{"title":"TAggiXL: A Fluorescence-Traceable Cross-Linking Strategy for Unbiased Profiling of Protein Aggregation and Interactome Dynamics","authors":"Yuwen Chen, Yuxin An, Hui Pan, Zhou Gong, Zhiying Li, Jing Chen, Zhen Liang, Yukui Zhang, Yu Liu, Qun Zhao, Lihua Zhang","doi":"10.1021/acs.analchem.4c05071","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c05071","url":null,"abstract":"Protein aggregation is a hallmark of numerous degenerative diseases, yet its underlying mechanisms remain poorly understood due to the challenges in identifying the composition and interaction networks of these aggregates. To address this issue, we developed TAggiXL, a novel method that combines fluorescence-traceable aggregate isolation with cross-linking proteomics, significantly enhancing the efficiency and precision of isolating protein aggregates. This method facilitates unbiased profiling of aggregated proteomes and their interactomes in live cells. The TAggiXL approach leverages advanced cross-linking proteomics, density gradient centrifugation, and fluorescence tracking to provide detailed characterization of protein aggregation under various stress conditions including HSP90 and proteasome inhibition. Using TAggiXL, we identified key components and interactions within the aggregates, particularly highlighting E3 ubiquitin ligase TRIM26, which plays a crucial role in aggregate formation and autophagic clearance under stress and pathogenic conditions. Moreover, TAggiXL revealed that HSPA1B functions as a central interaction hub within the aggregated proteome. It preferentially interacts with intrinsically disordered regions (IDRs) of aggregate components and demonstrates dynamic behavior within the aggregate. In summary, TAggiXL offers a powerful tool for dissecting the complex composition and interaction networks of protein aggregates, with a significant potential to advance our understanding of protein aggregation in degenerative diseases. It also holds promise for the development of future therapeutic interventions.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"79 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuna Mi, Xinyuan Hu, Shaofeng Yuan, Hang Yu, Yahui Guo, Yuliang Cheng, Weirong Yao
{"title":"Unveiling the Correlation between Protein, Protein Corona, and Target Signal Loss in SERS Detection","authors":"Shuna Mi, Xinyuan Hu, Shaofeng Yuan, Hang Yu, Yahui Guo, Yuliang Cheng, Weirong Yao","doi":"10.1021/acs.analchem.4c05084","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c05084","url":null,"abstract":"The application of surface-enhanced Raman scattering (SERS) technology is hindered by the protein corona in a protein-rich complex matrix, which is a hot and important issue that needs consideration. However, the impact of the protein corona on SERS detection has not been fully studied. Herein, we selected three proteins, α-lactalbumin (α-La), β-lactoglobulin (β-Lg), and bovine serum albumin (BSA), as models for forming a protein corona, and melamine was employed as the target in SERS detection. The results indicate that three proteins form a protein corona on gold nanoparticles (AuNPs), leading to a significant loss of melamine signals. With increasing protein concentration, the degree of loss increases. The protein corona significantly inhibits target-induced nanoparticle aggregation, increases the distance between neighboring nanoparticles, and reduces the formation of “hot-spot” regions. Moreover, the adsorption capacity of AuNPs for melamine decreases, reducing the number of molecules that can achieve direct chemical enhancement. The Raman signal loss caused by different types of proteins, varies, even at the same molecule number, which is related to the deformability of proteins. This deformability determines the density of the protein corona formed on the surface of the AuNPs. Our results advance the fundamental understanding of the relationship between proteins, protein corona, and target signal loss in SERS detection, offering valuable insights for establishing models to predict Raman signal loss in protein-rich samples.