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To overcome the limitations of conventional monotargeting approaches, we developed a light-gated DNA nanoclaw machine (L-DNM) that integrates high-specificity recognition, spatiotemporally controlled therapy, and real-time monitoring of molecular activation within a unified nanoplatform. The L-DNM employed a multivalent targeting mechanism directed against a triple-marker signature, epithelial cell adhesion molecule (EpCAM), MUC1, and nucleolin (NCL), achieving exceptional targeting accuracy toward MCF-7 human breast cancer cells even in heterogeneous environments. Its novel photocleavable aptamer design ensures that the Met-inhibiting function remains biologically inert until activated by UV irradiation. This strategy enables precise spatiotemporal control over receptor tyrosine kinase (RTK) inhibition with minimal off-target effects. Furthermore, the system couples therapeutic activation with instantaneous electrochemiluminescence (ECL) reporting, transforming molecular recognition events into quantifiable signals with high signal-to-noise ratio in complex matrices. By unifying multiplexed targeting, light-gated activation, and self-reporting capability, the L-DNM platform represents a transformative shift from conventional therapeutics to adaptive, intelligent theranostic systems.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c03110","type":"journal-article","created":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T14:01:53Z","timestamp":1786284113000},"page":"24366-24378","source":"Crossref","is-referenced-by-count":0,"title":["A Light-Controlled\nDNA Nanoclaw Machine: Integrated\nMultiplexed Recognition, Spatiotemporally Programmable Therapy, and\nReal-Time Electrochemical Signaling for Precision Receptor Regulation"],"prefix":"10.1021","volume":"98","author":[{"given":"Xia","family":"Liu","sequence":"first","affiliation":[{"name":"Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710061"]},{"name":"Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis , ,","place":["Xi\u2019an, China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710061"]},{"name":"Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis , ,","place":["Xi\u2019an, China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxi","family":"Xia","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710061"]},{"name":"Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis , ,","place":["Xi\u2019an, China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710061"]},{"name":"Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis , ,","place":["Xi\u2019an, China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabo","family":"Wang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710061"]},{"name":"Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis , ,","place":["Xi\u2019an, China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusi","family":"Bu","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710061"]},{"name":"Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis , ,","place":["Xi\u2019an, China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3936-3565","authenticated-orcid":true,"given":"Xiaoyu","family":"Xie","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710061"]},{"name":"Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis , ,","place":["Xi\u2019an, China, 710061"]},{"name":"Key Laboratory of Environment and Genes Related to Diseases, Xi\u2019an Jiaotong University, Ministry of Education , ,","place":["Xi\u2019an, China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"issue":"36","key":"2026083118454909800_cit1","doi-asserted-by":"publisher","first-page":"25383","DOI":"10.1021\/jacs.4c10710","article-title":"Regulation\nof cell membrane potential through supramolecular system for activating\ncalcium ion channels","volume":"146","author":"Song","year":"2024","journal-title":"J. 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