Advancements in Iron Oxide Nanoparticles for Multimodal Imaging and Tumor Theranostics.

The emergence of nanomedicine offers renewed promise in the diagnosis and treatment of diseases. Due to their unique physical and chemical properties, iron oxide nanoparticles (IONPs) exhibit widespread application in the diagnosis and treatment of various ailments, particularly tumors. IONPs have magnetic resonance (MR) T1/T2 imaging capabilities due to their different sizes. In addition, IONPs also have biocatalytic activity (nanozymes) and magnetocaloric effects. They are widely used in chemodynamic therapy (CDT), magnetic hyperthermia treatment (MHT), photodynamic therapy (PDT), and drug delivery. This review outlines the synthesis, modification, and biomedical applications of IONPs, emphasizing their role in enhancing diagnostic imaging (including single-mode and multimodal imaging) and their potential in cancer therapies (including chemotherapy, radiotherapy, CDT, and PDT). Furthermore, we briefly explore the challenges in the clinical application of IONPs, such as surface modification and protein adsorption, and put forward opinions on the clinical transformation of IONPs.

Graphene acid quantum dots: A highly active multifunctional carbon nano material that intervene in the trajectory towards neurodegeneration.

Carbon dots (CDs) are carbon nano materials (CNMs) that find use across several biological applications because of their water solubility, biocompatible nature, eco-friendliness, and ease of synthesis. Additionally, their physiochemical properties can be chemically tuned for further optimization towards specific applications. Here, we investigate the efficacy of C70-derived Graphene Acid Quantum Dots (GAQDs) in mitigating the transformation of soluble, monomeric Hen Egg-White Lysozyme (HEWL) to mature fibrils during its amyloidogenic trajectory. Our findings reveal that GAQDs exhibit dose-dependent inhibition of HEWL fibril formation (up to 70 % at 5 mg/mL) without affecting mitochondrial membrane potential or inducing apoptosis at the same density. Furthermore, GAQDs scavenged reactive oxygen species (ROS); achieving a 50 % reduction in ROS levels at a mere 100 µg/mL when exposed to a standard free radical generator. GAQDs were not only found to be biocompatible with a human neuroblastoma-derived SHSY-5Y cell line but also rescued the cells from rotenone-induced apoptosis. The GAQD-tolerance of SHSY-5Y cells coupled with their ability to restitute cells from rotenone-dependent apoptosis, when taken in conjunction with the biocompatibility data, indicate that GAQDs possess neuroprotective potential. The data position this class of CNMs as promising candidates for resolving aberrant cellular outputs that associate with the advent and progress of multifactorial neurodegenerative disorders including Parkinson's (PD) and Alzheimer's diseases (AD) wherein environmental causes are implicated (95 % etiology). The data suggest that GAQDs are a multifunctional carbon-based sustainable nano-platform at the intersection of nanotechnology and neuroprotection for advancing green chemistry-derived, sustainable healthcare solutions.

A novel NIR fluorescent probe for enhanced ß-galactosidase detection and tumor imaging in ovarian cancer models.

The advancement of biological imaging techniques critically depends on the development of novel near-infrared (NIR) fluorescent probes. In this study, we introduce a designed NIR fluorescent probe, NRO-ßgal, which exhibits a unique off-on response mechanism to ß-galactosidase (ß-gal). Emitting a fluorescence peak at a wavelength of 670 nm, NRO-ßgal showcases a significant Stokes shift of 85 nm, which is indicative of its efficient energy transfer and minimized background interference. The probe achieves a remarkably low in vitro detection limit of 0.2 U/L and demonstrates a rapid response within 10 min, thereby underscoring its exceptional sensitivity, selectivity, and operational swiftness. Such superior analytical performance broadens the horizon for its application in intricate biological imaging studies. To validate the practical utility of NRO-ßgal in bio-imaging, we employed ovarian cancer cell and mouse models, where the probe's efficacy in accurately delineating tumor cells was examined. The results affirm NRO-ßgal's capability to provide sharp, high-contrast images of tumor regions, thereby significantly enhancing the precision of surgical tumor resection. Furthermore, the probe's potential for real-time monitoring of enzymatic activity in living tissues underscores its utility as a powerful tool for diagnostics in oncology and beyond.

