Recent advances in self-immobilizing fluorescent probes for in vivo imaging.

In situ precise detection of bioactive molecules with high sensitivity and spatiotemporal resolution is essential for studying physiological events and disease diagnosis. The utilization of versatile fluorescent probes in fluorescence imaging offers a powerful tool for in vivo imaging of biomarkers closely associated with pathological conditions. However, the dynamic behavior leading to rapid clearance of small molecule probes from regions of interest severely compromises their potential for precise imaging.

Cyclodextrin-Based Pickering Emulsion Significantly Increases 6-Gingerol Loading Through Two Different Mechanisms: Cyclodextrin Cavity and Pickering Core.

We previously found that host-guest interactions can drive gingerols (Gs) and cyclodextrins (CDs) together to form inclusion complexes (G/CD), which can further construct amphiphilic microcrystals and resultant Pickering emulsions through self-assembly. In this follow-up study, we explored the detailed formation processes and mechanisms of the 6-G/β-CD inclusion complex and the resultant Pickering emulsion. The influence of the 6-G/β-CD molar ratio on the structure, morphology, and loading capacity of the inclusion complex and resultant Pickering emulsion were investigated.

Ionizable lipid nanoparticles enhance lung delivery of gold nanoclusters for improving acute lung injury alleviation.

Acute lung injury (ALI) is one of the most common and highly prevailing respiratory system diseases. However, there is still a lack of effective specialized medicines for the treatment of ALI. Biocompatible gold nanoclusters (AuNCs) have shown great potential in alleviating ALI, but their lung-targeted delivery needs to be enhanced.

Hydrogen Sulfide (HS) Generated in the Colon Induces Neuropathic Pain by Activating Spinal NMDA Receptors in a Rodent Model of Chronic Constriction Injury.

Neuropathic pain (NP) imposes a significant burden on individuals, manifesting as nociceptive anaphylaxis, hypersensitivity, and spontaneous pain. Previous studies have shown that traumatic stress in the nervous system can lead to excessive production of hydrogen sulfide (HS) in the gut. As a toxic gas, it can damage the nervous system through the gut-brain axis.

NaHS alleviates neuropathic pain in mice by inhibiting IL-17-mediated dopamine (DA) neuron necroptosis in the VTA.

Background: Neuropathic pain (NP) constitutes a significant burden for individuals, manifesting as nociceptive anaphylaxis, hypersensitivity, and spontaneous pain. Previous research has suggested that the analgesic effects of NP are mediated by dopamine (DA) neurons in the ventral tegmental region (VTA) through projections to various brain regions. A decrease in VTA dopamine neurons following NP may contribute to prolonged pain.

β-galactosidase instructed in situ self-assembly fluorogenic probe for prolonged and accurate imaging of ovarian tumor.

Fluorescent probes are essential for optical imaging and have been extensively employed for precise cancer diagnosis studies. β-galactosidase (β-gal) serves as a primary biomarker for ovarian cancer and has been utilized to develop imaging probes for accurate tumor diagnosis. However, traditional small molecular probes have limitations in terms of rapid diffusion and metabolic clearance from the target lesion, resulting in a short imaging window and compromised tumor-to-background ratios (TBR).

Site-Specific Cascade-Activatable Fluorogenic Nanomicelles Enable Precision and Accuracy Imaging of Pulmonary Metastatic Tumor.

The precise localization of metastatic tumors with subtle growth is crucial for timely intervention and improvement of tumor prognosis but remains a paramount challenging. To date, site-specific activation of fluorogenic probes for single-stimulus-based diagnosis typically targets an occult molecular event in a complex biosystem with limited specificity. Herein, we propose a highly specific site-specific cascade-activated strategy to enhance detection accuracy, aiming to achieve the accurate detection of breast cancer (BC) lung metastasis in a cascade manner.

A probe for NIR-II imaging and multimodal analysis of early Alzheimer's disease by targeting CTGF.

To date, earlier diagnosis of Alzheimer's disease (AD) is still challenging. Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an upstream regulator of amyloid-beta (Aβ) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than Aβ plaque. Herein, we develop a peptide-coated gold nanocluster that specifically targets CTGF with high affinity (KD ~ 21.

Organ-Targeted Ionizable Lipid Nanoparticles Facilitate Sequence-Activated Fluorogenic Probe for Precise Imaging of Inflammatory Liver Disease.

