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Current improvements primarily focus on optimizing biomimetic coatings to enhance capture efficiency, but there remains a significant gap between existing strategies and the practical demands of CTCs detection. Herein, a novel method considering the perspective of tumor cell modification was proposed, which involved concurrently modulating cellular chemical and mechanical properties. Specifically, the strategy employed metabolic glycoengineering to selectively remold tumor cells, thereby introducing artificial receptors into the tumor cell membrane. Additionally, Cytochalasin D, a drug that can interfere with the cytoskeleton, was used to alter the mechanical properties of the cell membrane, softening it and thereby significantly enhancing the contact area and adhesion ability between target cells and the substrate surface. To cope with the complex application environment, a visual biomimetic detection system was developed, leveraging the homologous targeting properties of the tumor cell biomimetic layer in combination with advanced colorimetric nanoprobes, enabling highly sensitive and specific detection of engineered CTCs. Overall, this approach adeptly circumvents challenges associated with biomarker bias, offering a robust method for non\u2010invasive cancer diagnostics.<\/jats:p>","DOI":"10.1002\/adhm.202505535","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T09:21:22Z","timestamp":1769592082000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chemical and Mechanical Synergistic Modulation for Engineered Tumor Cells Enables High\u2010Performance Biomimetic Detection of Circulating Tumor Cells"],"prefix":"10.1002","volume":"15","author":[{"given":"Lanlan","family":"Jia","sequence":"first","affiliation":[{"name":"School of Pharmacy Health Science Center Xi'an Jiaotong University  Xi'an China"},{"name":"Shaanxi Engineering Research Center of Cardiovascular Drugs Screening &amp; Analysis Xi'an 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