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However, simultaneous targeted enrichment and controllable immunological activation of these macrophages at the tumor site remains challenging. As a solution, macrophages loaded with an advanced nanoparticle encapsulating CpG\u2010conjugated magnetic nanoclusters (MNC) with indocyanine green (ICG) and nigericin (NIG) (MNC\u2010ICG\u2010NIG@SiO<jats:sub>2<\/jats:sub> (MINS)), utilizing Se\u2500Se bond\u2010modified SiO<jats:sub>2<\/jats:sub>, are designed and applied in bladder cancer, which is typically managed surgically, followed by Bacillus Calmette\u2013Guerin (BCG) adjuvant instillation therapy. Upon intravenous administration, BCG\u2010mediated tumor\u2010localized inflammation leads to targeted accumulation of MINS@M\u03a6. MINS@M\u03a6 accumulates within the tumor tissue and is immunologically activated through laser irradiation, leading to ICG\u2010mediated generation of reactive oxygen species, Se\u2500Se bond cleavage, and subsequent NIG release to induce self\u2010pyroptosis. Consequently, MINS@M\u03a6 releases Fe<jats:sup>2+<\/jats:sup> ions and CpG, thus promoting the M1 polarization of tumor\u2010associated macrophages and secretion of appropriate antitumor cytokines. However, without intervention, MINS@M\u03a6 undergoes apoptosis in the bloodstream after 48\u00a0h without eliciting any immune response. Therefore, this innovative approach optimizes and enhances the efficacy of BCG immunotherapy by precisely modulating the cytokines for effective bladder cancer treatment without inducing a systemic inflammatory response.<\/jats:p>","DOI":"10.1002\/smll.202306699","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T03:38:02Z","timestamp":1700019482000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Engineered Macrophages Tune Intratumoral Cytokines through Precisely Controlled Self\u2010Pyroptosis to Enhance Bladder Cancer Immunotherapy"],"prefix":"10.1002","volume":"20","author":[{"given":"Pengyu","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Urology Harbin Medical University Cancer Hospital  Harbin 150081 China"},{"name":"NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Harbin Medical University  Harbin 150001 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