Enhancing resolution and contrast in fibre bundle-based fluorescence microscopy using generative adversarial network.

Fibre bundle (FB)-based endoscopes are indispensable in biology and medical science due to their minimally invasive nature. However, resolution and contrast for fluorescence imaging are limited due to characteristic features of the FBs, such as low numerical aperture (NA) and individual fibre core sizes. In this study, we improved the resolution and contrast of sample fluorescence images acquired using in-house fabricated high-NA FBs by utilising generative adversarial networks (GANs). In order to train our deep learning model, we built an FB-based multifocal structured illumination microscope (MSIM) based on a digital micromirror device (DMD) which improves the resolution and the contrast substantially compared to basic FB-based fluorescence microscopes. After network training, the GAN model, employing image-to-image translation techniques, effectively transformed wide-field images into high-resolution MSIM images without the need for any additional optical hardware. The results demonstrated that GAN-generated outputs significantly enhanced both contrast and resolution compared to the original wide-field images. These findings highlight the potential of GAN-based models trained using MSIM data to enhance resolution and contrast in wide-field imaging for fibre bundle-based fluorescence microscopy. Lay Description: Fibre bundle (FB) endoscopes are essential in biology and medicine but suffer from limited resolution and contrast for fluorescence imaging. Here we improved these limitations using high-NA FBs and generative adversarial networks (GANs). We trained a GAN model with data from an FB-based multifocal structured illumination microscope (MSIM) to enhance resolution and contrast without additional optical hardware. Results showed significant enhancement in contrast and resolution, showcasing the potential of GAN-based models for fibre bundle-based fluorescence microscopy.

A novel ratiometric fluorescent probe with high selectivity for lysosomal nitric oxide imaging.

Nitric oxide (NO) plays critical roles in both physiology and pathology, serving as a significant signaling molecule. Recent investigations have uncovered the pivotal role of lysosome as a critical organelle where intracellular NO exists and takes function. In this study, we developed a novel ratiometric fluorescent probe called XL-NO and modified it with a morpholine unit, which followed the intramolecular charge transfer (ICT) mechanism. The probe could detect lysosomal nitric oxide with high selectivity and sensitivity. The probe XL-NO contained a secondary amine moiety that could readily react with NO in lysosomes, leading to the formation of the N-nitrosation product. The N-nitroso structure enhanced the capability in push-pull electron, which obviously led to the change of fluorescence from 621 nm to 521 nm. In addition, XL-NO was discovered to have some evident advantages, such as significant ratiometric signal (I521/I621) change, strong anti-interference ability, good biocompatibility, and a low detection limit (LOD = 44.3 nM), which were crucial for the detection of lysosomal NO. To evaluate the practical application of XL-NO, NO imaging experiments were performed in both living cells and zebrafish. The results from these experiments confirmed the feasibility and reliability of XL-NO for exogenous/endogenous NO imaging and lysosome targeting.

A new carbazole based fluorescent probe with AIE characteristic for detecting and imaging hydrazine in living cells, mungbean sprouts, Arabidopsis thaliana, and practical samples.

In this study, we report a new carbazole-malononitrile fluorescent probe CBC with an interesting aggregation-induced emission (AIE) characteristic. Probe CBC could rapidly and selectively detect hydrazine (N2H4) in ～100% aqueous media, and also exhibit an exceedingly low detection limit of 6.3 nM for sensitively detecting N2H4. The sensing mechanism of CBC towards N2H4 has been well demonstrated through the spectra of 1H NMR, HRMS and FTIR. Interestingly, probe CBC was applied to visualize and detect gaseous and aqueous N2H4 with sensitive color changes. Importantly, probe CBC was applied to effectively detect N2H4 in practical samples such as soil, human serum, human urine, plants, foods and beverages, as well as sensitively sense and image N2H4 in biological systems including living mungbean sprouts, Arabidopsis thaliana, and HeLa cells.

