Recent Advances in Fluorescent Probes for Cancer Biomarker Detection.

Many important biological species have been identified as cancer biomarkers and are gradually becoming reliable targets for early diagnosis and late therapeutic evaluation of cancer. However, accurate quantitative detection of cancer biomarkers remains challenging due to the complexity of biological systems and the diversity of cancer development. Fluorescent probes have been extensively utilized for identifying biological substances due to their notable benefits of being non-invasive, quickly responsive, highly sensitive and selective, allowing real-time visualization, and easily modifiable. This review critiques fluorescent probes used for detecting and imaging cancer biomarkers over the last five years. Focuses are made on the design strategies of small-molecule and nano-sized fluorescent probes, the construction methods of fluorescence sensing and imaging platforms, and their further applications in detection of multiple biomarkers, including enzymes, reactive oxygen species, reactive sulfur species, and microenvironments. This review aims to guide the design and development of excellent cancer diagnostic fluorescent probes, and promote the broad application of fluorescence analysis in early cancer diagnosis.

Probing Coordination Number of Single-Atom Catalysts by d-Band Center-Regulated Luminescence.

It is essential to probe the coordination number (CN) because it is a crucial factor to ensure the catalytic capability of single-atom catalysts (SACs). Currently, synchrotron X-ray absorption spectroscopy (XAS) is widely used to measure the CN. However, the scarcity of synchrotron X-ray source and complicated data analysis restrict its wide applications in determining the CN of SACs. In this contribution, we have developed a d-band center-regulated acetone cataluminescence (CTL) probe for a rapid screening of the CN of Pt-SACs. It is disclosed that the CN-triggered CTL is attributed to the fact that the increased CN could induce the downward shift of d-band center position, which assists the acetone adsorption and promotes the subsequent catalytic reaction. In addition, the universality of the proposed acetone-CTL probe is verified by determining the CN of Fe-SACs. This work has opened a new avenue for exploring an alternative to synchrotron XAS for the determination of CN of SACs and even conventional metal catalysts through d-band center-regulated CTL.

Molybdenum disulfide nanosheet induced reactive oxygen species for high-efficiency luminol chemiluminescence.

BACKGROUND: Luminol chemiluminescence (CL) sensing system remains an excellent candidate for application in bioanalysis due to its good water solubility. However, traditional luminol CL system usually requires the addition of oxidizing agents and sensitizers to obtain high efficiency for the improvement of detection sensitivity. Although numerous studies on the nanomaterial-enhanced luminol CL systems have been carried out, there is still great potential to develop inexpensive, readily available and easily handled catalysts to construct simple and effective CL platform for biomolecular sensing. RESULTS: Few-layered MoS2 nanosheets (NS) prepared by sonication-assisted exfoliation of commercially available bulk MoS2 were found to significantly enhance the CL of luminol‒dissolved oxygen in the absence of additional oxidants. The mechanism study demonstrated that exfoliated MoS2 NS could catalyze the decomposition of dissolved oxygen by virtue of its exposed active sites on the surface, generating increased reactive oxygen intermediates, which then oxidize luminol and produce intense CL emission. The proposed high-efficiency luminol CL system was then employed for the extremely sensitive identification of dopamine based on the quenching of CL by dopamine. The limit of detection (LOD) for dopamine can be as low as 2.07 nM. Besides, it also works well in the actual urine sample with good recoveries (99.6-100.6 %), confirming the practicability of the method. SIGNIFICANCE: As a new type of CL catalyst, MoS2 NS developed in this work are easy to obtain, simple to prepare and can be produced in large quantities, which lays a foundation for extending applicability of MoS2 NS in the CL field, and provides a new idea for developing simple and highly sensitive CL sensing system.

Vesicles as a Multifunctional Microenvironment for Electrochemiluminescence Signal Amplification.

Vesicles as a typical interface-rich microenvironment can promote the reaction rate and the intermediate stability, which are promising for introduction in electrochemiluminescence (ECL) signal amplification. In this work, a kind of multilamellar vesicle obtained from sodium bis(2-ethylhexyl) sulfosuccinate (AOT) was used to modify the electrode surface. The AOT vesicle-modified microenvironment could significantly enhance the ECL performances for the luminol/O2 system in a neutral medium. The mechanism study demonstrated that the nanoscale multilamellar vesicles could maintain the vesicle structure on the electrode surface, which substantially improved the electron transfer and reaction rate, luminescence efficiency of the excited-state 3-aminophthalate anion, and stability of the superoxide anion radical. Alternatively, such a multifunctional microenvironment was also able to enhance the ECL signals from the tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)32+)/tripropylamine (TPrA) system. Moreover, another dodecyl dimethyl(3-sulfopropyl) ammonium hydroxide inner salt (DSB)-based vesicle was constructed to further verify the versatility of the vesicle-modified microenvironment for ECL signal amplification. Our work not only provides a versatile microenvironment for improving the efficiency of various ECL systems but also offers new insights for the microenvironment construction using the ordered assemblies in ECL fields.

