{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:17:17Z","timestamp":1790000237242,"version":"4.0.1"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"15","license":[{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/na","name":"the Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["FRF-TP-19-010A3, FRF-BD-18-001B and FRF-BR-18-009B"],"award-info":[{"award-number":["FRF-TP-19-010A3, FRF-BD-18-001B and FRF-BR-18-009B"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recently, multiplexed ratiometric fluorescence sensors for detecting several analytes have received much interest because of their multifunctionality. Here, we fabricate a novel trinity fluorescent nanoprobe in which one small-molecule fluorophore, blue-emissive dityrosine (diTyr) residues, and two nanomaterial fluorophores, green-emissive CdS quantum dots (CdSQDs) and red-emissive gold nanoclusters (AuNCs), are cocaged in a bovine serum albumin (BSA) molecule. The large differences of Stokes shifts among diTyr residues, CdSQDs, and AuNCs ensure their emission at a single excitation wavelength. The nanoprobes can be facilely integrated using two-step synthetic reactions. DiTyr residues and AuNCs are formed and bound to the protein cage through the redox reaction between Au3+ and tyrosine residues of BSA, and the CdSQDs are followed to be conjugated to the modified BSA cage-templated CdS combination reaction. With established benign biocompatibility, the nanoprobes can ratiometrically detect intracellular glutathione by significantly enhancing the green emission of the conjugated CdSQDs. Likewise, the ratiometric sensing of solution alkalinity and tris(2-carboxyethyl)phosphine can be achieved using blue-emitted diTyr residues and red-emitted AuNCs as the responsive units, respectively, and the corresponding other two fluorophores as the reference signals. This study addresses a concept of trinity fluorescence ratiometric sensing system with multiple targets and optional references, which should be a promising pathway to meet the challenges from complexing biochemical environments and multivariate analysis.<\/jats:p>","DOI":"10.1021\/acsomega.0c00711","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T14:21:20Z","timestamp":1586442080000},"page":"8943-8951","source":"Crossref","is-referenced-by-count":10,"title":["Rational Design of \u201cThree-in-One\u201d Ratiometric\nNanoprobes: Protein-Caged Dityrosine, CdS Quantum Dots, and Gold Nanoclusters"],"prefix":"10.1021","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1438-8600","authenticated-orcid":true,"given":"Tong","family":"Shu","sequence":"first","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Sun","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Bai","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangfang","family":"Lin","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziping","family":"Zhou","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5342-1552","authenticated-orcid":true,"given":"Lei","family":"Su","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0035-3821","authenticated-orcid":true,"given":"Xueji","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]},{"name":"Shenzhen University Health Science Center , , , ,","place":["Shenzhen, Guangdong, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"key":"2026092109071396800_cit1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3389\/fchem.2014.00063","article-title":"Nanomaterials\nfor biosensing applications:\na review","volume":"2","author":"Holzinger","year":"2014","journal-title":"Front. Chem."},{"key":"2026092109071396800_cit2","doi-asserted-by":"publisher","first-page":"10869","DOI":"10.1021\/cr400532z","article-title":"Functional\nnanomaterials for phototherapies of cancer","volume":"114","author":"Cheng","year":"2014","journal-title":"Chem. Rev."},{"key":"2026092109071396800_cit3","doi-asserted-by":"publisher","first-page":"18977","DOI":"10.1021\/jacs.9b05776","article-title":"Real Time\nMonitoring of the Dynamic Intracluster Diffusion of Single Gold Atoms\ninto Silver Nanoclusters","volume":"141","author":"Zheng","year":"2019","journal-title":"J. Am. Chem. Soc."},{"key":"2026092109071396800_cit4","doi-asserted-by":"publisher","first-page":"8139","DOI":"10.1002\/anie.201903584","article-title":"Aurophilic Interactions in the Self-Assembly\nof Gold Nanoclusters into Nanoribbons with Enhanced Luminescence","volume":"58","author":"Wu","year":"2019","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026092109071396800_cit5","doi-asserted-by":"publisher","first-page":"1802751","DOI":"10.1002\/adma.201870358","article-title":"Engineering\nFunctional Metal Materials at the Atomic Level","volume":"30","author":"Yao","year":"2018","journal-title":"Adv. Mater."