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A Novel Chemiluminescent Probe Based on 1,2-Dioxetane Scaffold for Imaging Cysteine in Living Mice
摘要： A novel chemiluminescent probe for detection of cysteine (Cys) from other biothiols has been reported by utilizing the excellent chemiluminescent Schaap’s adamantylidene-dioxetane scaffold. After careful assessment, the probe CL-Cys could detect Cys with high sensitivity and total light photons increased with 28-fold after the probe was treated with Cys, with the detection limit of 7.5 x 10-8 M. Finally, CL-Cys was further utilized to the chemiluminescent imaging of endogenous Cys in living mouse. In general, this probe has a remarkable ability of detecting Cys, which provides a valuable method for interrogation the Cys roles in more biological and pathological processes.
关键词： Chemiluminescent probe,1,Cysteine,2-dioxetane,Chemiluminescent imaging,In vivo imaging.,Living animal
更新于2025-09-23 15:23:52
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In vivo multiphoton microscopy detects longitudinal metabolic changes associated with delayed skin wound healing
摘要： Chronic wounds are difficult to diagnose and characterize due to a lack of quantitative biomarkers. Label-free multiphoton microscopy has emerged as a useful imaging modality capable of quantifying changes in cellular metabolism using an optical redox ratio of FAD/(NADH+FAD) autofluorescence. However, the utility of an optical redox ratio for long-term in vivo monitoring of tissue metabolism has not been robustly evaluated. In this study, we demonstrate how multiphoton microscopy can be used to monitor changes in the metabolism of individual full-thickness skin wounds in vivo. 3D optical redox ratio maps and NADH fluorescence lifetime images identify differences between diabetic and control mice during the re-epithelialization of wounds. These metabolic changes are associated with a transient increase in keratinocyte proliferation at the wound edge. Our study demonstrates that high-resolution, non-invasive autofluorescence imaging can be performed in vivo and that optical redox ratios can serve as quantitative optical biomarkers of impaired wound healing.
关键词： metabolism,optical redox ratio,autofluorescence,multiphoton microscopy,in vivo imaging,diabetes,FAD,NADH,wound healing
更新于2025-09-23 15:23:52
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Multispectral optoacoustic tomography (MSOT) for imaging the particle size-dependent intratumoral distribution of polymeric micelles
摘要： Purpose: This study proposes the utilization of multispectral optoacoustic tomography (MSOT) to investigate the intratumoral distribution of polymeric micelles and effect of size on the biodistribution and antitumor efficacy (ATE). Materials and methods: Docetaxel and/or optoacoustic agent-loaded polymeric micelles (with diameters of 22, 48, and 124 nm) were prepared using amphiphilic block copolymers poly (ethylene glycol) methyl ether-block-poly (D,L lactide) (PEG2000–PDLLAx). Subcutaneous 4T1 tumor-bearing mice were monitored with MSOT imaging and IVIS? Spectrum in vivo live imaging after tail vein injection of micelles. The in vivo results and ex vivo confocal imaging results were then compared. Next, ATE of the three micelles was found and compared. Results: We found that MSOT imaging offers spatiotemporal and quantitative information on intratumoral distribution of micelles in living animals. All the polymeric micelles rapidly extravasated into tumor site after intravenous injection, but only the 22-nm micelle preferred to distribute into the inner tumor tissues, leading to a superior ATE than that of 48- and 124-nm micelles. Conclusion: This study demonstrated that MSOT is theranostically a powerful imaging modality, offering quantitative information on size-dependent spatiotemporal distribution patterns after the extravasation of nanomedicine from tumor blood vessels.
关键词： intratumoral distribution,MSOT,multispectral optoacoustic tomography,in vivo imaging,tumor model,particle size,polymeric micelle
更新于2025-09-23 15:23:52
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Rational Design of Near-Infrared AIE-Active Probes: In Situ Mapping of Amyloid-β Plaques with Ultra-Sensitivity and High-Fidelity
摘要： High-fidelity mapping of amyloid-β (Aβ) plaques is critical for the early detection of Alzheimer’s disease. However, in vivo probing of Aβ plaques by commercially available Thioflavin derivatives (ThT or ThS) has proven to be extremely limited, as evident by the restriction of enrichment quenching effect, low signal-to-noise (S/N) ratio and poor blood-brain barrier (BBB) penetrability. Herein, we demonstrate a rational design strategy of near-infrared (NIR) aggregation-induced emission (AIE)-active probes for Aβ plaques, through introducing lipophilic π-conjugated thiophene-bridge for extending to NIR wavelength with enhancement of BBB penetrability, and tuning the substituted position of sulfonate group for guaranteeing specific hydrophilicity to keep fluorescence-off state before binding to Aβ deposition. Probe QM-FN-SO3 has well settled the AIE dilemma between lipophilic requirement for longer emission and aggregation behavior from water to protein fibrillogenesis, thus making a breakthrough in high-fidelity feedback on in vivo detection of Aβ plaques with remarkable binding affinity, and serving as an efficient alternative to the commercial probe ThT or ThS.
