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Among these, reprogramming of the tumor immunosuppressive microenvironment is a promising strategy to enhance the efficacy of tumor immunotherapy. The CRISPR\/Cas9 system\u2010based gene editing further offers a viable approach for precise regulation of endogenous gene expression associated with tumor immunosuppression. Current delivery vectors face a trilemma between biosafety profiles, expansion capacity, and targeting accuracy. To this end, we developed a triple\u2010modality therapeutic platform, termed TriCON (Triple Convergent Oncology Nanotherapy), characterized by three core mechanistic attributes: spatiotemporal convergence, stimuli\u2010responsive controllability, and tumor\u2010microenvironment modulatory conductivity. This orchestrated combination of rationally designed gene editing (targeting poliovirus receptor), nano\u2010encapsulated doxorubicin (DOX) chemotherapy, and checkpoint blockade immunotherapy demonstrated enhanced synergistic antitumor activity in pancreatic ductal adenocarcinoma (PDAC) models, achieving tumor regression through enhanced chemotherapy, immunogenic cell death induction, and natural killer (NK) cells activation. The platform achieved superior in vivo gene editing (14.2% PVR editing efficiency) via optimized endosomal escape and CRISPR system release. This triaxial approach establishes a programmable nanotherapeutic paradigm that synergizes gene editing precision with chemo\u2010immunotherapy, offering a novel framework for PDAC treatment.<\/jats:p>","DOI":"10.1002\/advs.202512978","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T04:02:37Z","timestamp":1768795357000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TriCON: A Carbon\u2010Based Triple\u2010Modal Nanoplatform for Pancreatic Cancer Therapy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8751-5116","authenticated-orcid":false,"given":"Xinyu","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery General Surgery Center The First Hospital of Jilin University Changchun P. R. 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