},{"key":"2026092109071396800_cit6","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.nantod.2017.12.009","article-title":"Heterogeneous catalysis by gold and\ngold-based bimetal nanoclusters","volume":"18","author":"Zhao","year":"2018","journal-title":"Nano Today"},{"key":"2026092109071396800_cit7","doi-asserted-by":"publisher","first-page":"9318","DOI":"10.1021\/acsnano.8b04233","article-title":"Large-Scale\nSynthesis, Crystal Structure, and Optical Properties of the Ag146Br2(SR)80\nNanocluster","volume":"12","author":"Song","year":"2018","journal-title":"ACS Nano"},{"key":"2026092109071396800_cit8","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1021\/acs.accounts.8b00383","article-title":"Toward the Tailoring Chemistry of Metal Nanoclusters for Enhancing\nFunctionalities","volume":"51","author":"Higaki","year":"2018","journal-title":"Acc. Chem. Res."},{"key":"2026092109071396800_cit9","doi-asserted-by":"publisher","first-page":"8479","DOI":"10.1002\/anie.201903256","article-title":"Tuning the\nIn Vivo Transport of Anticancer Drugs Using Renal-Clearable Gold Nanoparticles","volume":"58","author":"Peng","year":"2019","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026092109071396800_cit10","doi-asserted-by":"publisher","first-page":"12076","DOI":"10.1002\/anie.201905738","article-title":"Correlating Anticancer\nDrug Delivery Efficiency with Vascular Permeability of Renal Clearable\nVersus Non-renal Clearable Nanocarriers","volume":"58","author":"Peng","year":"2019","journal-title":"Angew.\nChem., Int. Ed."},{"key":"2026092109071396800_cit11","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/s41565-019-0496-9","article-title":"On the issue of transparency\nand reproducibility in nanomedicine","volume":"14","author":"Leong","year":"2019","journal-title":"Nat. Nanotechnol."},{"key":"2026092109071396800_cit12","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1021\/acsnano.8b08103","article-title":"Surface Coverage-Regulated\nCellular Interaction of Ultrasmall Luminescent Gold Nanoparticles","volume":"13","author":"Gong","year":"2019","journal-title":"ACS Nano."},{"key":"2026092109071396800_cit13","doi-asserted-by":"publisher","first-page":"100767","DOI":"10.1016\/j.nantod.2019.100767","article-title":"Recent\nadvances in synthesizing metal nanocluster-based\nnanocomposites for application in sensing, imaging and catalysis","volume":"28","author":"Shang","year":"2019","journal-title":"Nano Today"},{"key":"2026092109071396800_cit14","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1039\/c9qm00165d","article-title":"Biomolecule-assisted\nsynthesis and functionality of\nmetal nanoclusters for biological sensing: a review","volume":"3","author":"Wang","year":"2019","journal-title":"Mater. Chem. Front."},{"key":"2026092109071396800_cit15","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.talanta.2019.03.068","article-title":"Ultrasmall Au nanoclusters\nfor biomedical and biosensing applications: A mini-review","volume":"200","author":"Zhang","year":"2019","journal-title":"Talanta"},{"key":"2026092109071396800_cit16","doi-asserted-by":"publisher","first-page":"12065","DOI":"10.1021\/acs.jpcc.5b03224","article-title":"Hidden Dityrosine Residues\nin Protein-Protected Gold Nanoclusters","volume":"119","author":"Su","year":"2015","journal-title":"J. Phys.\nChem. C"},{"key":"2026092109071396800_cit17","doi-asserted-by":"publisher","first-page":"11193","DOI":"10.1021\/acs.analchem.6b03418","article-title":"Chemical Etching of\nBovine Serum Albumin-Protected Au25 Nanoclusters for Label-Free and\nSeparation-Free Ratiometric Fluorescent Detection of Tris(2-carboxyethyl)phosphine","volume":"88","author":"Shu","year":"2016","journal-title":"Anal. Chem."},{"key":"2026092109071396800_cit18","doi-asserted-by":"publisher","first-page":"5033","DOI":"10.1039\/c8tc00448j","article-title":"Dual-emissive\ngold nanoclusters for label-free and\nseparation-free ratiometric fluorescence sensing of 4-nitrophenol\nbased on the inner filter effect","volume":"6","author":"Shu","year":"2018","journal-title":"J. Mater.