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BODIPY analogs are promising photosensitizers for molecular phototherapy; however, they exhibit high dark cytotoxicity and limited singlet oxygen generation capacity. In this study, we developed self-assembled core-shell nanophotosensitizers by linking a bipyridine group to BODIPY (Bpy-BODIPY) and promoting J-aggregation on gold nanourchins. This design enhances photostability and reduces the energy gap between the lowest singlet excited state and the lower triplet state, facilitating efficient singlet oxygen production. Notably, Bpy-BODIPY@Au significantly suppresses tau protein aggregation and enhances neuroprotective action, even in the presence of a phosphatase inhibitor. This work broadens the application of BODIPY chemistry to nanoagents for neuroprotective therapy.
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The development of durable photosensitizers is pivotal for advancing phototherapeutic applications in biomedicine. Here, we introduce a core-shell azobenzene-spiropyran structure on gold nanoparticles, engineered to enhance singlet oxygen generation. These nano-photosensitizers exhibit increased structural stability and thermal resistance, as demonstrated by slowed O-N-C bond recombination dynamics via in-situ Raman spectroscopy. Notably, the in-situ formation of merocyanine and a light-induced compact shell arrangement extend its half-life from 47 minutes to over 154 hours, significantly boosting singlet oxygen output. The nano-photosensitizer also shows high biocompatibility and notably inhibits tau protein aggregation in neural cells, even with phosphatase inhibitors. Further, it promotes dendritic growth in neuro cells, doubling typical lengths. This work not only advances chemical nanotechnology but also sets a foundation for developing long-lasting phototherapy agents for treating neurodegenerative diseases.
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Rapid identification of cancer cells is crucial for clinical treatment guidance. Laser tweezer Raman spectroscopy (LTRS) that provides biochemical characteristics of cells can be used to identify cell phenotypes through classification models in a non-invasive and label-free manner. However, traditional classification methods require extensive reference databases and clinical experience, which is challenging when sampling at inaccessible locations. Here, we describe a classification method combing LTRS with deep neural network (DNN) for differential and discriminative analysis of multiple liver cancer (LC) cells. By using LTRS, we obtained high-quality single-cell Raman spectra of normal hepatocytes (HL-7702) and liver cancer cell lines (SMMC-7721, Hep3B, HepG2, SK-Hep1 and Huh7). The tentative assignment of Raman peaks indicated that arginine content was elevated and phenylalanine, glutathione and glutamate content was decreased in liver cancer cells. Subsequently, we randomly selected 300 spectra from each cell line for DNN model analysis, achieving a mean accuracy of 99.2%, a mean sensitivity of 99.2% and a mean specificity of 99.8% for the identification and classification of multiple LC cells and hepatocyte cells. These results demonstrate the combination of LTRS and DNN is a promising method for rapid and accurate cancer cell identification at single cell level.
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Neoplasias Hepáticas , Pinzas Ópticas , Humanos , Espectrometría Raman/métodos , Redes Neurales de la Computación , Línea CelularRESUMEN
Singlet oxygen (1O2) has been recently identified as a key molecule against toxic Aß aggregation, which is associated with the currently incurable Alzheimer's disease (AD). However, limited research has studied its efficiency against tau protein aggregation, the other major hallmark of AD. Herein, we designed and synthesized boron-dipyrromethene (BODIPY)-ruthenium conjugates and isolated three isomers. Under visible-light irradiation, the ε isomer can be photoactivated and efficiently generate singlet oxygen. Particularly, the complex demonstrated successful results in attenuating tauopathyâan appreciable decrease to 43 ± 2% at 100 nM. The photosensitizer was further found to remarkably promote neurite outgrowth and significantly increased the length and number of neurites in nerve cells. As a result of effective photoinduced singlet oxygen generation and proactive neurite outgrowth, the hybrid design has great potential for therapeutics for Alzheimer's disease.
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Enfermedad de Alzheimer , Rutenio , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Boro/farmacología , Proyección Neuronal , Fármacos Fotosensibilizantes/farmacología , Agregado de Proteínas , Rutenio/farmacología , Oxígeno Singlete/metabolismo , Proteínas tau/metabolismoRESUMEN
Observing a Goos-Hänchen (GH) shift of the incident light beam provides a simple and convenient method of detecting fast phase variations without the need for cumbersome direct phase measurements. Here, we show that few-monolayers-thick van der Waals structures (WS2 , MoSe2 and graphene) nano-engineered onto a plasmonic surface can enhance the phase variation sensitivity to analyte presence, leading to more than 3 orders of magnitude increase in the Goos-Hänchen shift (ca. 886â mm/RIU for a WS2 /graphene/Au multilayer). The detection limit is evaluated to be as low as 0.1â aM (6.7â pg/mL) for bovine serum albumin protein with molecular weight of 67â kDa and 1â fM (24.4â ng/mL) for biotin (244â Da) molecules.
