and the production of triplet excitons. A triphenylphosphine group was introduced to form a D-A conjugate, improving water solubility and the capacity for mitochondrial localization of the resulting probes. Experimental and theoretical analyses suggest that the much higher quantum and singlet oxygen yield of a structurally "significantly-locked" probe (LOCK-2) than its "partially locked" (LOCK-1) and "unlocked" equivalent (LOCK-0) is a result of suppressed AIE and twisted intramolecular charge transfer. LOCK-2 was also used for the mitochondrial-targeting, fluorescence image-guided PDT of liver cancer cells.

A two-dimensional (2D) glycomaterial for targeted delivery of maytansine to liver cancer cells was developed.

Host–guest inclusion of a small-molecule fluorescent probe into human serum albumin enhances its sensitivity for ONOO− in aqueous solution and in cells.

An ESIPT-based ratiometric probe with solid-state luminescence enhancement is developed for the sensitive detection of glycosidase activity.

We report here strategic functionalization of the FDA approved chelator deferasirox (1) in an effort to produce organelle-targeting iron chelators with enhanced activity against A549 lung cancer cells. Derivative 8 was found to have improved antiproliferative activity relative to 1. Fluorescent cell imaging revealed that compound 8 preferentially localises within the lysosome.

Alkaline phosphatase (ALP) is an important enzyme-based biomarker present in several bacterial species; however, it is currently undervalued as a strategy to detect pathogenic bacteria. Here, we explore our ALP-responsive colorimetric and fluorescent probe (TCF-ALP) for such applications. TCF-ALP displayed a colorimetric and fluorescence response towards Staphylococcus aureus (S. aureus), with a limit of detection of 3.7 × 106 CFU mL−1 after 24 h incubation. To our surprise, TCF-ALP proved selective towards Staphylococcus bacteria when compared with Enterococcus faecalis (E. faecalis), and Gram-negative P. aeruginosa and E. coli. Selectivity was also seen in clinically relevant S. aureus biofilms. Owing to the high prevalence and surface location of S. aureus in chronic wounds, TCF-ALP was subsequently encapsulated in polyvinyl alcohol (PVA)-based hydrogels as a proof-of-concept “smart” wound dressing. TCF-ALP hydrogels were capable of detecting S. aureus in planktonic and biofilm assays, and displayed a clear colour change from yellow to purple after 24 h incubation using ex vivo porcine skin models. Overall, TCF-ALP is a simple tool that requires no prior knowledge, training, or specialist equipment, and has the potential to overcome issues related to invasive swabbing and tissue biopsy methods. Thus, TCF-ALP could be used as a tool to monitor the early development of infection in a wound and allow for the rapid provision of appropriate treatment for Staphylococcal bacterial infections.

We report on a supramolecular sensor array using fluorogenic peptide probes and graphene oxide that can target glycoproteins on a viral caspid, facilitating the differentiation of ebola virus from marburg virus and receptor-extensive vesicular stomatitis virus using principal component analysis.

In this study, "core-shell" gold nanoparticles (AuNPs) have been functionalised using a simple one-pot approach to form fucose-based glycoconjugate AuNPs (Fuc-AuNPs) and galactose-based glycoconjugate AuNPs (Gal-AuNPs), respectively. Owing to the selective carbohydrate-based recognition of the key virulence factors of P. aeruginosa, LecB (fucose-specific lectin)/LecA (galactose-specific lectin), Fuc-AuNPs and Gal-AuNPs-based imaging and therapeutic strategies were evaluated towards P. aeruginosa. Both Fuc-AuNPs and Gal-AuNPs were non-covalently loaded with the fluorophore dicyanomethylene 4H-pyran (DCM) to afford two highly selective fluorescence imaging agents for the visualisation of P. aeruginosa. The loading of Fuc-AuNPs and Gal-AuNPs with the known antibiotic Ceftazidime (CAZ) exhibited an enhanced therapeutic effect, illustrating the significance of this targeted drug delivery strategy. Exploiting the phototherapeutic properties of AuNPs, photoirradiation (600 nm) of Fuc-AuNP@CAZ/Gal-AuNP@CAZ provided both photothermal and photodynamic therapeutic (PTT/PDT) effects, which facilitated the release of CAZ. Fuc-AuNP@CAZ and Gal-AuNP@CAZ were shown to be effective photo/chemotherapeutics resulting in almost complete eradication of P. aeruginosa biofilms formed on clinically relevant surfaces (glass slides and steel surface).