Nanosensors Monitor Intracellular GSH Depletion: GSH Triggers Cu(II) for Tumor Imaging and Inhibition.

Glutathione (GSH) is the primary antioxidant in cells, and GSH consumption will break the redox balance in cells. Based on this, a method that uses high concentrations of GSH in the tumor microenvironment to trigger the redox reaction of Cu(II) to generate copper nanoprobes with fluorescence and tumor growth inhibition properties is proposed. The nanoprobe mainly exists in the form of Cu(I) and catalyzes the decomposition of hydrogen peroxide into hydroxyl radicals. At the same time, a simple and controllable carbon micro-nano electrode is used to construct a single-cell sensing platform, which enable the detection of glutathione content in single living cells after Cu(II) treatment, providing an excellent example for detecting single-cell biomolecules.

Ultrabright Green-Emissive Nanodots for Precise Biological Visualization.

Developing general methods to fabricate water-dispersible and biocompatible fluorescent probes will promote different biological visualization applications. Herein, we report a metal-facilitated method to fabricate ultrabright green-emissive nanodots via the one-step solvothermal treatment of rose bengal, ethanol, and various metal ions. These metal-doped nanodots show good water dispersity, ultrahigh photoluminescence quantum yields (PLQYs) (e.g., the PLQY of Fe-doped nanodots (FeNDs) was ∼97%), and low phototoxicity. Owing to the coordination effect of metal ions, the FeNDs realize glutathione detection with outstanding properties. Benefiting from the high endoplasmic reticulum (ER) affinity of the chloride group, the FeNDs can act as an ER tracker with long ER imaging capacity (FeNDs: >24 h; commercial ER tracker: ∼1 h) and superb photostability and can achieve tissue visualization in living Caenorhabditis elegans. The metal-doped nanodots represent a general nanodot preparation method and may shed new light on diverse biological visualization uses.

Progress of Mesoporous Silica Coated Gold Nanorods for Biological Imaging and Cancer Therapy.

For unique surface plasmon absorption and fluorescence characteristics, gold nanorods have been developed and widely employed in the biomedical field. However, limitations still exist due their low specific surface area, instability and tendency agglomerate in cytoplasm. Mesoporous silica materials have been broadly applied in field of catalysts, adsorbents, nanoreactors, and drug carriers due to its unique mesoporous structure, highly comparative surface area, good stability and biocompatibility. Therefore, coating gold nanorods with a dendritic mesopore channels can effectively prevent particle agglomeration, while increasing the specific surface area and drug loading efficiency. This review discusses the advancements of GNR@MSN in synthetic process, bio-imaging technique and tumor therapy. Additionally, the further application of GNR@MSN in imaging-guided treatment modalities is explored, while its promising superior application prospect is highlighted. Finally, the issues related to in vivo studies are critically examined for facilitating the transition of this promising nanoplatform into clinical trials.

Research progress of visualization methods and localization techniques of the cardiac conduction system / 中国胸心血管外科临床杂志

@#The cardiac conduction system (CCS) is a set of specialized myocardial pathways that spontaneously generate and conduct impulses transmitting throughout the heart, and causing the coordinated contractions of all parts of the heart. A comprehensive understanding of the anatomical characteristics of the CCS in the heart is the basis of studying cardiac electrophysiology and treating conduction-related diseases. It is also the key of avoiding damage to the CCS during open heart surgery. How to identify and locate the CCS has always been a hot topic in researches. Here, we review the histological imaging methods of the CCS and the specific molecular markers, as well as the exploration for localization and visualization of the CCS. We especially put emphasis on the clinical application prospects and the future development directions of non-destructive imaging technology and real-time localization methods of the CCS that have emerged in recent years.