Recent Advances in Nanomaterial-Based Chemiluminescence Probes for Biosensing and Imaging of Reactive Oxygen Species.

Reactive oxygen species (ROS) play important roles in organisms and are closely related to various physiological and pathological processes. Due to the short lifetime and easy transformation of ROS, the determination of ROS content in biosystem has always been a challenging task. Chemiluminescence (CL) analysis has been widely used in the detection of ROS due to its advantages of high sensitivity, good selectivity and no background signal, among which nanomaterial-related CL probes are rapidly developing. In this review, the roles of nanomaterials in CL systems are summarized, mainly including their roles as catalysts, emitters, and carriers. The nanomaterial-based CL probes for biosensing and bioimaging of ROS developed in the past five years are reviewed. We expect that this review will provide guidance for the design and development of nanomaterial-based CL probes and facilitate the wider application of CL analysis in ROS sensing and imaging in biological systems.

Quantitative Measurement of Drug Release Dynamics within Targeted Organelles Using Förster Resonance Energy Transfer.

Measuring the release dynamics of drug molecules after their delivery to the target organelle is critical to improve therapeutic efficacy and reduce side effects. However, it remains challenging to quantitatively monitor subcellular drug release in real time. To address the knowledge gap, a novel gemini fluorescent surfactant capable of forming mitochondria-targeted and redox-responsive nanocarriers is designed. A quantitative Förster resonance energy transfer (FRET) platform is fabricated using this mitochondria-anchored fluorescent nanocarrier as a FRET donor and fluorescent drugs as a FRET acceptor. The FRET platform enables real-time measurement of drug release from organelle-targeted nanocarriers. Moreover, the obtained drug release dynamics can evaluate the duration of drug release at the subcellular level, which established a new quantitative method for organelle-targeted drug release. This quantitative FRET platform can compensate for the absent assessment of the targeted release performances of nanocarriers, offering in-depth understanding of the drug release behaviors at the subcellular targets.

Aggregation-induced emission-active micelles: synthesis, characterization, and applications.

Aggregation-induced emission (AIE)-active micelles are a type of fluorescent functional materials that exhibit enhanced emissions in the aggregated surfactant state. They have received significant interest due to their excellent fluorescence efficiency in the aggregated state, remarkable processability, and solubility. AIE-active micelles can be designed through the self-assembly of amphipathic AIE luminogens (AIEgens) and the encapsulation of non-emissive amphipathic molecules in AIEgens. Currently, a wide range of AIE-active micelles have been constructed, with a significant increase in research interest in this area. A series of advanced techniques has been used to characterize AIE-active micelles, such as cryogenic-electron microscopy (Cryo-EM) and confocal laser scanning microscopy (CLSM). This review provides an overview of the synthesis, characterization, and applications of AIE-active micelles, especially their applications in cell and in vivo imaging, biological and organic compound sensors, anticancer drugs, gene delivery, chemotherapy, photodynamic therapy, and photocatalytic reactions, with a focus on the most recent developments. Based on the synergistic effect of micelles and AIE, it is anticipated that this review will guide the development of innovative and fascinating AIE-active micelle materials with exciting architectures and functions in the future.

Real-Time Imaging of Stress in Single Spherulites and Its Relaxation at the Single-Particle Level in Semicrystalline Polymers.

Crystallization-induced microscopic stress and its relaxation play a vital role in understanding crystallization behavior and mechanism. However, the real-time measurements for stress and its relaxation seem to be an unachievable task due to difficulties in simultaneous labeling, spatiotemporal discrimination, and continuous quantification. We designed a micron-sized fluorescent probe, whose fluorescence can respond to stress-induced environmental rigidity and whose three-dimensional (3D) flow can respond to stress relaxation. Using the as-prepared fluorescent probe, we established a versatile strategy to realize the real-time 3D imaging of stress and its relaxation in the crystallization process. The rigidity-responsive fluorescence clearly indicated the stress, while the 3D flow movement could quantify the stress relaxation. It is revealed that stress in spherulites increased dramatically as a result of the suppression of stress relaxation in polymer melts. The developed method provides a novel avenue to simultaneously detect stress and its relaxation in various semicrystalline polymers at the single-particle level. This success would achieve the microscopic ways to guide the development of advanced crystallization-dependent materials.