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"79 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SERS-AI Based Detection and Bioanalysis of Malodorous Components in Kitchen Waste","authors":"Zhaoxian Chen, Kejin Chen, Wenrou Yu, Xiang Wang, Xi He, Qiang Zhang, Chunling Ge, Haiyang Shi, Yingzhou Huang","doi":"10.1021/acs.analchem.4c04699","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04699","url":null,"abstract":"The prevention and control of odor gas generated from kitchen waste are significant missions in research on environmental pollution. Because of the high complexity and variability of kitchen waste, the development of a suitable technique with high sensitivity for the accurate detection of odor gas is an urgent and core task in this frontier field. Here, a technique combining surface-enhanced Raman spectroscopy (SERS) and artificial intelligence (AI) is explored for detecting malodorous components in the leachate of kitchen waste. Initially, 1706 SERS spectra were collected from synthetic kitchen waste under various fermentation parameters. Several AI algorithms were used to classify three levels of odor intensity based on SERS spectra, among which the Random Forest Classifier algorithm model showed a high prediction accuracy of 86.5%. Then, by integrating Raman data, the AI algorithm model identified hydrogen sulfide (H<sub>2</sub>S) and ammonia (NH<sub>3</sub>) as the dominant malodorous components in the odor gas. Finally, the structural characteristics of the microbial communities are investigated. With the help of Raman’s intensities of malodorous components, many more insights into microorganisms in the fermentation process are revealed, which has important research value in the prevention and controlling of odor gas generated from kitchen waste. Furthermore, the microbial metabolic pathways of sulfur and nitrogen are discussed here. This SERS-AI-based novel technique not only has a broad potential for odor pollution but also could be applied to another complicated biochemical system with functional bacteria.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"64 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Analytical ChemistryPub Date : 2024-11-26Epub Date: 2024-11-14DOI: 10.1021/acs.analchem.4c02622
Luca Capelli, Federica Pedrini, Andrea C Di Pede, Alejandro Chamorro-Garcia, Neda Bagheri, Simone Fortunati, Marco Giannetto, Monica Mattarozzi, Roberto Corradini, Alessandro Porchetta, Alessandro Bertucci
{"title":"Synthetic Protein-to-DNA Input Exchange for Protease Activity Detection Using CRISPR-Cas12a.","authors":"Luca Capelli, Federica Pedrini, Andrea C Di Pede, Alejandro Chamorro-Garcia, Neda Bagheri, Simone Fortunati, Marco Giannetto, Monica Mattarozzi, Roberto Corradini, Alessandro Porchetta, Alessandro Bertucci","doi":"10.1021/acs.analchem.4c02622","DOIUrl":"10.1021/acs.analchem.4c02622","url":null,"abstract":"<p><p>We present a novel activity-based detection strategy for matrix metalloproteinase 2 (MMP2), a critical cancer protease biomarker, leveraging a mechanism responsive to the proteolytic activity of MMP2 and its integration with CRISPR-Cas12a-assisted signal amplification. We designed a chemical translator comprising two functional units─a peptide and a peptide nucleic acid (PNA), fused together. The peptide presents the substrate of MMP2, while the PNA serves as a nucleic acid output for subsequent processing. This chemical translator was immobilized on micrometer magnetic beads as a physical support for an activity-based assay. We incorporated into our design a single-stranded DNA partially hybridized with the PNA sequence and bearing a region complementary to the RNA guide of CRISPR-Cas12a. The target-induced nuclease activity of Cas12a results in the degradation of FRET-labeled DNA reporters and amplified fluorescence signal, enabling the detection of MMP2 in the low picomolar range, showing a limit of detection of 72 pg/mL. This study provides new design principles for a broader applicability of CRISPR-Cas-based biosensing.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":" ","pages":"18645-18654"},"PeriodicalIF":6.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shali Jiang, Can Xie, Ting Liu, Xiaomin Yuan, Jiaxin Zheng, Zimin Lian, Min Ouyang, Yongbo Peng, Liyi Zhou