Dual-channel versatile molecular sensing platform for individual and successive HClO and H2S detection: Applicable in toxic alerts of environmental samples and living organisms.

In this study, we have successfully developed a novel dual-response fluorescent probe, NACou, designed for the visual and quantitative detection of HClO/H2S in real water samples and liquid beverages by a thin-film sensing platform. Additionally, NACou demonstrated efficacy for sensing HClO/H2S in HeLa cells, plants and zebrafish through distinct fluorescent channels, yielding satisfactory results. NACou exhibited a multi-modal fluorescence response mechanism for detecting HClO and H2S with remarkable low detection limits of 27.8 nM and 34.4 nM, accompanied by outstanding fluorescent enhancement (209-fold and 148-fold, respectively). These advantages position NACou as a potent molecular tool for HClO and H2S sensing. The specific recognition performance of NACou towards HClO/H2S were confirmed through fluorescence spectroscopy, mass analysis and UV-vis spectroscopy. Importantly, the thin-film sensing platform with the visible fluorescence change can enable rapid assays for water quality and food safety monitoring, showcasing significant practical application value. Impressively, NACou has been employed in warning against liver injury induced by multiple drugs, allowing for the exploration of the pathogenesis and degree of drug-induced injury.

All-optical optoacoustic micro-tomography in reflection mode.

High-resolution optoacoustic imaging at depths beyond the optical diffusion limit is conventionally performed using a microscopy setup where a strongly focused ultrasound transducer samples the image object point-by-point. Although recent advancements in miniaturized ultrasound detectors enables one to achieve microscopic resolution with an unfocused detector in a tomographic configuration, such an approach requires illuminating the entire object, leading to an inefficient use of the optical power, and imposing a trans-illumination configuration that is limited to thin objects. We developed an optoacoustic micro-tomography system in an epi-illumination configuration, in which the illumination is scanned with the detector. The system is demonstrated in phantoms for imaging depths of up to 5 mm and in vivo for imaging the vasculature of a mouse ear. Although image-formation in optoacoustic tomography generally requires static illumination, our numerical simulations and experimental measurements show that this requirement is relaxed in practice due to light diffusion, which homogenizes the fluence in deep tissue layers.

Near-Infrared Bodipy-Based Molecular Rotors for ß-Amyloid Imaging In Vivo.

ß-amyloid (Aß) is one of the important biomarkers for diagnosing Alzheimer's disease (AD). Many near-infrared probes based on the donor-π-acceptor structure have been developed to detect Aß. Most reported Aß probes are based on the N,N-dimethylamino group as the ideal donor, which is a widely accepted binding unit. As such, the development of fluorescent probes with improved binding units to detect Aß is urgently required. Therefore, with this research three anchoring molecular rotor electron donors consisting of cyclic amines of different ring sizes are developed, namely five-membered ring (TPyr), six-membered ring (TPip), and seven-membered ring (THAI). These new anchored molecular rotors are connected to a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) and named TPyrBDP, TPipBDP, and THAIBDP. These probes exhibit high affinities (from 28 to 54 nm) for Aß1-42 aggregates. The six-membered ring dye TPipBDP exhibits the highest signal-to-noise (75.5-fold) and higher affinity (28.30 ± 5.94 nm). TPipBDP can cross the blood-brain barrier and exhibits higher fluorescence enhancement with APP/PS1 (AD) double transgenic (Tg) mice than with wild-type (WT) mice.

Recent development of surface-enhanced Raman scattering for biosensing.