Determination of the critical micelle concentration of surfactants using fluorescence strategies.

The increasing importance of surfactants in various fields has led to growing interest in the comprehensive characterization of surfactants. The critical micelle concentration (CMC), the most fundamental property of surfactants, is a parameter that must be measured. In particular, with the continuous expansion of the molecular structure of surfactants, numerous novel amphiphilic molecules have been developed that are capable of forming ordered aggregates in various solvent systems. Fluorescence spectroscopy, based on the differences in fluorescence intensity and wavelength of the fluorescent probe in the solvent phase and micellar phase, can sensitively detect the CMC of surfactants. This review aims to summarize the various fluorescence methods used to determine the CMC, including aggregation-induced emission (AIE), excimer formation, intramolecular charge transfer (ICT), and other miscellaneous strategies. The difficulties and limitations in the CMC determination process are also described. Further suggestions are provided to guide the existing fluorescence probes and the corresponding fluorescence methods to detect critical aggregation concentrations of amphiphilic molecules.

Advances in nanosensors for cardiovascular disease detection.

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality around the world. The physiological or pathological processes of CVDs can be well indicated by timely and accurate diagnosis of relevant biomarkers and function parameters. Nanosensors integrating the advantages of nanomaterials and sensing platforms have shown good potential for rapid diagnosis of CVDs, especially for early prediction. In this review, recent advances in nanosensors for the detection of CVDs are summarized, including electrochemical, optical, pressure, and paper-based nanosensors. Design strategies for different nanosensors and the corresponding sensing nanomaterials, mechanisms, and properties are briefly discussed. This review also offered a preliminary analysis of the obstacles and prospects for using nanosensors to diagnose CVDs.

Cationic AIEgen micelle-improved chemiluminescent H2O2 assay by integrating reactant approach and CRET.

The enhancement of chemiluminescence (CL) intensity is significant in the development of chemiluminescent detection systems with improved sensitivity. In this study, a cationic surfactant with an intrinsic aggregation-induced emission emitter (AIEgen) has been applied to boost the CL signal of the horseradish peroxidase-luminol-H2O2 system. The formed cationic AIEgen micelles enhance the CL signal in two ways: the electrostatic attraction-mediated enrichment and approach of reactants and the high CRET efficiency between excited luminol radicals and AIEgen in the surfactant backbone. As a result, strong CL intensity is produced. Rapid and sensitive H2O2 detection is realized through the proposed cationic AIEgen micelle-containing chemiluminescent system with a limit of detection of 100 nM. The favourable selectivity over other possible interferents including metal ions and anions is due to the specific chemical reaction. Practical H2O2 analysis of thawing water samples with high accuracy using the proposed chemiluminescent platform is realized and is consistent with standard methods.

Ag-O-Co Interface Modulation-Amplified Luminol Cathodic Electrogenerated Chemiluminescence.

It remains a great challenge to develop effective strategies for improving the weak cathodic electrogenerated chemiluminescence (ECL) of the luminol-dissolved O2 system. Interface modulation between metal and supports is an attractive strategy to improve oxygen reduction reaction (ORR) activity. Therefore, the design of electrocatalysts via interface modulation would provide new opportunities for the ECL amplification involving reactive oxygen species (ROSs). Herein, we have fabricated an Ag single-atom catalyst with an oxygen-bridged interface (Ag-O-Co) through the electrodeposition of Ag on a CoAl layered double hydroxide (LDH) modified indium tin oxide (ITO) electrode (Ags/LDH/ITO). Interestingly, it was found that the cathodic ECL intensity of the luminol-dissolved O2 system at the Ags/LDH/ITO electrode was extraordinarily enhanced in comparison with those at bare ITO and other Ag nanoparticle-based electrodes. The enhanced ECL performances of the Ags/LDH/ITO electrode were attributed to the increasing amounts of ROSs by electrocatalytic ORR in the Ag-O-Co interface. The electron redistribution of Ag and Co bimetallic sites could accelerate electron transfer, promote the adsorption of O2, and sufficiently activate O2 through a four-electron reaction pathway. Finally, the luminol cathodic ECL intensity was greatly improved. Our findings can provide inspiration for revealing the interface effects between metal and supports, and open up a new avenue to improve the luminol cathodic ECL.

Advances in intelligent-responsive nanocarriers for cancer therapy.