关键词： Fluorescent probe,In vivo imaging,Aggregation-induced emission,Amyloid-β plaques,Near-infrared
更新于2025-09-23 15:23:52
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Visualizing Interactions of Circulating Tumor Cell and Dendritic Cell in the Blood Circulation Using In Vivo Imaging Flow Cytometry
摘要： Objective: Visualizing cell interactions in blood circulation is of great importance in studies of anticancer immunotherapy or drugs. However, the lack of a suitable imaging system hampers progress in this field. Methods: In this work, we built a dual-channel in vivo imaging flow cytometer to visualize the interactions of circulating tumor cells (CTCs) and dendritic cells (DCs) simultaneously in the bloodstream. Two artificial neural networks were trained to identify blood vessels and cells in the acquired images. Results and Conclusion: Using this technique, single CTCs and CTC clusters were readily distinguished by their morphology. Interactions of CTCs and DCs were identified, while their moving velocities were analyzed. The CTC-DC clusters moved at a slower velocity than that of single CTCs or DCs. This may provide new insights into tumor metastasis and blood rheology. Significance: This in vivo imaging flow cytometry system holds great potential for assessing the efficiency of targeting CTCs with anticancer immune cells or drugs.
关键词： Cell Interaction,Circulating Tumor Cell,In Vivo Imaging Flow Cytometry,Artificial Neural Network,Dendritic Cell
更新于2025-09-23 15:22:29
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Raman spectroscopy and its use for live cell and tissue analysis
摘要： As research progresses in the field of life sciences, there is an increased demand for new technologies that can allow us to study intact cells and tissues. The quantitative analysis and mathematical modeling of living things based on empirical data is useful for connecting molecular biology to new areas, such as computational biology. Raman spectroscopy is regarded as one of the possible methods by which we can observe living organisms in a noninvasive manner. This could improve the quality of research in the field of medicine and health and will largely contribute to society in the future. The present review introduces some techniques based on Raman spectroscopy and evaluates their applications in intact live samples.
关键词： Raman probe,Raman spectroscopy,Biomedical,in vivo
更新于2025-09-23 15:22:29
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In Vivo Chemoselective Photoacoustic Imaging of Copper(II) in Plant and Animal Subjects
摘要： The detection of Cu2+ in living plants and animals is of great importance for environment monitoring and disease diagnosis. Here, a near-infrared (NIR) turn-on photoacoustic (PA) probe (denoted as LET-2) is developed for Cu2+ detection in living subjects, such as soybean sprouts and mice. The absorbance band of LET-2 shifts from 625 to 715 nm after the interaction with Cu2+, thus producing strong PA signal output at 715 nm (PA715) as an indicator. The PA715 value is increased as a function of the concentration of Cu2+ (0 × 10?6–20 × 10?6 m), with a calculated limit of detection of 10.8 × 10?9 m. More importantly, both in vitro and in vivo studies in soybean sprouts and mice indicate that the as-prepared LET-2 PA probe is highly sensitive and selective for Cu2+ detection. These findings provide a solution for in vivo detection of metal ions by using chemoselective PA probes.
关键词： animals,photoacoustic imaging,copper detection,in vivo,plants
更新于2025-09-23 15:22:29
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In vivo confocal microscopy morphometric analysis of corneal subbasal nerve plexus in dry eye disease using newly developed fully automated system
摘要： Purpose To evaluate in vivo confocal microscopy (IVCM) features of corneal subbasal nerve plexus (SNP) in the setting of dry eye disease (DED) using fully automated software BACCMetrics,^ and to further investigate its diagnostic performance in discriminating DED patients. Methods IVCM exams of SNP in DED patients and matched control subjects were performed using Heidelberg Retina Tomograph with the Rostock Cornea Module. The following parameters were obtained with ACCMetrics: corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrD). The Mann–Whitney U test was used to compare variables. Receiver operating characteristic curves with calculations of the area under the curve (AUC) were used to describe the accuracy of IVCM parameters for discriminating DED patients from controls. Results Thirty-nine DED patients and 30 control subjects were included. Significantly, lower values of CNFD, CNBD, and CNFL and higher value of CNFW were found in DED patients compared to controls (respectively, 20.5 ± 8.7 vs 25.4 ± 6.7 n/ mm2; 25.6 ± 20.1 vs 37.6 ± 21.5 n/mm2; 12.6 ± 4.4 vs 14.5 ± 2.9 mm/mm2; 0.021 ± 0.001 vs 0.019 ± 0.001 mm/mm2; always p < 0.024). CNFW value had the highest diagnostic power in discriminating DED patients (AUC = 0.828). When the diagnosis of DED was made based on either CNFW or CNBD, the sensitivity was 97.4% and the specificity 46.7%. Conclusions The software ACCMetrics was able to rapidly detect SNP alterations occurring in the setting of DED and showed good diagnostic performance in discriminating DED patients.