Surface-Enhanced Raman Scattering (SERS) technology, as a powerful tool to identify molecular species by collecting molecular spectral signals at the single-molecule level, has achieved substantial progresses in the fields of environmental science, medical diagnosis, food safety, and biological analysis. As deepening research is delved into SERS sensing, more and more high-performance or multifunctional SERS substrate materials emerge, which are expected to push Raman sensing into more application fields. Especially in the field of biological analysis, intrinsic and extrinsic SERS sensing schemes have been widely used and explored due to their fast, sensitive and reliable advantages. Herein, recent developments of SERS substrates and their applications in biomolecular detection (SARS-CoV-2 virus, tumor etc.), biological imaging and pesticide detection are summarized. The SERS concepts (including its basic theory and sensing mechanism) and the important strategies (extending from nanomaterials with tunable shapes and nanostructures to surface bio-functionalization by modifying affinity groups or specific biomolecules) for improving SERS biosensing performance are comprehensively discussed. For data analysis and identification, the applications of machine learning methods and software acquisition sources in SERS biosensing and diagnosing are discussed in detail. In conclusion, the challenges and perspectives of SERS biosensing in the future are presented.

A p-toluenesulfonamide-modified benzo[h]chromene hydrazone: Fluorescent turn-on detection of hypochlorite and its application to imaging the endoplasmic reticula of living cells and zebrafishes.

Hypochlorite (ClO-) is a ROS that plays a crucial role in the immune system in the body. As the largest organelle in the cell, the endoplasmic reticulum (ER) manages various life activities. Thus, a simple hydrazone-based probe was designed, which provided a fast turn-on fluorescent response toward ClO-. With a terminal p-toluenesulfonamide group as the endoplasmic reticulum (ER)-specific site, probe 1 was mainly accumulated at ER of living cells, and could be used for imaging endogenous and exogenous HClO in cells and zebrafishes.

Multiscale denoising generative adversarial network for speckle reduction in optical coherence tomography images.

Purpose: Optical coherence tomography (OCT) is a noninvasive, high-resolution imaging modality capable of providing both cross-sectional and three-dimensional images of tissue microstructures. Owing to its low-coherence interferometry nature, however, OCT inevitably suffers from speckles, which diminish image quality and mitigate the precise disease diagnoses, and therefore, despeckling mechanisms are highly desired to alleviate the influences of speckles on OCT images. Approach: We propose a multiscale denoising generative adversarial network (MDGAN) for speckle reductions in OCT images. A cascade multiscale module is adopted as MDGAN basic block first to raise the network learning capability and take advantage of the multiscale context, and then a spatial attention mechanism is proposed to refine the denoised images. For enormous feature learning in OCT images, a deep back-projection layer is finally introduced to alternatively upscale and downscale the features map of MDGAN. Results: Experiments with two different OCT image datasets are conducted to verify the effectiveness of the proposed MDGAN scheme. Results compared those of the state-of-the-art existing methods show that MDGAN is able to improve both peak-single-to-noise ratio and signal-to-noise ratio by 3 dB at most, with its structural similarity index measurement and contrast-to-noise ratio being 1.4% and 1.3% lower than those of the best existing methods. Conclusions: Results demonstrate that MDGAN is effective and robust for OCT image speckle reductions and outperforms the best state-of-the-art denoising methods in different cases. It could help alleviate the influence of speckles in OCT images and improve OCT imaging-based diagnosis.

Imaging of a novel ratio γ-glutamyl transpeptidase fluorescent probe in living cells and biopsies.

Herein, a novel fluorescent probe, GTP, was developed for monitoring the GGT (γ-glutamyl transpeptidase) level in living cells and biopsies. It consisted of the typical recognition group γ-Glu (γ-Glutamylcysteine) and the fluorophore (E)-4-(4-aminostyryl)-1-methylpyridin-1-ium iodide. With a ratio response between the signal intensity at 560 nm and 500 nm (RI560/I500), it could be important complement for the turn-on ones. With the linear range of 0-50 U/L, the limit of detection was calculated as 0.23 µM. The detection system showed the strongest response near pH 7.4, and exhibited steady fluorescence signals for at least 48 h. With high selectivity, good anti-interference and low cytotoxicity, GTP was suitable for physiological applications. By monitoring the GGT level with the ratio values in the green and blue channels, the probe GTP could distinguish cancer cells from normal cells. Furthermore, in the mouse tissues and humanization tissue samples, the probe GTP could also recognize the tumor tissues from the normal ones.