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GrafitoRESUMEN
Early screening and precise staging are crucial for reducing mortality in patients with nasopharyngeal carcinoma (NPC). This study aimed to assess the performance of blood protein surface-enhanced Raman scattering (SERS) spectroscopy, combined with deep learning, for the precise detection of NPC. A highly efficient protein SERS analysis, based on a membrane purification technique and super-hydrophobic platform, was developed and applied to blood samples from 1164 subjects, including 225 healthy volunteers, 120 stage I, 249 stage II, 291 stage III, and 279 stage IV NPC patients. The proteins were rapidly purified from only 10 µL of blood plasma using the membrane purification technique. Then, the super-hydrophobic platform was prepared to pre-concentrate tiny amounts of proteins by forming a uniform deposition to provide repeatable SERS spectra. A total of 1164 high-quality protein SERS spectra were rapidly collected using a self-developed macro-Raman system. A convolutional neural network-based deep-learning algorithm was used to classify the spectra. An accuracy of 100% was achieved for distinguishing between the healthy and NPC groups, and accuracies of 96%, 96%, 100%, and 100% were found for the differential classification among the four NPC stages. This study demonstrated the great promise of SERS- and deep-learning-based blood protein testing for rapid, non-invasive, and precise screening and staging of NPC.
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The medical fraternity is currently burgeoned and stressed with a huge rush of patients who have inflammatory conditions, metabolite diseases, and cardiovascular diseases. In these circumstances, advanced sensing technologies could have a huge impact on the quality of life of patients. Given plasmonic resonance effects significantly improve the ability to rapidly and accurately detect biological markers, plasmonic technology is harnessed to develop a fast and accurate diagnosis that can provide timely intervention with the diseases and can also aid the recovery process by complementing the therapy stage. In this short review, we provide an overlook of how the field of plasmonic sensing has revolutionized the field of medical diagnostics. This article reviews the fundamentals and development of plasmonics. In addition, we highlight the sensitivity of various SPR and LSPR sensors. The chemistry for functionalizing plasmonic sensors is also discussed. This review also outlines some general suggestions for future directions that we feel might be useful to advance our understanding of the universe or speed up the development of plasmonic sensors in the future.
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Técnicas Biosensibles , Resonancia por Plasmón de Superficie , Humanos , Calidad de VidaRESUMEN
We report herein a porous supramolecular framework formed by a linear mononuclear Au(I) complex (1) via the tongue-and-groove-like joinery between the pentiptycene U-cavities (grooves) and the rod-shaped π-conjugated backbone and alkyl chains (tongues) with the assistance of C-H···π and aurophilic interactions. The framework contains distorted tetrahedral Au4 units, which undergo stepwise and persistent photoinduced Au(I)-Au(I) bond shortening (excited-state aurophilicity), leading to multicolored luminescence photochromism. The one-dimensional pore channels could accommodate different solvates and guests, and the guest inclusion-induced luminescence enhancement (up to 300%) and/or vapochromism are characterized. A correlation between the aurophilic bonding and the luminescence activity is uncovered by TDDFT calculations. Isostructural derivatives 2 and 3 corroborate both the robustness of the porous supramolecular assembly and the mechanisms of the stimulation-induced luminescence properties of 1. This work demonstrates the cooperation of aurophilicity and structural porosity and adaptability in achieving novel supramolecular photochemical properties.
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Carbon monoxide (CO) plays an important role in signaling in cells, making its use as a therapeutic tool highly intriguing. Reduced burst emissions are important to avoid the cytotoxicity and tissue damage caused by CO. Here, we developed a stable diiron carbonyl [FeFe] hydrogenase agent that enables prolonged CO release activity (half-life of over 9 h) in cells. The integrated analysis allowed the identification of the key intermediate sites and CO accumulations with subcellular resolution. We observed that the [FeFe]A complex was enriched in neurons with S-methyl bond rupture. Furthermore, the [FeFe]A complex efficiently reduced the aggregation of tau proteins (49.3% reduction) and showed superior biocompatibility in nerve cells (â¼ 95% survival).
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Hidrogenasas , Proteínas Hierro-Azufre , Monóxido de Carbono/química , Dominio Catalítico , Desmetilación , Hidrogenasas/química , Proteínas Hierro-Azufre/químicaRESUMEN
Monitoring the levels of cancer biomarkers is essential for cancer diagnosis and evaluation. In this study, a novel sandwich type sensing platform based on surface-enhanced Raman scattering (SERS) technology was developed for the detection of carcinoembryonic antigen (CEA), with a limit of detection (LOD) of 0.258â ng/mL. In order to achieve sensitive detection of CEA in complex samples, gold nanoparticle monolayer modified with CEA antibodies and with aptamer-functionalized probes was fabricated to target CEA. Two gold layers were integrated into the SERS platform, which greatly enhanced the signal of the probe by generating tremendous "hot spots". Meanwhile, the intensity ratio of Raman probes and the second-order peak of the silicon wafer was used to achieve dynamic calibration of the Raman probe signal. Excitingly, this sensing platform was capable of distinguishing cancer patients from healthy individuals via CEA concentrations in blood samples with the accuracy of 100%. This sandwich structure SERS sensing platform presented promising potential to be an alternative tool for clinical biomarker detection in the field of cancer diagnosis.
