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They typically adopt an M2\u2010like phenotype that promotes tumor progression by providing survival signals, suppressing anti\u2010tumor immunity, and facilitating pre\u2010metastatic niche formation. Reprogramming TAMs toward an anti\u2010tumor phenotype has emerged as a promising therapeutic strategy, with the repolarization of M2\u2010like TAMs into an M1\u2010like phenotype being central to this approach. Here, a nitric oxide (NO)\u2010activatable near\u2010infrared\u2010II (NIR\u2010II) fluorescence\/photoacoustic nanoinducer (I\/E@M2pep) that selectively targets M2\u2010like TAMs and reprograms them toward an M1\u2010like phenotype, thereby enhancing anti\u2010tumor efficacy is reported. In this construct, the M2pep peptide enables M2\u2010like TAM targeting, IPI549 reprograms them toward an M1\u2010like phenotype while inducing NO production, and the NO\u2010activatable NIR\u2010II probe (ETNO) allows for in vivo visualization of macrophage repolarization via NIR\u2010II fluorescence\/photoacoustic imaging. In a mouse breast cancer model, intravenous administration of I\/E@M2pep produced a ratiometric NIR\u2010II photoacoustic signal change that correlated with M2\u2010to\u2010M1 repolarization. Furthermore, combining this nanoinducer with a CD47 monoclonal antibody markedly enhanced anti\u2010tumor immunity through M1 macrophage\u2010mediated tumor killing and TME remodeling. This work presents an effective in vivo strategy that simultaneously facilitates and visualizes TAM repolarization, holding promise for broader applications in studying tumor initiation, metastasis, and treatment response.<\/jats:p>","DOI":"10.1002\/advs.202524367","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:43:02Z","timestamp":1773157382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Real\u2010Time In Vivo Visualization of Tumor\u2010Associated Macrophage Reprogramming Using a Nitric Oxide\u2010Activatable NIR\u2010II Nanoinducer"],"prefix":"10.1002","volume":"13","author":[{"given":"Qian","family":"Chen","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Nano\u2010Bio Interface, Suzhou Key Laboratory of Functional Molecular Imaging Technology, Division of Nanobiomedicine and i\u2010Lab Suzhou Institute of Nano\u2010Tech and Nano\u2010Bionics Chinese 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