With the rapid development of nanotechnology, strategies related to nanomedicine have been used to overcome the shortcomings of traditional chemotherapy drugs, thereby demonstrating significant potential for innovative drug delivery. Nanomaterials play an increasingly important role in cancer immunotherapy. Stimuli-responsive nanomaterials enable the precise control of drug release through exposure to specific stimuli and exhibit excellent specificity in response to various stimuli. Immunomodulators carried by nanomaterials can also effectively regulate the immune system and significantly improve their therapeutic effect on cancer. In recent years, stimuli-responsive nanomaterials have evolved rapidly from single stimuli-responsive systems to multi-stimuli-responsive systems. This review focuses on recent advances in the design and applications of stimuli-responsive nanomaterials, including exogenous and endogenous responsive nanoscale drug delivery systems, which show extraordinary potential in intelligent drug delivery for multimodal cancer diagnosis and treatment. Ultimately, the opportunities and challenges in the development of intelligent responsive nanomaterials are briefly discussed according to recent advances in multi-stimuli-responsive systems.

Rapid Discrimination of Adsorbed Oxygen and Lattice Oxygen in Catalysts by the Cataluminescence Method.

Adsorbed oxygen and lattice oxygen are crucial parameters for catalyst characterization and catalytic oxidation mechanism. Therefore, rapid discrimination of adsorbed oxygen and lattice oxygen is highly desired. Herein, a direct correlation between cataluminescence (CTL) kinetic curve and oxygen species was discovered. The adsorbed oxygen-catalyzed CTL only lasted for a few minutes, whereas the lattice oxygen-catalyzed CTL could exhibit hours of continuous luminescence. The long-term CTL was attributed to the slow migration of lattice oxygen in a slow and continuous catalytic oxidation reaction. In addition to the discrimination between the adsorbed oxygen and lattice oxygen by the CTL kinetic processes, the corresponding CTL intensity was positively proportional to their amounts. Accordingly, the developed catalytic oxidation-related CTL can be used as an indicator for rapid discrimination and determination of adsorbed oxygen and lattice oxygen in catalysts. Oxygen species detected by the proposed CTL method not only matched well with those obtained by conventional X-ray photoelectron spectroscopy and O2-temperature programmed methods but also offered some distinguished advantages, such as convenient operation, fast response, and low cost. It can be expected that the established oxygen-responsive CTL probe has great potential in distinguishing adsorbed oxygen and lattice oxygen in various catalysts.

Charge Neutralization Strategy to Construct Salt-Tolerant and Cell-Permeable Nanoprobes: Application in Ratiometric Sensing and Imaging of Intracellular pH.

Intracellular pH homeostasis is essential for the survival and function of biological cells. Negatively charged molecular probes, such as pyranine (HPTS), tend to exhibit poor salt tolerance and unsatisfactory cell permeability, limiting their widespread use in intracellular assays. Herein, we explored a charge neutralization strategy using multicharged cationic nanocarriers for an efficient and stable assembly with the pH-sensitive HPTS. Through immobilization and neutralization with poly(allylamine hydrochloride)-stabilized red-emitting gold nanoclusters (PAH-AuNCs), the resulting nanoprobes (HPTS-PAH-AuNCs) offered improved salt tolerance, satisfactory cell permeability, and dual-emission properties. The fluorescence ratio exhibited a linear response over the pH range of 3.0-9.0. Moreover, the proposed HPTS-PAH-AuNCs were successfully applied to determine and visualize lysosomal pH variations in living cells, which indicated great potential for biosensing and bioimaging applications in living systems. Benefiting from the charge neutralization strategy, various types of probes can be expected to achieve broader analytical applications.

Recent Advances in Fluorescence Imaging of Pulmonary Fibrosis in Animal Models.

Pulmonary fibrosis (PF) is a lung disease that may cause impaired gas exchange and respiratory failure while being difficult to treat. Rapid, sensitive, and accurate detection of lung tissue and cell changes is essential for the effective diagnosis and treatment of PF. Currently, the commonly-used high-resolution computed tomography (HRCT) imaging has been challenging to distinguish early PF from other pathological processes in the lung structure. Magnetic resonance imaging (MRI) using hyperpolarized gases is hampered by the higher cost to become a routine diagnostic tool. As a result, the development of new PF imaging technologies may be a promising solution. Here, we summarize and discuss recent advances in fluorescence imaging as a talented optical technique for the diagnosis and evaluation of PF, including collagen imaging, oxidative stress, inflammation, and PF-related biomarkers. The design strategies of the probes for fluorescence imaging (including multimodal imaging) of PF are briefly described, which can provide new ideas for the future PF-related imaging research. It is hoped that this review will promote the translation of fluorescence imaging into a clinically usable assay in PF.

