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.

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.

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 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.

Design of ratiometric monoaromatic fluorescence probe via modulating intramolecular hydrogen bonding: A case study of alkaline phosphatase sensing.

Monoaromatic molecules are a category of molecules containing a single aromatic ring which generally emit light in the ultraviolet (UV) region. Despite their facile preparation, the UV emission greatly limits their application as organic probes. In this study, we developed a general method to red shift the emission of monoaromatic molecules. Significant fluorescence red-shift (∼100 nm per intramolecular hydrogen bonding) can be achieved by introducing intramolecular hydrogen bonding units to benzene, a typical monoaromatic molecule. Upon increasing the number of hydrogen bonding units on the benzene ring, UV, blue, and green emissions are screened, which are switchable by simply breaking/restoration the intramolecular hydrogen bonding. As a demonstration, with the breaking of one intramolecular H-bonding, the green emission (λemmax = 533 nm) of 2,5-dihydroxyterephthalic acid (DHTA) changed to cyan (λemmax = 463 nm) upon the formation of its phosphorylated form (denoted as PDHTA), which, in the presence of alkaline phosphatase (ALP), hydrolyzed and recovered the green emission. By taking advantage of the switchable emission colors, ratiometric in vitro and endogenous ALP sensing was achieved. This general approach offers a great promise to develop organic probes with tunable emissions for fluorescence analysis and imaging by different intramolecular hydrogen bonding.

Recent advances of plasmonic nanoparticle-based optical analysis in homogeneous solution and at the single-nanoparticle level.

Plasmonic nanoparticles with special localized surface plasmon resonance (LSPR) characters have been widely applied for optical sensing of various targets. With the combination of single nanoparticle imaging techniques, dynamic information of reactions and biological processes is obtained, facilitating the deep understanding of their principle and design of outstanding nanomaterials. In this review, we summarize the recently adopted optical analysis of diverse analytes based on plasmonic nanoparticles both in homogeneous solution and at the single-nanoparticle level. A brief introduction of LSPR is first discussed. Colorimetric and fluorimetric homogeneous detection examples by using different sensing mechanisms and strategies are provided. Single plasmonic nanoparticle-based analysis is concluded in two aspects: visualization of chemical reactions and understanding of biological processes. The basic sensing mechanisms and performances of these systems are introduced. Finally, this review highlights the challenges and future trend of plasmonic nanoparticle-based optical analysis systems.

A Eu3+-inspired fluorescent carbon nanodot probe for the sensitive visualization of anthrax biomarker by integrating EDTA chelation.

The rapid and sensitive visualization of 2,6-dipicolinic acid (DPA, a unique anthrax biomarker) is essential to prevent anthrax disease or biological terrorist attack. In this study, a Eu3+-labeled ethylenediaminetetraacetic acid loaded hyperbranched polyethyleneimine carbon nanodot (hPEI-CD-EDTA-Eu3+) nanoprobe has been proposed for the ratiometric DPA detection. The sensing mechanism is based on the rapid DPA-Eu3+ chelation within 30 s and subsequent enhanced fluorescence emission through the antenna effect. With the introduction of EDTA chelating unit, the resulted fluorescence of Eu3+-complex is greatly enhanced, which endows sensitive DPA perception. By employing hPEI-CD as the internal reference, ratiometric DPA sensing is realized with a good linearity in the concentration range from 1.0 to 100 nM, with a limit of detection of 190 pM (S/N = 3). The specific chelation affinity between Eu3+ and DPA provides satisfying selectivity over other amino acids and ions. Using nanoprobe-loaded polyvinylidene fluoride paper as the analytical device, point-of-care DPA visualization is achieved. Furthermore, the practical application of designed paper device is validated by the visual detection of metabolic DPA-release from Bacillus subtilis spores.

Tris-Co(II)-H2O2 System-Mediated Durative Hydroxyl Radical Generation for Efficient Anionic Azo Dye Degradation by Integrating Electrostatic Attraction.

The development of simple Fenton/Fenton-like systems with durative hydroxyl radical (•OH) generation characteristics is significant to rapid organic pollutant degradation and cost-effective water treatment. In this study, a tris(hydroxymethyl)aminomethane (Tris)-incorporated Co(II)-H2O2 Fenton-like system has been successfully constructed for efficient Sunset Yellow (SY, a typical anionic azo dye) degradation under alkaline conditions. The mechanism of the enhanced degradation consists of two parts: first, the Tris-Co(II) complex triggers the durative generation of highly oxidized hydroxyl radicals; second, electrostatic attraction between SY and the Tris-Co(II) complex shortens the radical-SY interaction time and facilitates the degradation of SY. With the introduction of Tris to this proposed system, the decolorization rate of SY can be increased from 37.0 to 98.0% after 50 min and efficient SY degradation with a high total organic carbon removal efficiency (>59.0%) is achieved under a wide initial pH from 8.7 to 12.0. Moreover, the universality of the designed system for anionic azo dye degradation is verified with reactive red and congo red.