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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.

We would like to welcome you to the wonderful world of fluorescent chemosensors. This book consists of 16 chapters that take you on a journey from receptor-based to reaction-based sensing systems. The quest includes both molecular-based and nanoparticle-based systems that can be used for medical diagnostics, theranostics and environmental sensing applications. The techniques included embrace two-photon fluorescence, ratiometric and aggregation-induced emission.

Due to their simplicity in preparation, sensitivity and selectivity, fluorescent probes have become the analytical tool of choice in a wide range of research and industrial fields, facilitating the rapid detection of chemical substances of interest as well as the study of important physiological and pathological processes at the cellular level. In addition, many long-wavelength fluorescent probes developed have also proven applicable for in vivo biomedical applications including fluorescence-guided disease diagnosis and theranostics (e.g., fluorogenic prodrugs). Impressive progresses have been made in the development of sensing agents and materials for the detection of ions, organic small molecules, and biomacromolecules including enzymes, DNAs/RNAs, lipids, and carbohydrates that play crucial roles in biological and disease-relevant events. Here, we highlight examples of fluorescent probes and functional materials for biological applications selected from the special issues “Fluorescent Probes” and “Molecular Sensors and Logic Gates” recently published in this journal, offering insights into the future development of powerful fluorescence-based chemical tools for basic biological studies and clinical translation.

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 (

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.

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.

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).

We report on a superoxide anion (O2˙−) responsive fluorescent probe called TCF-OTf.

Background Chylothorax is a rare but serious complication of esophagectomy that can be life threatening if not addressed in a timely fashion. Chylous leakage generally occurs in response to thoracic duct injury, and anatomical variations in thoracic duct structure can add to the risk of injury during esophageal surgery. Here, we report a rare occurrence of refractory chylothorax after esophagectomy and discuss the diagnostic strategy and aggressive surgical management for this condition, along with a review of the literature. Case presentation We report a 62-year-old man with refractory chylothorax that occurred after esophagectomy caused by a hidden collateral branch of the injured thoracic duct with a rare positional relationship to the injury site. The chylous fluid from the unrevealed right-sided duct drained into the injured left-sided thoracic duct via the collateral branch opposite the injury on the side wall of the thoracic duct and continually leaked out through the injury. After ligation of the hidden branch, the patient was cured and discharged 2 wk later. Conclusion This is a rare case of distal partial duplication of the thoracic duct, and anatomical variation of the thoracic duct can still lead to chylothorax even if its main trunk has been ligated prophylactically. Care must be taken to adequately ligate both trunks in cases of distal duplication as there is shared proximal trunk, and hidden collateral branches should be carefully explored at the same time.

Triple negative breast cancer (TNBC) is one of the most malignant subtypes of breast cancer. Here, we report the construction of graphene nanoribbon (GNR)-based supramolecular ensembles with dual-receptor (mannose and αvβ3 integrin receptors) targeting function, denoted as GNR-Man/PRGD, for targeted photothermal treatment (PTT) of TNBC. The GNR-Man/PRGD ensembles were constructed through the solution-based self-assembly of mannose-grafted GNRs (GNR-Man) with a pyrene-tagged αvβ3 integrin ligand (PRGD). Enhanced PTT efficacies were achieved both in vitro and in vivo compared to that of the non-targeting equivalents. Tumor-bearing live mice were administered (tail vein) with GNR-Man/PRGD and then each mice group was subjected to PTT. Remarkably, GNR-Man/PRGD induced complete ablation of the solid tumors, and no tumor regrowth was observed over a period of 15 days. This study demonstrates a new and promising platform for the development of photothermal nanomaterials for targeted tumor therapy., Dual receptor-targeting supramolecular glycomaterials are constructed based on graphene nanoribbons for the targeted photothermal therapy of triple-negative breast cancer in vivo.