{"title":"Robust Fluorescent Nanoprobe for Rapid Evaluation of the Selenium Supplementation Effect and Imaging","authors":"Shali Jiang, Can Xie, Ting Liu, Xiaomin Yuan, Jiaxin Zheng, Zimin Lian, Min Ouyang, Yongbo Peng, Liyi Zhou","doi":"10.1021/acs.analchem.4c04020","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04020","url":null,"abstract":"At present, an increasing number of people pay more attention to selenium-enriched food, but the quality of the selenium-enriched food varies. Therefore, there is an urgent need to develop a new tool to assess the effects of selenium supplementation in foods by rapidly detecting the levels of the metabolite selenium selenocysteine (Sec). In this work, a fluorescent nanoprobe <b>CS-Sec</b> was designed, synthesized, and characterized for Sec detection and imaging in living biosystems, which exhibited the advantages of good biocompatibility, excellent water solubility, high sensitivity, high selectivity, and rapid response (2.5 min) for Sec detection and imaging <i>in vitro</i> and <i>in vivo</i> and evaluation of selenium supplementation in selenium-rich foods. Specifically, <b>CS-Sec</b> was constructed by grafting alkyne groups on organic small-molecule fluorescent probes with azide groups on azido chitosan by click chemistry. A 2,4-dinitrophenyl ether (DNB) with a strong intramolecular charge transfer (ICT) effect was selected as a response group and fluorescence-quenching group, which had excellent chemical specificity toward Sec. In addition, <b>CS-Sec</b> has high selectivity and sensitivity toward Sec over other analytes, and an excellent limit of detection (LOD) is as low as 15 nM. Impressively, <b>CS-Sec</b> has been successfully used to detect and image the concentration of Sec in living HepG2 cells and mouse models with exciting results, indicating that the newly constructed <b>CS-Sec</b> can provide a robust molecule tool for the rapid evaluation of the selenium supplementation effect and imaging in the future.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"7 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ru Wu, Yue Cao, Yi Liu, Yang Zhou, Zixuan Chen, Jun-Jie Zhu
{"title":"Alkynyl Ligands Templated Assemblies of Silver Nanoclusters with Exceptional Electrochemiluminescence Activity for Pancreatic Cancer Specific tsRNAs Measurement","authors":"Ru Wu, Yue Cao, Yi Liu, Yang Zhou, Zixuan Chen, Jun-Jie Zhu","doi":"10.1021/acs.analchem.4c03758","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c03758","url":null,"abstract":"Proper manipulation of the ligand complex on the motifs of metal nanoclusters (MNCs) to form an ordered self-assembly is an effective approach to enhance the electrochemiluminescence (ECL) emission of MNCs. We report a facile approach for the preparation of self-assembled AgNCs (AgNCs<sub>Assy</sub>) induced by alkynyl ligands with enhanced ECL and stability. The formation of these AgNCs<sub>Assy</sub> was simultaneously driven by the diverse coordination modes of alkynyl ligands with Ag and intercluster interactions, for which it was found that the para-substituted alkynyl ligands exhibited apparently irregular nanoparticles, while the monosubstituted counterparts were present in the form of ribbons. The calculations revealed that the energy gap between the highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs) played a crucial role in their ECL emissions because of the substituent effects, especially, the low-lying LUMO levels could help to enhance the ECL emission. Moreover, mechanistic studies revealed that both the coreactant and alkynyl ligands made significant contributions to the ECL performance. Concurrently, the CRISPR-associated proteins (CRISPR-Cas) 12a system shows great potential in biosensing applications due to the advantages of easy design and precise targeting. As a proof of concept, we integrated the cascade amplification of catalytic hairpin assembly (CHA) circuit and the collateral cleavage activity of CRISPR-Cas12a to construct an ultrasensitive ECL biosensor for pancreatic cancer (PC)-specific tsRNAs, with a detection limit of 3.33 fM. This work is not only instructive for the synthesis of self-assembled MNCs with high ECL activities but also contributes to the understanding of the ECL mechanism of self-assembled MNCs.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"73 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Analytical ChemistryPub Date : 2024-11-26Epub Date: 2024-11-14DOI: 10.1021/acs.analchem.4c04386
Heyuhan Zhang, Ning Li, Fangying Shi, Feng Yuan, Shaoqiang Huang, Nianrong Sun, Chunhui Deng