Near-infrared ratiometric fluorescent strategy for butyrylcholinesterase activity and its application in the detection of pesticide residue in food samples and biological imaging.

Butyrylcholinesterase (BChE) is an essential esterase synthesized by the liver, and its level is considered as a vital index for health evaluation. Therefore, it is of great need to develop a highly sensitive and selective tool to monitor BChE activity, which remains a considerable challenge on account of its usage in complex biological systems. A near-infrared (NIR) fluorescent probe was elaborated in this work, employing cyanine backbone to provide the intrinsic NIR fluorescence and avoid interference from bioluminescence. There presented an intriguing structural transformation upon the sensing event to shrink the conjugation in this protocol, leading to an eye-catching fluorescence change from NIR (816 nm) to red (637 nm) region, which gave rise to the proposed ratiometric assay. After an overall investigation, this receptor was verified to be applicable in a wide bio-area with ratiometric pattern, including the cellular level and slice platform. It was worth mentioning that this receptor was also discovered to be capable of monitoring pesticide dichlorvos (DDVP) residue in food samples with high sensitivity and accuracy, with significant potential to be developed as an alternative candidate for monitoring environmental pollution.

Green synthesis and multifunctional applications of nitrogen-doped carbon quantum dots via one-step hydrothermal carbonization of Curcuma zedoaria.

Low-dimensional (<10 nm) semiconductor carbon quantum dots (CQDs) have been widely used in metal ion sensing and bioimaging. Here, we used the renewable resource Curcuma zedoaria as a carbon source and prepared green carbon quantum dots with good water solubility by a hydrothermal method without any chemical reagent. At different pH values (4-6) and high NaCl concentrations, the photoluminescence of the CQDs was very stable, which indicated that they were suitable for a wide range of applications even under harsh conditions. The CQDs exhibited fluorescence quenching in the presence of Fe3+ ions, indicating their application potential as fluorescence probes for the sensitive and selective detection of Fe3+ ions. The CQDs showed high photostability, low cytotoxicity, and good hemolytic activity, and were successfully applied to bioimaging experiments, i.e. multicolor cell imaging in L-02 (human normal hepatocytes) and CHL (Chinese hamster lung) cells with and without Fe3+, as well as wash-free labeling imaging of Staphylococcus aureus and Escherichia coli. The CQDs also showed good free radical scavenging activity and demonstrated a protective effect against photooxidative damage to L-02 cells. These results indicate that CQDs obtained from medicinal herb sources have multiple potential applications in the fields of sensing, bioimaging, and even disease diagnosis.

A dual-emission fluorescence probe for the detection of viscosity and hydrazine in environmental and biological samples.

The microenvironments of biological systems are associated with the pathology of organisms. This study, aimed to construct a hemicyanine-based probe (1), which can respond to mitochondrial viscosity and hydrazine (N2H4), for imaging application in living cells and zebrafish. The probe showed no fluorescence due to the intramolecular rotation in the solution; however, it exhibited a strong emission at 730 nm when the molecules were restricted to a high-viscosity environment. The addition of N2H4 caused an elimination reaction of the N-substituted group in the pyridinium part and further broke the CC bond to produce a highly fluorescent hydrazone. Also, the probe could selectively and quantitatively detect N2H4 via the fluorescence enhancement at 510 nm in a concentration range of 0 µM-140µM, with the limit of detection being 0.0485 µM. This probe may be used to study diseases related to N2H4 and viscosity changes in biological systems. Furthermore, the analysis methods based on probe 1 for N2H4 detection in soil, water, and air samples were successfully established.