Activatable near-infrared (NIR) fluorogenic probes offer a potent tool for real-time, in situ detection of hepatic biomarkers, significantly advancing the precision in diagnosing inflammatory liver disease (ILD). However, the limited distribution of small molecule fluorogenic probes in the liver and their rapid clearance impair the accuracy of fluorescence imaging and in ILD diagnosis. In this study, an effective utilization of ionizable lipid nanoparticles (iLNPs) is presented as liver-targeted carriers for efficient delivery of fluorogenic probes, aiming to overcome biodistribution barriers and achieve accurate detection of hepatic biomarkers.

An Efficient Strategy for Constructing Fluorescent Nanoprobes for Prolonged and Accurate Tumor Imaging.

Activatable near-infrared (NIR) fluorescent probes possess advantages of high selectivity, sensitivity, and deep imaging depth, holding great potential in the early diagnosis and prognosis assessment of tumors. However, small-molecule fluorescent probes are largely limited due to the rapid diffusion and metabolic clearance of activated fluorophores . Herein, we propose an efficient and reproducible novel strategy to construct activatable fluorescent nanoprobes through bioorthogonal reactions and the strong gold-sulfur (Au-S) interactions to achieve an enhanced permeability and retention (EPR) effect, thereby achieving prolonged and high-contrast tumor imaging .

Enhancing Liver Delivery of Gold Nanoclusters via Human Serum Albumin Encapsulation for Autoimmune Hepatitis Alleviation.

Peptide-protected gold nanoclusters (AuNCs), possessing exceptional biocompatibility and remarkable physicochemical properties, have demonstrated intrinsic pharmaceutical activity in immunomodulation, making them a highly attractive frontier in the field of nanomedicine exploration. Autoimmune hepatitis (AIH) is a serious autoimmune liver disease caused by the disruption of immune balance, for which effective treatment options are still lacking. In this study, we initially identified glutathione (GSH)-protected AuNCs as a promising nanodrug candidate for AIH alleviating in a Concanavalin A (Con A)-induced mice model.

Visual genetic typing of glioma using proximity-anchored in situ spectral coding amplification.

Gliomas are histologically and genetically heterogeneous tumors. However, classical histopathological typing often ignores the high heterogeneity of tumors and thus cannot meet the requirements of precise pathological diagnosis. Here, proximity-anchored in situ spectral coding amplification (ProxISCA) is proposed for multiplexed imaging of RNA mutations, enabling visual typing of brain gliomas with different pathological grades at the single-cell and tissue levels.

Potential Value of Probiotics on Lipid Profiles in Hyperlipidemia and Healthy Participants: Systematic Review and Meta-Analysis.

Objective: Many randomized controlled trials (RCTs) have reported the effect of probiotics on reducing plasma lipids with inconsistent results. An explicit systematic review and meta-analysis were conducted in this study to evaluate the effect of probiotics on the lipid profile of healthy and hyperlipidemia participants.

Methods: A comprehensive literature search of RCTs was conducted using PubMed, Embase, World Health Organization (WHO) Global Index Medicus, WHO clinical trial registry, and Clinicaltrials.

HS Alleviates Neuropathic Pain in Mice by Nrf2 Signaling Pathway Activation.

Neuropathic pain is a chronic pain caused by direct damage to the peripheral or central nervous system, characterized by hyperalgesia, allodynia, and spontaneous pain. Hydrogen sulfide (HS) therapy has been applied for neuropathic pain treatment, although the underlying mechanisms remain unknown. In this study, we sought to ascertain whether HS therapy could alleviate neuropathic pain in a model of chronic constriction injury (CCI) and, if so, the potential mechanism.

Liver-Targeted Near-Infrared Fluorescence/Photoacoustic Dual-Modal Probe for Real-Time Imaging of Hepatic Inflammation.

Early diagnosis of hepatic inflammation is the key to timely treatment and avoid the worsening of liver inflammation. Near-infrared fluorescence (NIRF) probes have high sensitivity but low spatial resolution in lesion imaging, while photoacoustic (PA) imaging has good spatial location information. Therefore, the development of a NIRF/PA dual-modal probe integrated with high sensitivity and spatial location feedback can achieve an accurate early diagnosis of hepatic inflammation.