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The limited availability of nasopharyngeal carcinoma-related progression biomarker array kits that offer physicians comprehensive information is disadvantageous for monitoring cancer progression. To develop a biomarker array kit, systematic identification and differentiation of a large number of distinct molecular surface-enhanced Raman scattering (SERS) reporters with high spectral temporal resolution is a major challenge. To address this unmet need, we use the chemistry of metal carbonyls to construct a series of unique SERS reporters with the potential to provide logical and highly multiplex information during testing. In this study, we report that geometric control over metal carbonyls on nanotags can produce 14 distinct barcodes that can be decoded unambiguously using commercial Raman spectroscopy. These metal carbonyl nanobarcodes are tested on human blood samples and show strong sensitivity (0.07 ng/mL limit of detection, average CV of 6.1% and >92% degree of recovery) and multiplexing capabilities for MMPs.
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Técnicas Biosensibles/métodos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Espectrometría Raman , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/química , Progresión de la Enfermedad , Metaloproteinasas de la Matriz/sangre , Metaloproteinasas de la Matriz/química , Nanopartículas del Metal/química , Nanogeles/química , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Compuestos Organometálicos/química , Sensibilidad y Especificidad , Propiedades de SuperficieRESUMEN
The detection of carbohydrates in human body fluids is critical for disease diagnosis and healthy monitoring. Despite recent advances in glucose sensing, multiplex detection of different carbohydrates within a single assay that is capable of efficiently providing richer health information remains challenging. Herein, we report a versatile surface-enhanced Raman spectroscopy-based platform for the quantitative detection of monosaccharides (glucose, fructose, and galactose) in one test using a displace-and-trap mechanism. Moreover, due to the use of multiple optical interference-free (1800-2200 cm-1) signal-independent Raman probes, the detection range of this platform (0.125-7 mg/dL) perfectly covers physiological concentrations, enabling the quantitative detection of glucose and galactose in clinical human saliva samples. This work provides a noninvasive and high-efficiency potential tool for the screening of clinical diabetes and other carbohydrate-related diseases.
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Saliva , Espectrometría Raman , Carbohidratos , Fructosa , Glucosa , HumanosRESUMEN
Quinone methides (QMs) are very important intermediates in chemistry. These species are most often generated in situ with metal oxidants and transition metal complexes. Here, tip-enhanced Raman spectroscopy (TERS) has been implemented to investigate the in situ oxidative generation of a QM species from alkylphenols facilitated by a transition metal complex. Using TERS, the metal oxidant-mediated transformation of a phenol species has been observed. The subsequent oxidative addition reaction of QM has also been identified based on distinct vibrational features, which have been assigned based on density functional theory (DFT). This study may establish TERS as a chemical detection tool for various QM-mediated reactions.
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Indolquinonas/química , Espectrometría Raman/métodos , Línea Celular Tumoral , Teoría Funcional de la Densidad , Humanos , Oxidación-ReducciónRESUMEN
A background-free photoinduced enhanced Raman (PIER) probe for highly sensitive detection of tyrosine dimerization process due to oxidative reaction in inflammatory cells is presented. The PIER probe could monitor oxidative reaction in real time by producing time-resolved spectral with discrete changes in Raman intensity. To the best of our knowledge, this is the first report on C≡C probes with PIER and vastly improved Raman activity. These results will contribute to the cutting edge of development of stable and highly sensitive chemical imaging technology.
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Dimerización , Imagen Molecular , Procesos Fotoquímicos , Espectrometría Raman , Tirosina/química , Carbono/química , Línea Celular , Inflamación/patología , Oxidación-Reducción , Tirosina/metabolismoRESUMEN
Anthracene-pentiptycene hybrid systems 1-Cn, where n refers to the number of carbon atoms in the linear alkyl chain, crystallize in three different polymorphs, denoted Y (yellow), G (green), and B (blue) forms in terms of the fluorescence color. While all Y-form crystals show the same yellow-to-blue fluorescence color response to the photomechanical stress generated by the anthracene [4+4] photodimerization reaction, the four G forms exhibit distinct photomechanofluorochromism (PMFC): from green to blue for G-1-C4, to orange for G-1-C7, to red for G-1-C8, and to red then blue for G-1-C9, and the B forms show no photochromic activity. The intriguing RGB three-color PMFC and abnormal topochemical reactivity of G-1-C9 are attributed to inherent softness of the crystal lattice.