关键词： Dry eye,Sub-basal nerve plexus,Automated analysis,ACCMetrics,In vivo confocal microscopy
更新于2025-09-23 15:22:29
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Physiologically Stable Hydrophilic C60 Nanoparticles for Photodynamic Therapy
摘要： Hydrophilic C60 nanoparticles that are highly stable in living systems were prepared with sugammadex, an anionic γ-cyclodextrin derivative, via a simple procedure for use in biological applications. The prepared C60/sugammadex nanoparticles showed outstanding stability under physiological conditions and even in much harsher conditions. The sugammadex interacted with C60 nanoparticles through strong host-guest interactions on the particle surface, producing a negatively charged layer on the surface of nanoparticles, which contributed to the high stability of the nanoparticles. In addition, the nanoparticles were highly stable in the presence of singly charged cations which are present in abundance in living systems. The stable C60/sugammadex nanoparticles showed a significantly different biological behavior compared to less stable C60 nanoparticles after intravenous administration. Most of the C60 particles accumulated and remained in organs of the reticuloendothelial system (RES) after administration, which are susceptible to forming aggregates in physiological conditions. On the other hand, the C60/sugammadex nanoparticles showed a completely different biological behavior, i.e. longer blood circulation, low RES uptake and elimination with time from organs. The photodynamic activity of C60/sugammadex nanoparticles was evaluated both in vitro and in vivo, and an outstanding antitumor effect was achieved based on the generation of reactive oxygen species under light irradiation. We envision that such stable C60 nanoparticles would be a desirable approach for extending the biological applications of these materials and the precise evaluation of C60 activity in living systems.
关键词： nanoparticle,biodistribution,in vivo aggregation,photodynamic therapy,fullerene
更新于2025-09-23 15:22:29
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New Unsymmetrical Bisacridine Derivatives Noncovalently Attached to Quaternary Quantum Dots Improve Cancer Therapy by Enhancing Cytotoxicity toward Cancer Cells and Protecting Normal Cells
摘要： The use of nanoparticles for the controlled drug delivery to cells has emerged as a good alternative to traditional systemic delivery. Quantum dots (QDs) offer potentially invaluable societal benefits such as drug targeting and in vivo biomedical imaging. In contrast, QDs may also pose risks to human health and the environment under certain conditions. Here, we demonstrated that a unique combination of nanocrystals core components (Ag-In-Zn-S) would eliminate the toxicity problem and increase their biomedical applications. The alloyed quaternary nanocrystals Ag-In-Zn-S (QDgreen, Ag1.0In1.2Zn5.6S9.4; QDred, Ag1.0In1.0Zn1.0S3.5) were used to transport new unsymmetrical bisacridine derivatives (UAs, C-2028 and C-2045) into lung H460 and colon HCT116 cancer cells for improving the cytotoxic and antitumor action of these compounds. UAs were coupled with QD through physical adsorption. The obtained results clearly indicate that the synthesized nanoconjugates exhibited higher cytotoxic activity than unbound compounds, especially toward lung H460 cancer cells. Importantly, unsymmetrical bisacridines noncovalently attached to QD strongly protect normal cells from the drug action. It is worth pointing out that QDgreen or QDred without UAs did not influence the growth of cancer and normal cells, which is consistent with in vivo results. In noncellular systems, at pH 5.5 and 4.0, which relates to the conditions of endosomes and lysosomes, the UAs were released from QD-UAs nanoconjugates. An increase of total lysosomes content was observed in H460 cells treated with QDs-UAs which can affect the release of the UAs from the conjugates. Moreover, confocal laser scanning microscopy analyses revealed that QD-UAs nanoconjugates enter H460 cells more efficiently than to HCT116 and normal cells, which may be the reason for their higher cytotoxicity against lung cancer. Summarizing, the noncovalent attachment of UAs to QDs increases the therapeutic efficiency of UAs by improving cytotoxicity toward lung H460 cancer cells and having protecting effects on normal cells.
关键词： lung and colon cancer cells,unsymmetrical bisacridine derivatives,drug-carrier degradation pathway,pH-dependent release,cellular uptake,in vivo antitumor efficacy,Ag-In-Zn-S nanocrystals,cytotoxic activity
更新于2025-09-23 15:21:01