Central nervous system (CNS) neurodegeneration is defined by a complex series of pathological processes that ultimately lead to death. The precise etiology of these disorders remains unknown. Recent efforts show that a mechanistic understanding of the malfunctions underpinning disease progression will prove requisite in developing new treatments and cures. Transition metals and lanthanide ions display unique characteristics (i.e., magnetism, radioactivity, and luminescence), often with biological relevance, allowing for direct application in CNS focused imaging modalities. These techniques include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and luminescent-based imaging (LumI). In this Tutorial Review, we have aimed to highlight the various metal-based imaging techniques developed in the effort to understand the pathophysiological processes associated with neurodegeneration. Each section has been divided so as to include an introduction to the particular imaging technique in question. This is then followed by a summary of key demonstrations that have enabled visualization of a specific neuropathological biomarker. These strategies have either exploited the high binding affinity of a receptor for its corresponding biomarker or a specific molecular transformation caused by a target species, all of which produce a concomitant change in diagnostic signal. Advantages and disadvantages of each method with perspectives on the utility of molecular imaging agents for understanding the complexities of neurodegenerative disease are discussed.

Cancer is among the leading causes of death worldwide. Although a number of new treatment options have been developed in recent years, there remains a need for improved chemotherapies. The primary challenges facing new cancer drugs include: (1) improving patient quality of life, (2) overcoming drug resistance and (3) lowering reoccurrence rates. Major drawbacks of current chemotherapeutics arise from poor selectivity towards cancer cells, dose limiting toxicities, compliance-reducing side effects, and an inability to address resistance mechanisms. Chemotherapeutics that fail to achieve complete eradication of the disease can also lead to relapse and promote treatment resistance. New strategies to overcome these drawbacks include the use of transition metal chelators and ionophores to alter selectively the concentrations of iron, copper, and zinc in cancer cells. A number of metal chelators have successfully demonstrated cytotoxicity and targeted activity against drug-resistant cancer cells; several have proved effective against cancer stem cells, a significant cause of tumour reoccurrence. However, problems with formulation and targeting have been noted. Recent efforts have thus focused on the design of pro-chelators, inactive versions of chelators that are designed to be activated in the tumour. This is an appealing strategy that may potentially increase efficacy towards cancer-resistant malignant cells. This Tutorial Review summarizes recent progress involving transition metal chelators, pro-chelators, and ionophores as potential cancer chemotherapeutics. We will focus on the reported agents that are able to coordinate iron, copper, and zinc.

Correction for ‘Fluorescent glycoconjugates and their applications’ by Baptiste Thomas et al., Chem. Soc. Rev., 2020, 49, 593–641, DOI: 10.1039/C8CS00118A.

With this research we set out to develop a number of coumarin-based ‘AND’ logic fluorescence probes that were capable of detecting a chosen analyte in the presence of HCys. Probe JEG-CAB was constructed by attaching the ONOO� reactive unit, benzyl boronate ester, to a HCys/Cys reactive fluorescent probe, CAH. Similarly, the core unit CAH was functionalised with the nitroreductase (NTR) reactive p-nitrobenzyl unit to produce probe JEG-CAN. Both, JEG-CAB and JEG-CAN exhibited a significant fluorescence increase when exposed to either HCys and ONOO� (JEG-CAB) or HCys and NTR (JEG-CAN) thus demonstrating their effectiveness to function as AND logic gates for HCys and a chosen analyte.

Traditional biochemical methods for enzyme detection are mainly based on antibody-based immunoassays, which lack the ability to monitor the spatiotemporal distribution and, in particular, the in situ activity of enzymes in live cells and in vivo. In this review, we comprehensively summarize recent progress that has been made in the development of small-molecule as well as material-based fluorogenic probes for sensitive detection of the activities of enzymes that are related to a number of human diseases. The principles utilized to design these probes as well as their applications are reviewed. Specific attention is given to fluorogenic probes that have been developed for analysis of the activities of enzymes including oxidases and reductases, those that act on biomacromolecules including DNAs, proteins/peptides/amino acids, carbohydrates and lipids, and those that are responsible for translational modifications. We envision that this review will serve as an ideal reference for practitioners as well as beginners in relevant research fields.