{"title":"Plasma Metabolic Profiles via p-p Heterojunction-Assisted Laser Desorption/Ionization Mass Spectrometry for Advanced Warning and Diagnosis of Epidural-Related Maternal Fever.","authors":"Heyuhan Zhang, Ning Li, Fangying Shi, Feng Yuan, Shaoqiang Huang, Nianrong Sun, Chunhui Deng","doi":"10.1021/acs.analchem.4c04386","DOIUrl":"10.1021/acs.analchem.4c04386","url":null,"abstract":"<p><p>Epidural-related maternal fever (ERMF) heightens the risk of intrapartum fever, whereas effective prevention and treatment in clinical practice are currently lacking. Rapid and sensitive screening tools for ERMF are urgently needed to advance relevant research. In response to this challenge, we devise and craft porous Co<sub>3</sub>O<sub>4</sub>/CuO hollow polyhedral nanocages with p-p heterojunctions derived from metal-organic frameworks. We employ these p-p heterojunctions in conjunction with high-throughput mass spectrometry to conduct metabolic analysis of substantial plasma samples, with only about 0.03 μL per sample. Leveraging these p-p heterojunctions, metabolic signals from complex plasma can be amplified, with great reproducibility. By harnessing the power of machine learning on these metabolic signals, we are able to achieve advanced warning of ERMF with an area under the curve (AUC) of 0.887-0.975 by the differentially metabolic analysis of plasma samples collected upon admission. Furthermore, we can accurately diagnose ERMF with an AUC of 0.850-1.000 by analyzing plasma samples collected at the time of delivery from individuals who have received epidural analgesia. These breakthroughs offer invaluable insights for clinical decision making during labor and have the potential to significantly reduce the incidence of ERMF.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":" ","pages":"18824-18833"},"PeriodicalIF":6.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CRISPR/Cas13a Trans-Cleavage and Catalytic Hairpin Assembly Cascaded Signal Amplification Powered SERS Aptasensor for Ultrasensitive Detection of Gastric Cancer-Derived Exosomes.","authors":"Xinyue Gu, Jingjing Zhang, Jing Liang, Xinyu Liu, Xiyu He, Xiaoyuhao Jin, Chenlong Yan, Lianhui Wang, Chunyuan Song","doi":"10.1021/acs.analchem.4c03063","DOIUrl":"10.1021/acs.analchem.4c03063","url":null,"abstract":"<p><p>Cancer-derived exosomes carry a large number of specific molecular profiles from cancer cells and have emerged as ideal biomarkers for early cancer diagnosis. Accurate detection of ultralow-abundance exosomes in complex biological samples remains a great challenge. Herein, a novel SERS aptasensor powered by cascaded signal amplification of CRISPR/Cas13a <i>trans</i>-cleavage and catalytic hairpin assembly (CHA) was proposed for ultrasensitive detection of gastric cancer-derived exosomes, which included hairpin-structured recognition aptamers (MUC1-apt), cascaded signal amplification (i.e., CRISPR/Cas13a <i>trans</i>-cleavage and CHA), SERS tags, and silver nanorods (AgNRs) sensing chip. In the presence of SGC-7901 cell-derived exosomes, MUC1-apt specifically bound to MUC1 proteins highly expressed on exosomes <i>via</i> its contained MUC1 aptamer with its exposed RNA fragments activating the CRISPR/Cas13a <i>trans</i>-cleavage to cleave the uracil-modified hairpin reporter, and the cleavage products further triggered the downstream CHA reaction to form numerous duplexes, which can, in turn, capture a large number of SERS tags onto the AgNRs sensing chip to generate a significantly enhanced Raman signal. The proposed SERS aptasensor exhibits good performance on analysis of exosomes, i.e., rapid response within 60 min, single-particle sensitive detection from a 2 μL biological sample, good specificity in distinguishing SGC-7901 cell-derived exosomes against other exosomes, good uniformity, excellent repeatability, and satisfactory recoveries in human serum, and good universality to expand the detection of multiplex exosomes, which indicates that the SERS aptasensor provides a valuable reference for clinical diagnosis of early cancer.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":" ","pages":"18681-18689"},"PeriodicalIF":6.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter K. Weber, Marc Debliqui, Céline Defouilloy, Xavier Mayali, Ming-Chang Liu, Rachel Hestrin, Jennifer Pett-Ridge, Rhona Stuart, Megan Morris, Christina Ramon, Danielle M. Jorgens, Reena Zalpuri, Laurent Arnoldi, Jérôme Farcy, Nicolas Saquet, Sarah Vitcher Fichou, Ludovic Renaud, Aurélien Thomen
