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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.

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.

Glycated haemoglobin (HbA1c) is a diagnostic biomarker for type 2 diabetes. Traditional analytical methods for haemoglobin (Hb) detection rely on chromatography, which requires significant instrumentation and is labour-intensive; consequently, miniaturized devices that can rapidly sense HbA1c are urgently required. With this research, we report on an aptamer-based sensor (aptasensor) for the rapid and selective electrochemical detection of HbA1c. Aptamers that specifically bind HbA1c and Hb were modified with a sulfhydryl and ferrocene group at the 3′ and 5′-end, respectively. The modified aptamers were coated through sulfhydryl-gold self-assembly onto screen printed electrodes, producing aptasensors with built in electroactivity. When haemoglobin was added to the electrodes, the current intensity of the ferrocene in the sensor system was reduced in a concentration-dependent manner as determined by differential pulse voltammetry. In addition, electrochemical impedance spectroscopy confirmed selective binding of the analytes to the aptamer-coated electrode. This research offers new insight into the development of portable electrochemical sensors for the detection of HbA1c

Neurodegenerative diseases (NDs), including chronic disease such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, and acute diseases like traumatic brain injury and ischemic stroke are characterized by progressive degeneration, brain tissue damage and loss of neurons, accompanied by behavioral and cognitive dysfunctions. So far, there are no complete cures for NDs; thus, early and timely diagnoses are essential and beneficial to patients' treatment. Magnetic resonance imaging (MRI) has become one of the advanced medical imaging techniques widely used in the clinical examination of NDs due to its non-invasive diagnostic value. In this review, research published in English in current decade from PubMed electronic database on the use of MRI to detect specific biomarkers of NDs was collected, summarized, and discussed, which provides valuable suggestions for the early diagnosis, prevention, and treatment of NDs in the clinic.

Biomacromolecular drugs have become an important class of therapeutic agents for the treatment of human diseases. Considering their high propensity for being degraded in the human body, the choice of an appropriate delivery system is key to ensure the therapeutic efficacy of biomacromolecular drugs in vivo. As an emerging class of supramolecular "host" materials, metal-organic frameworks (MOFs) exhibit advantages in terms of the tunability of pore size, encapsulation efficiency, controllable drug release, simplicity in surface functionalization and good biocompatibility. As a result, MOF-based host-guest systems have been extensively developed as a new class of flexible and powerful platform for the delivery of therapeutic biomacromolecules. In this review, we summarize current research progress in the synthesis of MOFs as delivery materials for a variety of biomacromolecules. Firstly, we briefly introduce the advances made in the use of biomacromolecular drugs for disease therapy and the types of commonly used clinical delivery systems. We then describe the advantages of using MOFs as delivery materials. Secondly, the strategies for the construction of MOF-encapsulated biomacromolecules (Biomacromolecules@MOFs) and the release mechanisms of the therapeutics are categorized. Thirdly, the application of MOFs to deliver different types of biomacromolecules (e.g., antigens/antibodies, enzymes, therapeutic proteins, DNA/RNA, polypeptides, and polysaccharides) for the treatment of various human diseases based on immunotherapy, gene therapy, starvation therapy and oxidation therapy is summarized. Finally, the remaining challenges and available opportunities for MOFs as drug delivery systems are outlined, which we anticipate will encourage additional research efforts directed towards developing Biomacromolecules@MOFs systems for biomedical applications.

Bacterial infection is a major threat to human health. However, many antibacterial agents currently used are severely limited due to drug-resistance, and the development of side effects. Herein, we have developed a non-antibiotic nanocomposite consisting of chitosan (ChS) coated silver nanoparticles (AgNPs) and graphene nanoribbon (GNR)-based nanowires for light-triggered eradication of bacteria. The presence of AgNP/ChS significantly enhanced the interactions of the GNR nanowires with Pseudomonas aeruginosa, a clinically common Gram-negative bacterium. Which enables the highly effective photothermal eradication of bacteria by GNR upon near-infrared light irradiation. The nanocomposite was shown to be applicable for the light-triggered eradication of bacterial biofilms and the inhibition of bacterial growth on medical patches used for abdominal-wall hernia surgery.

With this research, we have developed two long-wavelength theranostic probes (DCMT and DCMC) with aggregation-induced emission (AIE)-based properties for image-guided photodynamic therapy (PDT) of hepatoma cells. Introduction of a triphenylamine or carbazole group to a dicyanomethylene-4H-pyran dye with long-wavelength fluorescence emission produces the AIE-based probes, which were subsequently modified with triphenyl-phosphonium cation for actively targeting the mitochondria of hepatoma cells. Solution-based experiments show that the probes exhibit a mixed photophysical mechanism of twisted-intramolecular charge transfer and AIE at different aggregation states. The molecular aggregation of the probes also leads to an enhanced ability for oxygen photosensitization, suggesting their potential for PDT of cancer cells. Our subsequent cell-based assays show that the probes localize in the mitochondria of hepatoma cells and the use of light leads to cell death through the intracellular production of reactive oxygen species.