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However, clinical trials in recent decades have disappointed in delivering notable progress. Herein, a microfluidic\u2010assisted synthetic hydrogen\u2010bond organic framework (HOF) as a polyamine\u2010depleting nanoplatforms designed to unleash the vigor of both dendritic cells (DCs) and T cells for precision cancer immunotherapy is reported. Upon internalization by tumor cells, the loaded plasma amine oxidase (PAO) in HOF efficiently depletes polyamines, remolding the tumor microenvironment and alleviating T\u2010cell immunosuppression. This process also generates acrolein and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , triggering CRISPR\u2010assisted neoantigen generation. Specifically, Acrolein induces carbonyl stress, increasing mutational burdens. Simultaneously, HOF leverages the energy from the bis[2,4,5\u2010trichloro\u20106\u2010(pentyloxycarbonyl)phenyl] oxalate (CPPO)\u2010H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    reaction for CRET\u2010triggered singlet oxygen production, leading to thioether bond cleavage and release CRISPR\u2010Cas9. Once released, CRISPR\u2010Cas9 knocks out the DNA mismatch repair (MMR)\u2010related MLH1 gene, further elevating mutational burdens and generating neoantigens, ideal targets for DCs. This dual\u2010action strategy not only corrects T\u2010cell immunosuppression but also enhances DC efficacy, presenting a powerful approach for tumor immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.202411886","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:42:37Z","timestamp":1740012157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Polyamine\u2010Depleting Hydrogen\u2010Bond Organic Frameworks Unleash Dendritic Cell and T Cell Vigor for Targeted CRISPR\/Cas\u2010Assisted Cancer Immunotherapy"],"prefix":"10.1002","volume":"37","author":[{"given":"Yongchun","family":"Pan","sequence":"first","affiliation":[{"name":"College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life Science National Laboratory of Solid State Microstructures Nanjing University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life Science National Laboratory of Solid State Microstructures Nanjing University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Luan","sequence":"additional","affiliation":[{"name":"College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life Science National Laboratory of Solid State Microstructures Nanjing University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanzhong","family":"He","sequence":"additional","affiliation":[{"name":"College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life Science National Laboratory of Solid State Microstructures Nanjing University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shurong","family":"Qin","sequence":"additional","affiliation":[{"name":"College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life Science National Laboratory of Solid State Microstructures Nanjing University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianglan","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life Science National Laboratory of Solid State Microstructures Nanjing University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangshun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Nanjing First Hospital Nanjing Medical University  Nanjing 210006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Han","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; 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