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Detection of chemical reactions in living cells is critical in understanding physiological metabolic processes in the context of nanomedicine. Carbon monoxide (CO) is one of the important gaseous signaling molecules. Surface-enhanced Raman spectroscopy (SERS)-based CO-releasing nanoparticles (CORN) is utilized to investigate the chemical reaction of CO delivery in live cells. Using SERS CORN, carbonyl dissociation from CORN-Ag-CpW(CO)3 to CORN-Ag-CpW(CO)2 in live cells is observed. The subsequent irreversible degradation to CO-free CORN is a consequence of oxidative stress in cells. This observation affirms the step transition of CORN-Ag-CpW(CO)3 in cellular: CORN-Ag-CpW(CO)3 first proceeds via a direct loss of one CO followed by a oxidative decomposition giving rise to CORN-Ag-WO3 and as well as the release of one equivalents of CO. Importantly, the decarbonylation process can be correlated with the level of inflammatory biomarkers. For the first time, we provide unambiguous evidence for the steps transition of CO-release mechanism in cellular.
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Monóxido de Carbono/metabolismo , Nanopartículas del Metal/administración & dosificación , Plata/administración & dosificación , Tungsteno/administración & dosificación , Animales , Línea Celular , Citocinas/metabolismo , Humanos , Ratones , Espectrometría RamanRESUMEN
The detection of cancer invasion is crucial for diagnosis. In this report, we employed a TERS tip and SERS nanotags to create a cell signaling based nano-sensing system. This system is capable of creating a reversible phosphorylation/de-phosphorylation cycle for TERS measurement. The reversible TERS sensing is then paired with a downstream binding domain, Src homology region 2 (SH2), which is associated with the cell signaling for cancer cell invasion. Such a system offers the advantages of convenient detection of nanotags and high sensitivity as validated in a cell model.
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A dual signal amplification method based on surface-enhanced Raman scattering (SERS) is developed by photo-triggered release of SERS probes from mesoporous silica-coated Au nanorods (SiO2@Au) and the use of a specially-designed SERS substrate with an internal reference. Two metal carbonyl (metal-CO) labels (Os-SCO and Re-SCO) are proposed here as novel interference-free labels. Results demonstrate that tumor-related DNA can be quantitatively detected by this reliable and ultra-sensitive SERS platform.
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Complejos de Coordinación/química , ADN de Neoplasias/análisis , Nanotubos/química , Espectrometría Raman , ADN de Neoplasias/metabolismo , Oro/química , Humanos , Rayos Láser , Neoplasias/genética , Neoplasias/patología , Osmio/química , Renio/química , Dióxido de Silicio/químicaRESUMEN
Tip-enhanced Raman spectroscopy (TERS) is capable of probing specific molecular information with high sensitivity, but dual chemical sensing remains a challenge. Another major hindrance to TERS chemical detection in biosamples such as blood is the interference from the strong absorptions of biomolecules. Herein, we report the preparation of an organometallic-conjugated TERS tip. We demonstrate that organometallic chemistry can be perfectly coupled with TERS for dual-molecule sensing. The unique Raman signals generated by the organometallic compound circumvent signal interference from the biomolecules in blood, allowing the rapid analysis of two important molecules (glucose and thiol) in ultralow volume (50 nL) samples. This enabled a correlation between the thiol and glucose levels in the blood of nondiabetic and diabetic patients to be drawn.
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Glucemia/metabolismo , Diabetes Mellitus/sangre , Compuestos Organometálicos , Espectrometría Raman , Compuestos de Sulfhidrilo/sangre , Humanos , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacologíaRESUMEN
By taking advantage of the spectral properties of metal carbonyls, we have designed a surface-enhanced Raman spectroscopy (SERS) ratiometric assay for measuring cell-free circulating DNA (cfDNA) from Epstein-Barr virus in blood for nasopharyngeal carcinoma (NPC). This assay consists of a rhenium carbonyl (Re-CO) to serve as a DNA probe, an osmium carbonyl (Os-CO) embedded within the SERS-active substrate as an internal reference, and a streptavidin layer on the surface of the substrate. Hybridization of cfDNA with biotinylated-capture sequence leads to immobilization of cfDNA on the substrate. The binding of Re-CO via daunorubicin (DNR) to cfDNA is accompanied by an appearance of a strong symmetry stretching vibrations peak at 2113 cm-1, which has spectral overlap with Os-CO (2025 cm-1). This results in an increase in the I2113/ I2025 ratio and quantitatively correlates with cfDNA. This SERS assay can be readily used to detect cfDNA in blood samples from patients due to the intensity ratio of I2113/ I2025 lying in a silent region (1780-2200 cm-1) in the SERS spectrum of the biomolecules.