We have developed a novel AND logic based fluorescence probe for the simultaneous detection of ONOO− and GSH (GSH-PF3). The GSH-PF3 probe was synthesised over three steps starting from commercially available fluorescein. The probe was constructed by attaching the GSH reactive motif, 2,4-dinitrobenzenesulfonyl, to the previously reported boronate fluorescence based probe, PF3. GSH-PF3 produced only a small fluorescence response towards the addition of GSH or ONOO− separately. However, when the probe was exposed to both analytes, there was a significant (40-fold) fluorescence enhancement. GSH-PF3 demonstrated an excellent selectivity towards both GSH and ONOO−. In cellular imaging experiments the probe was shown to be cell permeable with no ‘turn-on’ response observed for the addition of either GSH or ONOO− separately. However, in the presence of both analytes, a clear fluorescence response was observed in live cells. GSH-PF3 was further able to monitor the co-existence of metabolically produced ONOO− and GSH by exogenous stimulation.

Bone grafting remains the method of choice for the majority of surgeons in the treatment of large bone defects, since it fills spaces and provides support to enhance biological bone repair. Recently, we have reported our research on a bioactive multiphase macroporous scaffold with interconnected porous structures and nano-crystal surface microstructures that can release bioactive ions. Moreover, we demonstrated the excellent in vitro biological activity of the scaffold. In this study, we set out to evaluate the in vivo osteogenesis and vascularization of the scaffold in the treatment of large bone defects (10 mm radial bone defect in rabbits). In comparison with the control group, X-ray and micro-CT results at the 4th and 8th week post-surgery reveal that the bioactive scaffold displayed an enhanced level of new bone and vessel formation. Histological results at the same weeks indicated improved bone formation, osseointegration and new vessel ingrowth inside the bioactive scaffold. These findings establish a good foundation for the potential clinical validation of the bioactive macroporous biomaterial scaffold for use as a bone substitute or in tissue engineering.

Traditionally, fluorescence probes have focused on the detection of a single biomarker for a specific process. In this work, we set out to develop a number of fluorescence probes that enable the detection of a chosen analyte in the presence of reactive oxygen/nitrogen species (ROS/RNS). These fluorescence probes when activated result in the formation of the highly fluorescent pink dye, resorufin. Therefore, we have labelled these fluorescent probes as ‘Pinkments’. Our first ‘Pinkment’ was shown to detect biologically relevant concentrations of ONOO− and have an excellent selectivity against other ROS/RNS. Pinkment-OH was developed to provide a core unit which could be easily functionalised to produce a range of ‘AND’ based fluorescence probes for the detection of ROS/RNS and a second analyte. For proof of concept, we synthesised Pinkment-OTBS and Pinkment-OAc. These ‘AND’-based probes were successfully shown to detect ROS/RNS and F− or esterase, respectively.

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˙−.

Three cationic conjugated polyelectrolytes (CPEs) with a common poly(p-phenylene ethynylene) backbone and different galactose-containing side chains were designed and synthesized. These CPEs were characterized and their application in targeted hepatoma cell imaging was demonstrated.

The development of small-molecule fluorescent probes for the detection of ions and biomacromolecules and for cellular and in vivo imaging has been a very active research area. Nevertheless, many problems exist for traditional probes including their poor water solubility, toxicity and the inability to target specific tissues. Because of the enhanced water solubility, biocompatibility and targeting ability for specific cells, there has been an emerging movement to use carbohydrates as either the backbone or as a warhead to decorate conventional fluorescent probes, producing "glycoprobes" with enhanced properties. This feature article provides an overview of recently developed glycoprobes for ion and protein detection as well as targeted (receptor targeting) cellular imaging and theranostics. Here, we summarise the tactics for preparing small molecular glycoprobes and their supramolecular 2D material composites.