\nChem. C"},{"key":"2026092109071396800_cit19","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1021\/jacs.7b11712","article-title":"Conformational Change-Induced\nFluorescence of Bovine Serum Albumin-Gold\nComplexes","volume":"140","author":"Dixon","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"2026092109071396800_cit20","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.molimm.2012.05.011","article-title":"Structural\nand immunologic characterization of bovine, horse, and rabbit serum\nalbumins","volume":"52","author":"Majorek","year":"2012","journal-title":"Mol. Immunol."},{"key":"2026092109071396800_cit21","doi-asserted-by":"publisher","first-page":"1970031","DOI":"10.1002\/ppsc.201970031","article-title":"Metal Nanoclusters\u2013Based\nRatiometric Fluorescent Probes from Design to Sensing Applications","volume":"36","author":"Zhao","year":"2019","journal-title":"Part. Part. Syst. Char."},{"key":"2026092109071396800_cit22","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1039\/c7cs00612h","article-title":"Ratiometric optical\nnanoprobes enable accurate molecular detection\nand imaging","volume":"47","author":"Huang","year":"2018","journal-title":"Chem. Soc. Rev."},{"key":"2026092109071396800_cit23","doi-asserted-by":"publisher","first-page":"4185","DOI":"10.1039\/c4cs00280f","article-title":"Small molecule-based ratiometric\nfluorescence probes for cations, anions, and biomolecules","volume":"44","author":"Lee","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"2026092109071396800_cit24","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.1039\/c9cc10028h","article-title":"A dual-ratiometric\nfluorescent probe for individual and continuous detection of H2S and\nHClO in living cells","volume":"56","author":"Yue","year":"2020","journal-title":"Chem. Commun."},{"key":"2026092109071396800_cit25","doi-asserted-by":"publisher","first-page":"3876","DOI":"10.1039\/c9tb00640k","article-title":"Synthesis of gold\nnanocluster-loaded lysozyme nanoparticles for label-free ratiometric\nfluorescent pH sensing: applications to enzyme\u2013substrate systems\nand cellular imaging","volume":"7","author":"Chandirasekar","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"2026092109071396800_cit26","doi-asserted-by":"publisher","first-page":"11210","DOI":"10.1039\/c6nr02341j","article-title":"A gold\nnanocluster-based fluorescent probe for simultaneous pH and temperature\nsensing and its application to cellular imaging and logic gates","volume":"8","author":"Wu","year":"2016","journal-title":"Nanoscale"},{"key":"2026092109071396800_cit27","doi-asserted-by":"publisher","first-page":"8571","DOI":"10.1039\/c4cc03949a","article-title":"One-pot\nsynthesis of fluorescent\nBSA-Ce\/Au nanoclusters as ratiometric pH probes","volume":"50","author":"Chen","year":"2014","journal-title":"Chem. Commun."},{"key":"2026092109071396800_cit28","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1021\/acssensors.8b01130","article-title":"Self-Referenced Ratiometric\nDetection of Sulfatase Activity with Dual-Emissive Urease-Encapsulated\nGold Nanoclusters","volume":"4","author":"Deng","year":"2019","journal-title":"ACS Sens."},{"key":"2026092109071396800_cit29","doi-asserted-by":"publisher","first-page":"5333","DOI":"10.1021\/acs.analchem.5b00628","article-title":"Single Probe for Imaging\nand Biosensing of pH, Cu(2+) Ions, and pH\/Cu(2+) in Live Cells with\nRatiometric Fluorescence Signals","volume":"87","author":"Han","year":"2015","journal-title":"Anal. Chem."},{"key":"2026092109071396800_cit30","doi-asserted-by":"publisher","first-page":"17011","DOI":"10.1021\/ja308830e","article-title":"Ultra-small,\nhighly stable, and sensitive\ndual nanosensors for imaging intracellular oxygen and pH in cytosol","volume":"134","author":"Wang","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"2026092109071396800_cit31","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1039\/c5tb02071a","article-title":"Simultaneous\nimaging of intracellular pH and O2 using functionalized semiconducting\npolymer dots","volume":"4","author":"Xu","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"2026092109071396800_cit32","doi-asserted-by":"publisher","first-page":"18964","DOI":"10.1021\/jacs.9b11024","article-title":"Multifunctional Nanoscale Metal-Organic Layers for Ratiometric pH\nand Oxygen Sensing","volume":"141","author":"Lan","year":"2019","journal-title":"J. Am. Chem. Soc."},{"key":"2026092109071396800_cit33","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1016\/j.matlet.2005.04.024","article-title":"Synthesis\nand characterization of CdS\/BSA nanocomposites","volume":"59","author":"Liang","year":"2005","journal-title":"Mater. Lett."