The ability to effectively detect bacterial infection in human tissues is important for the timely treatment of the infection. However, traditional techniques fail to visualize bacterial species adhered to host cells

Fluorescent probes have emerged as indispensable chemical tools to the field of chemical biology and medicine. The ability to detect intracellular species and monitor physiological processes has not only advanced our knowledge in biology but has provided new approaches towards disease diagnosis. In this review, we detail the design criteria and strategies for some recently reported fluorescent probes that can detect a wide range of biologically important species in cells and in vivo. In doing so, we highlight the importance of each biological species and their role in biological systems and for disease progression. We then discuss the current problems and challenges of existing technologies and provide our perspective on the future directions of the research area. Overall, we hope this review will provide inspiration for researchers and prove as useful guide for the development of the next generation of fluorescent probes.

The ester functionality is commonly seen in the areas of chemical biology and medicinal chemistry for the design of cell‐permeable active molecules. Ester‐based pro‐drug/pro‐sensor strategies are employed to mask polar functional groups (i. e. carboxylic acids) and improve the overall cell permeability of these functional molecules. However, their use as reactive units for sensing applications, including bacterial detection, has not been fully explored. Herein, we synthesised two TCF‐based fluorescent probes, TCF‐OAc and TCF‐OBu. As expected, both TCF‐OAc and TCF‐OBu demonstrated a significant fluorescence (22‐ and 43‐fold, respectively) and colorimetric response (yellow to purple) towards porcine liver esterase (PLE) with a limit of detection of 1.18 mU/mL and 0.45 mU/mL, respectively. With these results in hand, the ability of these probes to detect planktonic suspensions of gram‐positive Staphylococcus aureus (S. aureus) and gram‐negative Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli) were evaluated. Different fluorescence responses for gram‐positive and gram‐negative bacteria were observed between TCF‐OAc and TCF‐OBu. After 1 h incubation, TCF‐OAc proved more sensitive towards S. aureus, demonstrating a significant fluorescence “turn on” response (16‐fold); whereas, TCF‐OBu was more selective towards P. aeruginosa, with a 22‐fold increase in the fluorescence response observed. These results demonstrate the influence of the ester chain length on the selectivity for bacterial species.

Nanographenes (NGs) are exceptionally hydrophobic. They are insoluble in water, preventing the exploration and utilization of their photophysical properties under aqueous conditions. This work discloses an atomically precise water-soluble synthetic NG 1, featuring a 2 nm sp2 carbon skeleton appended with 12 branched triethylene glycol chains. It synergistically combines low critical solution temperature (LCST) behavior and a photothermal effect to create the first thermo- and photo-responsive atomically precise NG functioning in an aqueous solution. The LCST behavior can be attributed to a delicate balance of hydrophobic-hydrophilic interactions, providing a sensitive thermal response to changes over a temperature range of physiological interest (close to 37 °C). Moreover, 1 has considerable photothermal conversion capability, with irradiation of 1 in water by red or near infrared light increasing the solutions temperature to above the clouding point within seconds, leading to a reversible clear-to-turbid transition over many cycles without evident fatigue.

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.

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.

Reaction-based fluorescent-probes have proven successful for the visualisation of biological species in various cellular processes. Unfortunately, in order to tailor the design of a fluorescent probe to a specific application (i.e. organelle targeting, material and theranostic applications) often requires extensive synthetic efforts and the synthetic screening of a range of fluorophores to match the required synthetic needs. In this work, we have identified Pinkment-OH as a unique “plug-and-play” synthetic platform that can be used to develop a range of ONOO− responsive fluorescent probes for a variety of applications. These include theranostic-based applications and potential material-based/bioconjugation applications. The as prepared probes displayed an excellent sensitivity and selectivity for ONOO− over other ROS. In vitro studies using HeLa cells and RAW 264.7 macrophages demonstrated their ability to detect exogenously and endogenously produced ONOO−. Evaluation in an LPS-induced inflammation mouse model illustrated the ability to monitor ONOO− production in acute inflammation. Lastly, theranostic-based probes enabled the simultaneous evaluation of indomethacin-based therapeutic effects combined with the visualisation of an inflammation biomarker in RAW 264.7 cells., Pinkment, a resorufin based ONOO− selective and sensitive ‘plug and play’ fluorescence-based platform for in vitro and in vivo use, enables facile functionalisation for various imaging and theranostic applications.

