{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:43:41Z","timestamp":1792784621271,"version":"4.5.0"},"reference-count":38,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LMS25B050002"],"award-info":[{"award-number":["LMS25B050002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LTGC24B050002"],"award-info":[{"award-number":["LTGC24B050002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["22404147"],"award-info":[{"award-number":["22404147"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["82405023"],"award-info":[{"award-number":["82405023"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cisplatin-based chemotherapy remains an attractive alternative for controlling advanced cancers. However, a subset of cancer patients exhibits resistance to cisplatin. Accurate and early prediction of individual responses to cisplatin treatment is critical to personalized medicine guidance. The development of an effective method to predict chemotherapy response in cancer patients still faces challenges. Based on extracellular lactate, a key indicator of cisplatin resistance, herein, we report a multivariate-activated DNA logic gate to achieve lactate imaging with high fidelity. This device is assembled by a PNA\u2013peptide\u2013PNA copolymer and a lactate-specific aptamer with a cell membrane-anchoring aptamer module. It operates in response to the matrix metalloproteinase in the tumor microenvironment (TME) after the device anchors to nucleolin; thereby, the liberated aptamer binds to lactate through structure switching, achieving \u201coff\u2013on\u201d fluorescence imaging. Additionally, imaging characteristics in combination with the Logistic Regression algorithm enable noninvasive prediction of cancer responses to cisplatin-based chemotherapy. In 90 cisplatin-resistant tumor-bearing mice, this detection model effectively identifies 77 of the 90 samples, showing a satisfactory accuracy of 85.6%. We further monitor the lactate level decreases in the TME using our method after the drug-resistant tumor-bearing mice treatment by stiripentol and successfully predict the enhancement of the therapeutic effect and the extension of the survival period. This study highlights the combined power of the DNA logic gate and machine learning for the analysis of lactate, paving the way for clinical cisplatin resistance detection and facilitating the formulation of personalized medicine guidance.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c04574","type":"journal-article","created":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T15:01:23Z","timestamp":1788706883000},"page":"27181-27194","source":"Crossref","is-referenced-by-count":0,"title":["Multivariate-Activated\nDNA Logic Gate for Predicting\nResponses to Cisplatin-Based Chemotherapy"],"prefix":"10.1021","volume":"98","author":[{"given":"Bin","family":"Li","sequence":"first","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jueyue","family":"Yan","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueling","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College , ,","place":["Hangzhou, China, 310013"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingcong","family":"Fan","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9115-4571","authenticated-orcid":true,"given":"Jiayi","family":"Yin","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5944-9940","authenticated-orcid":true,"given":"Yaokun","family":"Xia","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310003"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"issue":"7","key":"2026091511080906600_cit1","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1038\/s41588-025-02233-y","article-title":"Predicting\nresistance to chemotherapy using chromosomal instability signatures","volume":"57","author":"Thompson","year":"2025","journal-title":"Nat. Genet."},{"issue":"12","key":"2026091511080906600_cit2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adz7615","article-title":"Transforming\ncisplatin into targeted\nphotothermal chemotherapeutics through the platinum-phosphate coordination\nwithin a hyaluronan nanogel","volume":"12","author":"Zhang","year":"2026","journal-title":"Sci. Adv."},{"issue":"13","key":"2026091511080906600_cit3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2510265123","article-title":"Targeting the ANGPTL4\/NRP1\/ABL1\/RAD51\naxis reverses\ncisplatin resistance by impairing DNA damage repair in head and neck\ncancer","volume":"123","author":"Asiedu","year":"2026","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"1","key":"2026091511080906600_cit4","doi-asserted-by":"publisher","first-page":"e34","DOI":"10.1016\/S1470-2045(24)00395-4","article-title":"Advances and\nchallenges in precision imaging","volume":"26","author":"Hricak","year":"2025","journal-title":"Lancet Oncol."},{"issue":"2","key":"2026091511080906600_cit5","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1021\/acs.jproteome.5c00771","article-title":"Toward Proteomic-Based Prediction of Ex Vivo Platinum\nSensitivity in Ovarian Cancer Ascitic Cellular Aggregates: A Pilot\nStudy","volume":"25","author":"Scanlan","year":"2026","journal-title":"J. Proteome. Res."},{"issue":"8104","key":"2026091511080906600_cit6","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/s41586-025-09985-x","article-title":"Critical role\nfor a high-plasticity cell state in lung\ncancer","volume":"651","author":"Chan","year":"2026","journal-title":"Nature"},{"key":"2026091511080906600_cit7","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.216837","article-title":"The emerging role of lactate in tumor\nmicroenvironment and its clinical relevance","volume":"590","author":"Chen","year":"2024","journal-title":"Cancer Lett."},{"issue":"11","key":"2026091511080906600_cit8","doi-asserted-by":"publisher","first-page":"2992","DOI":"10.1016\/j.cell.2025.03.048","article-title":"Long-term histone\nlactylation connects metabolic and epigenetic rewiring in innate immune\nmemory","volume":"188","author":"Ziogas","year":"2025","journal-title":"Cell"},{"issue":"4","key":"2026091511080906600_cit9","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1038\/s41589-025-02107-8","article-title":"GCN5-ERK lactylation-phosphorylation\nloop amplifies lactate-driven cancer progression","volume":"22","author":"Huang","year":"2026","journal-title":"Nat. 