The switch in glycan-receptor specificity of influenza viruses may cause their interspecies transmission. However, tools that can simultaneous unveil the different receptor specificities of a single virus strain, in a homogeneous solution, have been elusive. Here we show a simple yet effective “2D glycosheet” that is capable of simultaneously identifying the human- and avian-glycan-receptor specificity of influenza viruses. Two fluorophores with different emission colors are coupled with avian- or human-glycan receptors. Then, the glycan–fluorophore conjugates with different receptors and emission colors are co-assembled on a 2D molybdenum disulfide platform, producing a duplexed, fluorogenic 2D glycosheet. While the system shows a single emission color with viruses containing a single receptor specificity, in the presence of a virus (H7N9) containing dual (human- and avian-) receptor specificity the system produces both emission colors. Interestingly, the use of graphene oxide and carbon nanotubes as the material substrate also produces dual emission with H7N9, thus enabling a new generation of low-dimensional glycomaterials for effectively probing the switch in receptor-specificity of influenza viruses.

Here we demonstrate that low-dimensional materials (LDMs) enhance the conjugation between fluorogenic boronic acids (BAs) and saccharides. Among the LDMs investigated, 1D carbon nanotubes significantly lower the limit of detection and enhance the binding of the BA with D-fructose.

We have developed a theranostic nanocomposite of metallic nanoparticles that uses two distinct fluorescence mechanisms: Forster Resonance Energy Transfer (FRET) and Metal-Enhanced Fluorescence (MEF) controlled by ligand-receptor interaction. Supramolecular assembly of the fluorophore-labeled glycoligands to cyclodextrin-capped gold nanoparticles produces a nanocomposite with a quenched fluorescence due to FRET from the fluorophore to the proximal particle. Subsequently, interaction with a selective protein receptor leads to an aggregation of the composite, reactivating the fluorescence by MEF from the distal metallic particles to fluorophores encapsulated in the aggregates. The aggregation also causes a red-shift in absorbance of the composite, thereby enhancing the production of reactive oxygen species (ROS) on red-light irradiation. Our nanocomposite has proven suitable for targeted cancer cell imaging as well as multimode therapy using both the photodynamic and drug delivery properties of the composite.

Small-molecular probes capable of monitoring and interfering with the activity of biomacromolecules – such as polysaccharides, nucleotides and proteins – are of paramount importance to the advancement of life science. However, such probes that can detect and simultaneously modulate the construction of biomacromolecules are elusive. Here we report a fluorogenic, foldable glycoprobe that can recognize and assemble a protein receptor in a synchronous fashion. The glycoprobe synthesized by introducing a glycoligand (for protein recognition) to a bola-type bis-fluorophore conjugate shows a “self-shielded” fluorescence in the folded state. Association with a receptor protein rapidly unfolds the probe, releasing a fluorophore capable of crosslinking the proteins – as determined using small-angle X-ray scattering – thereby producing a unique fluorescent supramolecular construct. We have demonstrated the use of the foldable glycoprobe in order to track the endocytic cycle of a transmembrane receptor.

Industrial treatment (such as washing and rescaling) of copper-based equipment with acids requires the use of corrosion inhibitors to mitigate environmental pollution. However, the currently used organic inhibitors for copper, such as benzotriazole (BTA), are protonated in acidic solutions, thereby weakening the adsorption to a positively charged copper surface. Here we show that the use of an effective copper-ion chelator can overcome the repulsion between protonated inhibitors and a cationic copper surface in acidic solutions. With a variety of surface techniques including time of flight secondary ion mass spectrometry, X-ray photoelectron spectroscopy and X-ray diffraction, we determine that bis-triazolyl indoleamines (BTIs) can strongly coat onto a cationic copper surface in acidic solutions through chelation with Cu(I) species. The electrochemical techniques used suggest that the BTIs are much better corrosion inhibitors than BTA, showing consistently an outstanding inhibitive efficiency in spite of the reduction of the inhibitor concentration by 100-fold and the increase of solution temperature and acidic strength. A preliminary cell viability assay suggests that our BTI is much less toxic than BTA towards two healthy cell lines.

The synthesis of a series of new N-oxyamide-linked glycoglycerolipids and their assembly with gold nanoparticles for receptor-targeting imaging and drug delivery are reported.

We report an interlocked supramolecular ensemble formed between a conjugated polymer (CP) and a fluorescent glycoprobe for receptor-targeting cancer cell theranostics.

We demonstrate the use of an effective Diels–Alder reaction to produce a library of heterocyclic, polyaromatic benzo[c]carbazole derivatives with good corrosion inhibitive potency for copper against HCl.

Here we demonstrate the simple construction and characterization of a pyrenyl glycoside-coated 2D MoS2 material composite capable of selectively capturing proteins and live cells on an electrode, as determined by differential pulse voltammetry.