Chemiluminescent Probes Based on 1,2-Dioxetane Structures For Bioimaging.

Chemiluminescent probes based on 1,2-dioxetane scaffold are one of the most sensitive imaging modalities for detecting disease-related biomarkers and can obtain more accurate biological information in cells and in vivo. Due to the elimination of external light excitation, the background autofluorescence problem in fluorescence technology can be effectively avoided, providing ultrahigh sensitivity and signal-to-noise ratio for various applications. In this review, we highlight a comprehensive but concise overview of activatable 1,2-dioxetane-based chemiluminescent probes by reporting significant advances in accurate detection and bioimaging.

Activatable fluorogenic probe for accurate imaging of ulcerative colitis hypoxia .

A simple but efficient fluorogenic probe is reported for accurate imaging of ulcerative colitis hypoxia detection. The hypoxia produced by ulcerative colitis can lead to the upregulation of nitroreductase (NTR). NB-NO2 provides a unique response to NTR, enabling accurate imaging of Dextran sulphate sodium (DSS)-induced ulcerative colitis .

Enzyme-activated near-infrared fluorogenic probe with high-efficiency intrahepatic targeting ability for visualization of drug-induced liver injury.

Hepatotoxicity is a serious problem faced by thousands of clinical drugs, and drug-induced liver injury (DILI) caused by chronic administration or overdose has become a major biosafety issue. However, the near-infrared (NIR) fluorescent probes currently used for liver injury detection still suffer from poor liver targeting ability and low sensitivity. Enzyme-activated fluorogenic probes with powerful targeting ability are the key to improving the imaging effect of liver injury.

Bioorthogonal chemistry in metal clusters: a general strategy for the construction of multifunctional probes for bioimaging in living cells and in vivo.

Multifunctional bioimaging probes based on metal clusters have multiple characteristics of metal clusters and functional conjugates, and their development has broad application prospects in the fields of biomedical imaging and tumor diagnosis. However, current bioconjugation methods on metal clusters are time-consuming and have low reaction efficiency, which hinders the construction of bioimaging probes with multifunctional components. Here, we report a concise and promising design strategy to realize the simple and efficient introduction of functional conjugates through bioorthogonal reactions based on azido-functionalized metal clusters.

Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy.

Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen (O), as well as the hypoxic microenvironment in the tumor tissue. Such problems have limited the application of PDT and appropriate solutions are highly demand.

Activatable Off-on Near-Infrared QCy7-based Fluorogenic Probes for Bioimaging.

The activatable off-on near-infrared QCy7-based fluorogenic probes have emerged as powerful modalities for detecting and monitoring biological analytes and understanding their biological processes in cells and organisms. The use of biomarker-activated QCy7-based probes enables simple synthesis, minimum photo-damage to biological samples, and minimum background interference from biological systems. In this minireview, we aim to provide a rigorous but concise overview of activatable QCy7-based fluorogenic probes by reporting the significant progress made in recent years.

Target identification of a macrocyclic hexaoxazole G-quadruplex ligand using post-target-binding visualization.

Macrocyclic hexaoxazoles (6OTDs) are G-quadruplex (G4) ligands, and some derivatives, such as L2H2-6OTD (1a) bearing two aminobutyl side chains, show cytotoxicity towards cancer cells. To identify the cellular target of 1a, we employed a post-target-binding strategy utilizing click reaction (Huisgen cyclization) between the azide-conjugated ligand L2H2-6OTD-Az (1b) and the cell-permeable dye CO-1 bearing a strained alkyne moiety and the BODIPY fluorophore under Cu-free conditions. We confirmed that introduction of the small azide group did not alter the physical or biological properties, including anti-cancer activity, of 1a, and we also demonstrated bias-free localization of CO-1.

Peptide and protein modified metal clusters for cancer diagnostics.

The biomedical features of metal clusters have been explored in tumor diagnostic applications in recent years. Peptide or protein protected metal clusters with low toxicity, ultra-small size and good biocompatibility are ideal bioanalytical tools, and exhibit better cancer diagnostic properties that have been attractive to oncologists. This perspective provides a rigorous but succinct overview of cancer diagnosis as a working concept for metal clusters by reporting the latest significant advances in the applications of metal clusters in tumor-related bioanalysis and diagnosis.