{"title":"The NanoSIMS-HR: The Next Generation of High Spatial Resolution Dynamic SIMS","authors":"Peter K. Weber, Marc Debliqui, Céline Defouilloy, Xavier Mayali, Ming-Chang Liu, Rachel Hestrin, Jennifer Pett-Ridge, Rhona Stuart, Megan Morris, Christina Ramon, Danielle M. Jorgens, Reena Zalpuri, Laurent Arnoldi, Jérôme Farcy, Nicolas Saquet, Sarah Vitcher Fichou, Ludovic Renaud, Aurélien Thomen","doi":"10.1021/acs.analchem.4c03091","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c03091","url":null,"abstract":"The high lateral resolution and sensitivity of the NanoSIMS 50 and 50L series of dynamic SIMS instruments have enabled numerous scientific advances over the past 25 years. Here, we report on the NanoSIMS-HR, the first major upgrade to the series, and analytical tests in a suite of sample types, including an aluminum sample containing silicon crystals, microalgae, and plant roots colonized with a symbiotic fungus. Significant improvements have been made in the Cs<sup>+</sup> ion source, high voltage (HV) control, stage reproducibility, and other aspects of the instrument that affect performance. The modified design of the NanoSIMS-HR thermal-ionization Cs<sup>+</sup> source enables a 5 pA primary ion beam to be focused into a 100 nm spot, a ∼2.5-fold increase compared to Cs<sup>+</sup> sources on previous instruments (∼2 pA at 100 nm). The brightness of the new Cs<sup>+</sup> source enables an ultimate lateral resolution as high as 30 nm and improved detection limits for a given analysis area. Sample stage movement accuracy is higher than 500 nm, enabling many-fold higher throughput automated analyses. With the new HV control, the primary ion beam impact energy can be reduced from 16 to 2 keV, which enables higher depth resolution during depth profiling (a 2-fold improvement), albeit with a 5-fold decrease in lateral resolution. In the NanoSIMS-HR, the secondary ion column and detection system are identical to those used in the previous series, and the isotopic analysis performance is as precise as in previous NanoSIMS instruments.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"27 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Analytical ChemistryPub Date : 2024-11-26Epub Date: 2024-11-14DOI: 10.1021/acs.analchem.4c05202
Xiaofeng Xia, Minrong Huang, Yazhou Hu, Zhe Zhou, Yiyu Chen, Juan Wang, Jun Ren, Erfei Wang, Feiyi Wang
{"title":"Rational Design of a Tandem Activatable Fluorescent Probe for Differential Diagnosis and Therapeutic Assessment of Hepatocellular Carcinoma.","authors":"Xiaofeng Xia, Minrong Huang, Yazhou Hu, Zhe Zhou, Yiyu Chen, Juan Wang, Jun Ren, Erfei Wang, Feiyi Wang","doi":"10.1021/acs.analchem.4c05202","DOIUrl":"10.1021/acs.analchem.4c05202","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a formidable disease, distinguished by its high aggressiveness and dismal outcomes. Although leucine aminopeptidase (LAP) has been widely employed as a biomarker in biological imaging of HCC, it is still susceptible to interference from false-positive signals activated in injured liver tissues. In this study, based on the significant difference of GSH levels in alcohol-damaged liver tissues and tumor tissues, a dual-tandem activatable probe (PCLT) was designed for differential diagnosis and treatment guidance of HCC by near-infrared fluorescence (NIRF) imaging. This probe comprised a dual-locked hemicyanine dye decorated with a tetraethylene glycol chain and dual-recognition unit of glutathione (GSH) and LAP, which could be sequentially cleaved by GSH and LAP to restore its NIRF signal. PCLT excellently discriminated orthotopic HCC from ALI far earlier (7 days) than histological analysis (28 days) and exhibited higher specificity toward early orthotopic HCC than the single-locked probe (PCL). In addition, PCLT is capable of accurately delineating the tumor contour, assisting in surgical resection of HCC tumors under fluorescence visualization, and noninvasively assessing the antitumor effect of HCC chemotherapy during ferroptosis, thereby presenting promising clinical implications for clinical diagnosis and therapy of HCC.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":" ","pages":"18898-18906"},"PeriodicalIF":6.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}