Recent Advances in Fluorescence Imaging of Traumatic Brain Injury in Animal Models.

Traumatic brain injury (TBI) is one of the top three specific neurological disorders, requiring reliable, rapid, and sensitive imaging of brain vessels, tissues, and cells for effective diagnosis and treatment. Although the use of medical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) for the TBI detection is well established, the exploration of novel TBI imaging techniques is of great interest. In this review, recent advances in fluorescence imaging for the diagnosis and evaluation of TBI are summarized and discussed in three sections: imaging of cerebral vessels, imaging of brain tissues and cells, and imaging of TBI-related biomarkers. Design strategies for probes and labels used in TBI fluorescence imaging are also described in detail to inspire broader applications. Moreover, the multimodal TBI imaging platforms combining MRI and fluorescence imaging are also briefly introduced. It is hoped that this review will promote more studies on TBI fluorescence imaging, and enable its use for clinical diagnosis as early as possible, helping TBI patients get better treatment and rehabilitation.

Disordered Assembly of Donors and Acceptors on Layered Double Hydroxides for High-Efficiency Chemiluminescence Resonance Energy Transfer.

High-efficiency chemiluminescence (CL) resonance energy transfer (CRET) can be obtained by shortening the donor-acceptor distance and/or improving the luminescence efficiency of CRET acceptors. However, careful design and stringent experimental conditions are usually required for the ordered assembly of CRET acceptors on support materials to avoid aggregation-caused quenching problems. In this work, an aggregation-induced emission (AIE)-active fluorophore was disorderly adsorbed on the surface of layered double hydroxides (LDHs), which could exhibit high-efficiency luminescence. On the other hand, the positively charged LDHs can further adsorb peroxynitrite (ONOO-) on the surface of LDHs. Therefore, the LDH-supported AIE fluorophore could dramatically amplify weak CL signals from ONOO- donors as a result of ultra-high CRET efficiency by coupling the shorter donor-acceptor distance with efficient CRET acceptors. The proposed CL system has been successfully applied for the detection of NaNO2 in the concentration range from 1.0 to 100 µM with a detection limit as low as 0.5 µM. Satisfactory recoveries (98-106%) and good accuracy were achieved for sausage samples. Our success will open new avenues for the convenient design of high-efficiency CRET systems.

Chemiluminescence Resonance Energy Transfer Efficiency and Donor-Acceptor Distance: from Qualitative to Quantitative.

Since its birth in 1967, the utilization of chemiluminescence resonance energy transfer (CRET) has made substantial progress in a variety of fields for its unique features. However, the quantitative relationship between CRET efficiency and donor-acceptor distance has not yet been determined owing to the difficulty in designing the variable lengths between chemiluminescent donors and acceptors. Herein, we synthesized three kinds of tetraphenylethene (TPE)-anchored cationic surfactants with aggregation-induced emission (AIE) characteristics. For the first time, it is quantitatively demonstrated that the CRET efficiency is inversely proportional to the sixth power of distance between luminol donors and TPE acceptors. The details disclosed in this contribute have provided the solid evidence that CRET follows Förster resonance theory. Our strategy would build a promising platform to control donor-acceptor distance, allowing to the interdisciplinary applications of CRET.

The Promise of Aggregation-Induced Emission Luminogens for Detecting COVID-19.

The long-term pandemic of coronavirus disease 2019 (COVID-19) requires sensitive and accurate diagnostic assays to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and SARS-CoV-2 antibodies in infected individuals. Currently, RNA of SARS-CoV-2 virus is mainly detected by reverse transcription-polymerase chain reaction (RT-PCR)-based nucleic acid assays, while SARS-CoV-2 antigen and antibody are identified by immunological assays. Both nucleic acid assays and immunological assays rely on the luminescence signals of specific luminescence probes for qualitative and quantitative detection. The exploration of novel luminescence probes will play a crucial role in improving the detection sensitivity of the assays. As innate probes, aggregation-induced emission (AIE) luminogens (AIEgens) exhibit negligible luminescence in the free state but enhanced luminescence in the aggregated or restricted states. Moreover, AIEgen-based nanoparticles (AIE dots) offer efficient luminescence, good biocompatibility and water solubility, and superior photostability. Both AIEgens and AIE dots have been widely used for high-performance detection of biomolecules and small molecules, chemical/biological imaging, and medical therapeutics. In this review, the availability of AIEgens and AIE dots in nucleic acid assays and immunological assays are enumerated and discussed. By building a bridge between AIE materials and COVID-19, we hope to inspire researchers to use AIE materials as a powerful weapon against COVID-19.