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However, under physiological conditions, their performance is often hindered by insufficient endogenous driving forces, nuclease degradation, and lysosomal entrapment. In this study, we develop a protein corona (PC)\u2010armored DNA nanomachine with spatiotemporal control for multiple intracellular biomarker imaging. By pre\u2010assembling a UV\u2010responsive PC shell, the DNA nanomachine forms a physical barrier that protects nucleic acids from nucleases, reduces uncontrollable PC formation during unimpaired operation, and enhances cellular uptake via PC\u2010mediated targeting. After internalization, the retained PC promotes lysosomal escape, followed by light\u2010triggered disassembly for precise cytoplasmic operation of the nanomachine. Notably, our nanomachine employs RNA as a track and the widely expressed intracellular RNase H enzyme as the driving force, circumventing sequence limitations and establishing a general operational platform. Through this modulation, we achieve in situ imaging of microRNA in U87 human glioblastoma cells and ATP in A549 lung carcinoma cells, pioneering a PC\u2010enabled paradigm for DNA nanomachines and building a versatile intracellular diagnostic platform for precision medicine.<\/jats:p>","DOI":"10.1002\/anie.202516456","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T08:14:55Z","timestamp":1760084095000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Spatiotemporally Controlled Protein Corona\u2010Armored DNA Nanomachine for Multitype Biomarker Imaging in Living Cells"],"prefix":"10.1002","volume":"64","author":[{"given":"Ziqi","family":"Xu","sequence":"first","affiliation":[{"name":"Collaborative Innovation Center of Biomedical Functional Materials and Key Laboratory of Biofunctional Materials of Jiangsu Province School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Biomedical Functional Materials and Key Laboratory of Biofunctional Materials of Jiangsu Province School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Guo","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Biomedical Functional Materials and Key Laboratory of Biofunctional Materials of Jiangsu Province School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiling","family":"Li","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Biomedical Functional Materials and Key Laboratory of Biofunctional Materials of Jiangsu Province School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Li","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Biomedical Functional Materials and Key Laboratory of Biofunctional Materials of Jiangsu Province School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Molecular Recognition and Biosensing Shanghai Engineering Research Center of Organ Repair Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education) School of Life Sciences Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7608-8844","authenticated-orcid":false,"given":"Zhaoyin","family":"Wang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Biomedical Functional Materials and Key Laboratory of Biofunctional Materials of Jiangsu Province School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"},{"name":"State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical Engineering Nanjing University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202200327"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1cs15005g"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201611777"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202312665"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00580"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c09855"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202302542"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202406599"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202116932"},{"key":"e_1_2_7_10_1","first-page":"21234","volume":"63","author":"Wang J.","year":"2024","journal-title":"Angew. 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