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This study presents an innate immunity\u2010guided, macrophage (M\u03a6)\u2010homing nanoplatform that enables oral delivery of theranostic agents to PDAC lesions by harnessing the migratory behavior of endogenous M\u03a6 toward tumor\u2010derived immune cues. The nanoplatform integrates a \u03b2Glus\u2010R848 prodrug\u2014constructed by conjugating \u03b2\u2010glucans (\u03b2Glus) with the immunomodulator resiquimod (R848) via a reactive oxygen species (ROS)\u2010responsive thioketal linker\u2014and Ag\n                    <jats:sub>2<\/jats:sub>\n                    Te quantum dots (QDs) for near\u2010infrared II (NIR\u2010II) imaging, forming \u03b2Glus\u2010R848\/Ag\n                    <jats:sub>2<\/jats:sub>\n                    Te nanoparticles (NPs). Upon oral administration, \u03b2Glus facilitates the selective uptake of NPs by intestinal M\u03a6 (\u03b2Glus\u2010R848\/Ag\n                    <jats:sub>2<\/jats:sub>\n                    Te NPs@M\u03a6), which subsequently migrate to the tumor microenvironment (TME). There, elevated ROS levels trigger the release of R848, reprogramming tumor\u2010associated M\u03a6 from an immunosuppressive M2 to an immunoactive M1 phenotype. This immune activation remodels the stroma, enhances T cell infiltration, and transforms the TME into an immunoactive state, thereby improving therapeutic outcomes. Concurrently, Ag\n                    <jats:sub>2<\/jats:sub>\n                    Te QDs enable deep\u2010tissue NIR\u2010II imaging for real\u2010time visualization of PDAC progression, liver metastasis, and treatment response. Guided by innate immune signals, this M\u03a6\u2010homing theranostic platform offers a promising strategy to overcome current challenges in PDAC treatment by integrating targeted immunotherapy with noninvasive, real\u2010time disease monitoring.\n                  <\/jats:p>","DOI":"10.1002\/adma.202507607","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T07:45:38Z","timestamp":1753083938000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Innate Immunity\u2010Guided Macrophage\u2010Homing Nanoplatform for Oral Tumor Immunotherapy and Real\u2010Time Deep\u2010Tissue Imaging in Pre\u2010Clinical Models"],"prefix":"10.1002","volume":"37","author":[{"given":"Putry Yosefa","family":"Siboro","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering National Tsing Hua University  Hsinchu 30013 Taiwan 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