With the development of nanomanufacturing methods, the manipulation of photons down to the nanoscale in silicon integrated optical chips has become a feasible and promising solution for next-generation data processing as electronic chips reach their limit. As an essential active device that generates photons for all other working photonic components, silicon lasers are the last barrier to achieve silicon integrated optical chips. Although optical gain in silicon nanocrystals (Si–NCs) was observed in 2000, the progress in realizing all-Si lasers has been very limited due to the inferior optical gain compared to traditional gain materials. In this paper, highly luminescent thin films of Si–NCs with a photoluminescence quantum yield of 57% are developed. The broadband photoluminescence covers the wavelength range from 650 to 900 nm, and wide-range optical gains are identified, indicating the feasibility of a tunable laser. Distributed feedback (DFB) all-Si lasers are fabricated using these thin films and pumped by femtosecond pulses. Various characteristic lasing behaviors are observed. Additionally, three different DFB grating periods are selected, and the lasing peak can be tuned by over 100 nm. The lasing thresholds range from 8.3 to 53.3 MW/cm2. The linewidths of lasing peaks are less than 2 nm.

Background Epidermal growth factor-containing fibulin-like extracellular matrix protein 2 (EFEMP2), also known as fibulin-4, MBP1 and UPH1, is an extracellular matrix protein associated with a variety of tumors. The purpose of this study was to investigate the prognostic value and the function of EFEMP2 in lung cancer. Methods The mRNA and protein expression of EFEMP2 in lung normal and cancer tissues, lung cancer cell lines (A549, H460, H1299 and H1650) and normal epithelial cell line BEAS-2B were evaluated by immunohistochemistry, RT-qPCR and Western blotting. The Public databases (Oncomine and Kaplan-Meier plotter) were used to investigate the prognostic value of EFEMP2 in lung cancer. RNA interference (RNAi) and overexpression transfection were performed to detect the effects of EFEMP2 up- or down-regulation on lung normal and cancer cell proliferation, invasion and metastasis in vitro and in vivo. Results EFEMP2 was lowly expressed in lung cancer tissues and cells, and its low expression was associated with malignant phenotype and poor prognosis of lung cancer. The same conclusion had been drawn from the Public databases. EFEMP2 overexpression significantly inhibited the invasion of lung cancer cells, hampered the process of EMT, and decreased the expression and activity of MMP2 and MMP9, while EFEMP2 knockdown remarkably enhanced the invasion of lung cancer cells, promoted EMT, and increased the expression and activity of MMP2 and MMP9. Conclusion The low expression of EFEMP2 was detected in lung cancer and was positively correlated with the poor prognosis of patients. EFEMP2 was a tumor suppressor gene that inhibited the progress of lung cancer, which suggested a new research objective for the future studies.

With the ever-increasing threat posed by the multi-drug resistance of bacteria, the development of non-antibiotic agents for the broad-spectrum eradication of clinically prevalent superbugs remains a global challenge. Here, we demonstrate the simple supramolecular self-assembly of structurally defined graphene nanoribbons (GNRs) with a cationic porphyrin (Pp4N) to afford unique one-dimensional wire-like GNR superstructures coated with Pp4N nanoparticles. This Pp4N/GNR nanocomposite displays excellent dual-modal properties with significant reactive-oxygen-species (ROS) production (in photodynamic therapy) and temperature elevation (in photothermal therapy) upon light irradiation at 660 and 808 nm, respectively. This combined approach proved synergistic, providing an impressive antimicrobial effect that led to the complete annihilation of a wide spectrum of Gram-positive, Gram-negative, and drug-resistant bacteria both in vitro and in vivo. The study also unveils the promise of GNRs as a new platform to develop dual-modal antimicrobial agents that are able to overcome antibiotic resistance.

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.