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Here, we report apurinic\/apyrimidinic endonuclease 1 (APE1)\u2010triggered inhalable microsphere (ATIM) for non\u2010small cell lung cancer (NSCLC) theranostics by leveraging inhalation delivery and homotypic targeting to accelerate the local enrichment of DNA tetrahedrons (TDNs) in pulmonary tumors, which enables in situ NSCLC theranostics. Upon intracellular recognition of the APE1, entropy\u2010driven catalytic circuits are activated, triggering nanoparticle aggregation to amplify fluorescence for real\u2010time tumor imaging and releasing miR\u2010126\u20103p to induce tumor cell apoptosis by suppressing ADAM9. In a mouse orthotopic NSCLC model, the tumor\u2010bearing group showed a fluorescent intensity 1.67\u2010fold higher than the healthy group, and the pulmonary accumulation of the ATIM system via inhalation was 3.12\u2010fold higher than that via intravenous injection, while ATIM therapy significantly reduced the tumor burden to a relative area of 45.3 \u00b1 1.6%. Our results demonstrate that ATIM achieves accurate discrimination between benign and malignant pulmonary nodules while effectively inducing apoptosis in tumor cells. This theranostic system offers a promising dual\u2010functional platform for precision diagnosis and targeted therapy in early\u2010stage NSCLC.<\/jats:p>","DOI":"10.1002\/adma.202520216","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:43:10Z","timestamp":1777444990000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["APE1\u2010Triggered Inhalable Microsphere (ATIM) for In Situ Non\u2010Small Cell Lung Cancer Theranostics"],"prefix":"10.1002","volume":"38","author":[{"given":"Xinlin","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Chongqing Center for Clinical Laboratory Chongqing Academy of Medical Sciences Chongqing General Hospital School of Medicine Chongqing University  Chongqing 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