Here we demonstrate that 2D MoS2 can enhance the receptor-targeting and imaging ability of a fluorophore-labelled ligand. The 2D MoS2 has an enhanced working concentration range when compared with graphene oxide, resulting in the improved imaging of both cell and tissue samples.

This review summarizes the recent progress in quantum dot (QD) based sensors used for the photoluminescent detection of a variety of species in vitro and in vivo. New trends in using these nanomaterials for sensing applications are highlighted.

With this research we demonstrate that glycosylation of a naphthalimide zinc ion probe, using click chemistry, leads to an improvement of the aqueous sensitivity, working pH range and targeting ability for specific cells, together with significantly reduced cytotoxicity.

Construction of composite materials based on the self-assembly of fluorescently labeled biomolecules with a variety of micro- or nano-quenching materials (by the Förster Resonance Energy Transfer mechanism) for the fluorogenic recognition of disease-related proteins has become a dynamic research topic in the field of fluorescence recognition. Here we summarize the recent progress on the composition of fluorescence dye-labeled biomolecules including sugars, peptides and nucleotides with organic (graphene and carbon nanotubes) and inorganic (gold nanoparticles) materials. Their application in the fluorescence detection of proteins and enzymes on both the molecular and cellular levels is discussed. Perspectives are proposed with respect to the future directions of employing these composite materials in the recognition of pathological proteins.

Recently, there has been increasing interest in the construction of graphene oxide (GO) based fluorogenic composite materials (FCMs) for the detection of ligand-protein recognitions, which modulate numerous physiological and pathological processes in nature. In the sensing systems developed, GO has been used as a platform to assemble, and thus quench the fluorescence of dye-labelled ligands for the fluorogenic (fluorescence off-on) detection of proteins through the competitive formation of ligand-protein complexes, disassembling the GO composite. Here we show that the size, structure and loading concentration of GO may largely impact the sensing performance of GO-based FCMs. We synthesized four glycodyes that incorporate diverse natural glycoligands (as recognition groups) coupled with fluorescent dyes (as both the graphene binding and signal reporting group) with different emission wavelengths for comparison with GOs with different sizes. We determined that with the increase of size, the quenching ability of GO for the glycodyes increased, whereas the GO with a moderate size showed the best sensing performance for lectins (proteins that recognize glycoligands). The plausible mechanism of action was proposed. This research suggests that judicious quality control of GO is crucial for the construction of GO-based FCMs as biosensors.

We have developed a galactosyl azidonaphthalimide probe for the selective fluorogenic imaging of hepatocellular H2S, an important gaseous transmitter produced in the liver.

Correction for ‘Glycosylation enhances the aqueous sensitivity and lowers the cytotoxicity of a naphthalimide zinc ion fluorescence probe’ by Lei Dong et al., Chem. Commun., 2015, DOI: 10.1039/c5cc04357c.

Bis-triazolyl indoleamine-based chemosensors that respond to copper, and then fluorine as presumably facilitated by the high-affinity interaction between F(-) and the NH-proton of indole, are reported. Remarkable fluorimetric as well as colorimetric alternations upon the specific ligand-ion recognitions were observed.

There has been increasing interest in the development of protein tyrosine phosphatase 1B (PTP1B) inhibitors for the treatment of type 2 diabetes, obesity and breast cancer. We report here the identification of a series of mono- and bis-phenylalaninyl and tyrosinyl glucoside derivatives as novel PTP1B inhibitors. The designed compounds bearing one or two phenylalanine or tyrosine derivatives on the 6-, 2,3-, 2,6-, 3,4- and 4,6-positions of the glucosyl scaffolds were efficiently constructed via the microwave-assisted Cu(I)-catalyzed azide–alkyne cycloaddition in moderate-to-excellent yields. Successive biological assays identified these compounds as novel PTP1B inhibitors, with the 4,6-disubstituted tyrosinyl glucoside being the most potent. A kinetic study established that both mono- and bis-triazole-linked glycosyl acids act as typical competitive inhibitors whereas the bis-triazolyl ester that also exhibited inhibitory activity on PTP1B displayed a mixed-type inhibition pattern. Furthermore, docking simulation plausibly proposed the diverse binding modes of these compounds with the enzymatic target.