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Rev. Immunol."},{"key":"2026091511080906600_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101059","article-title":"Single-cell transcriptome analysis\nreveals the association between histone lactylation and cisplatin\nresistance in bladder cancer","volume":"73","author":"Li","year":"2024","journal-title":"Drug Resistance\nUpdates"},{"issue":"8021","key":"2026091511080906600_cit15","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/s41586-024-07620-9","article-title":"NBS1 lactylation is\nrequired for efficient DNA repair and chemotherapy resistance","volume":"631","author":"Chen","year":"2024","journal-title":"Nature"},{"issue":"3","key":"2026091511080906600_cit16","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ady5324","article-title":"Lactate derived\nfrom cancer-associated fibroblasts\npromotes alternative splicing and castration resistance in prostate\ncancer","volume":"12","author":"Zhao","year":"2026","journal-title":"Sci. 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Chem.,\nInt. Ed."},{"issue":"10","key":"2026091511080906600_cit24","doi-asserted-by":"publisher","first-page":"7515","DOI":"10.1021\/acs.analchem.5c07149","article-title":"D-Lactate SELEX Yielding Aptamers\nBinding Stronger to L-Lactate: Implication of Intrinsic Chiral Preference","volume":"98","author":"Zia","year":"2026","journal-title":"Anal. Chem."},{"issue":"43","key":"2026091511080906600_cit25","doi-asserted-by":"publisher","first-page":"24050","DOI":"10.1021\/acs.analchem.5c04270","article-title":"Centipede-Mimetic\nDNA Nanomachines with Circular Sensing Modules for Spatial Monitoring\nof Extracellular Metabolites","volume":"97","author":"Guo","year":"2025","journal-title":"Anal. Chem."},{"issue":"3","key":"2026091511080906600_cit26","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1039\/D2CS00479H","article-title":"Engineering lactate-modulating nanomedicines\nfor cancer therapy","volume":"52","author":"Chen","year":"2023","journal-title":"Chem. Soc. Rev."},{"key":"2026091511080906600_cit27","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.canlet.2017.06.001","article-title":"Feedback regulation\nof ALDOA activates the HIF-1\u03b1\/MMP9 axis to promote lung cancer\nprogression","volume":"403","author":"Chang","year":"2017","journal-title":"Cancer Lett."},{"key":"2026091511080906600_cit28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1549276","article-title":"Research progress of\nHIF-1\u03b1 on immunotherapy outcomes in immune vascular microenvironment","volume":"16","author":"Shi","year":"2025","journal-title":"Front. Immunol."},{"issue":"14","key":"2026091511080906600_cit29","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202500174","article-title":"Drug Delivery Platform Targeting MMP9 in Combination\nwith Photothermal Therapy to Improve Tumor Chemosensitivity","volume":"14","author":"Fu","year":"2025","journal-title":"Adv. Healthcare Mater."},{"issue":"9","key":"2026091511080906600_cit30","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41568-025-00848-1","article-title":"Metabolic adaptations of brain metastasis","volume":"25","author":"Parida","year":"2025","journal-title":"Nat. Rev. Cancer"},{"issue":"4","key":"2026091511080906600_cit31","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202111836","article-title":"A Multivariate-Gated\nDNA Nanodevice for Spatioselective Imaging of Pro-metastatic Targets\nin Extracellular Microenvironment","volume":"61","author":"Xiang","year":"2022","journal-title":"Angew. Chem.,\nInt. Ed."},{"issue":"1","key":"2026091511080906600_cit32","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-026-04125-7","article-title":"Core-shell\nmicroneedles with MMP\/pH-triggered release for periodontitis bone\nrepair","volume":"24","author":"Liu","year":"2026","journal-title":"J. Nanobiotechnol."},{"issue":"46","key":"2026091511080906600_cit33","doi-asserted-by":"publisher","first-page":"25782","DOI":"10.1021\/acs.analchem.5c05375","article-title":"Entropy-Driven Nucleic\nAcid Amplifier Based on Spatial\nConfinement as a \u2033Booster\u2033 for Detection of Extracellular\nVesicle MicroRNAs to Diagnose Gastric Cancer and Monitor Therapeutic\nResponse","volume":"97","author":"Xia","year":"2025","journal-title":"Anal. Chem."},{"key":"2026091511080906600_cit34","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121078","article-title":"Transformable\namyloid-beta mimetic\npeptide amphiphiles for lysosomal disruption in non-small cell lung\ncancer","volume":"277","author":"Baehr","year":"2021","journal-title":"Biomaterials"},{"issue":"3","key":"2026091511080906600_cit35","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202514789","article-title":"From Spark to Flame: ROS- and Light-Cascade\nActivatable NIR-II AIE Probe for Precise Tumor Imaging and Self-Amplifying\nPhototherapy","volume":"13","author":"Chen","year":"2026","journal-title":"Adv. Sci."},{"key":"2026091511080906600_cit36","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2024.117613","article-title":"Empowerment of AI algorithms\nin biochemical sensors","volume":"173","author":"Zhou","year":"2024","journal-title":"TrAC Trend. Anal. 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Today Bio."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c04574","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/27181\/68396103\/acs.analchem.6c04574.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/27181\/68396103\/acs.analchem.6c04574.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:52:10Z","timestamp":1789487530000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/36\/27181\/5421903\/Multivariate-Activated-DNA-Logic-Gate-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,6]]},"references-count":38,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,9,6]]},"published-print":{"date-parts":[[2026,9,15]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c04574","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,6]]}}}