},{"key":"2026092109071396800_cit34","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.jallcom.2015.06.132","article-title":"Photoelectrolchemical\nperformance of PbS\/CdS quantum dots co-sensitized TiO2 nanosheets\narray film photoelectrodes","volume":"647","author":"Yao","year":"2015","journal-title":"J. Alloys Compd."},{"key":"2026092109071396800_cit35","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/nchem.2718","article-title":"Hypersensitive\ndual-function luminescence\nswitching of a silver-chalcogenolate cluster-based metal-organic framework","volume":"9","author":"Huang","year":"2017","journal-title":"Nat. Chem."},{"key":"2026092109071396800_cit36","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1021\/acssuschemeng.8b04124","article-title":"Synthesis of Luminescent\nGold Nanoclusters Embedded\nGoose Feathers for Facile Preparation of Au(I) Complexes with Aggregation-Induced\nEmission","volume":"7","author":"Shu","year":"2018","journal-title":"ACS Sustainable Chem. Eng."},{"key":"2026092109071396800_cit37","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1039\/c3nr06040c","article-title":"The role of protein\ncharacteristics in the formation and fluorescence\nof Au nanoclusters","volume":"6","author":"Xu","year":"2014","journal-title":"Nanoscale"},{"key":"2026092109071396800_cit38","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.foodchem.2018.03.138","article-title":"Characterization of food additive-potato starch complexes\nby FTIR and X-ray diffraction","volume":"260","author":"Dankar","year":"2018","journal-title":"Food Chem."},{"key":"2026092109071396800_cit39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bpc.2012.07.001","article-title":"The dityrosine cross-link\nas an intrinsic donor for assembling FRET pairs in the study of protein\nstructure","volume":"170","author":"Bystranowska","year":"2012","journal-title":"Biophys. Chem."},{"key":"2026092109071396800_cit40","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1016\/j.talanta.2010.10.047","article-title":"Ultrasensitive\ncysteine\nsensing using citrate-capped CdS quantum dots","volume":"83","author":"Wang","year":"2011","journal-title":"Talanta"},{"key":"2026092109071396800_cit41","doi-asserted-by":"publisher","first-page":"62","DOI":"10.3390\/antiox6030062","article-title":"Cysteine,\nGlutathione, and Thiol Redox Balance in Astrocytes","volume":"6","author":"McBean","year":"2017","journal-title":"Antioxidants"},{"key":"2026092109071396800_cit42","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1366\/0003702953965678","article-title":"Laser-Excited\nFluorescence of Dityrosine","volume":"49","author":"Mahmoud","year":"2016","journal-title":"Appl. Spectrosc."},{"key":"2026092109071396800_cit43","doi-asserted-by":"publisher","first-page":"6059","DOI":"10.1021\/acs.analchem.7b05405","article-title":"Electrocatalytic\nOxidation of Tris(2-carboxyethyl)phosphine at Pyrroloquinoline Quinone\nModified Carbon Nanotube through Single Nanoparticle Collision","volume":"90","author":"Patrice","year":"2018","journal-title":"Anal. Chem."},{"key":"2026092109071396800_cit44","doi-asserted-by":"publisher","first-page":"3990","DOI":"10.1167\/iovs.11-9321","article-title":"Redox proteomic\nidentification of visual arrestin dimerization in photoreceptor degeneration\nafter photic injury","volume":"53","author":"Lieven","year":"2012","journal-title":"Invest. Ophthalmol. Visual\nSci."},{"key":"2026092109071396800_cit45","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1021\/ja806804u","article-title":"Protein-directed\nsynthesis of highly\nfluorescent gold nanoclusters","volume":"131","author":"Xie","year":"2009","journal-title":"J. Am. Chem.\nSoc."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c00711","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/15\/8943\/67739638\/acsomega.0c00711.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/15\/8943\/67739638\/acsomega.0c00711.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:24:55Z","timestamp":1789997095000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/5\/15\/8943\/619292\/Rational-Design-of-Three-in-One-Ratiometric"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,9]]},"references-count":45,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,4,9]]},"published-print":{"date-parts":[[2020,4,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c00711","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,9]]}}}