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However, their systemic administration is severely limited due to the off\u2010target toxicity. Here, this work describes a sequential drug delivery strategy. The formulation is composed of two sequential modules: a tumor microenvironment remodeling nanocarrier (poly(\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glutamic acid)\u2010\n                    <jats:italic>graft\u2010<\/jats:italic>\n                    methoxy poly(ethylene glycol)\/combretastatin A4, termed CA4\u2010NPs) and an immunotherapy nanocarrier (apcitide peptide\u2010decorated poly(\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glutamic acid)\u2010\n                    <jats:italic>graft<\/jats:italic>\n                    \u2010IMDQ\u2010N\n                    <jats:sub>3<\/jats:sub>\n                    conjugate, termed apcitide\u2010PLG\u2010IMDQ\u2010N\n                    <jats:sub>3<\/jats:sub>\n                    ). CA4\u2010NPs, as a vascular disrupting agent, are utilized to remodel the tumor microenvironment for enhancing tumor coagulation and hypoxia. Subsequently, the apcitide\u2010PLG\u2010IMDQ\u2010N\n                    <jats:sub>3<\/jats:sub>\n                    could identify and target tumor coagulation through the binding of surface apcitide peptide to the GPIIb\u2010IIIa on activated platelets. Afterward, IMDQ is activated selectively through the conversion of \u201c\u2010N\n                    <jats:sub>3<\/jats:sub>\n                    \u201d to \u201c\u2010NH\n                    <jats:sub>2<\/jats:sub>\n                    \u201d in the presence of hypoxia. The biodistribution results confirm their high tumor uptake of activated IMDQ (22.66%ID\/g). By augmenting the priming and immunologic memory of tumor\u2010specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, 4T1 and CT26 tumors with a size of \u2248500 mm\n                    <jats:sup>3<\/jats:sup>\n                    are eradicated without recurrence in mouse models.\n                  <\/jats:p>","DOI":"10.1002\/adma.202312493","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T01:54:45Z","timestamp":1709690085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Tumor Microenvironment Remodeling\u2010Mediated Sequential Drug Delivery Potentiates Treatment Efficacy"],"prefix":"10.1002","volume":"36","author":[{"given":"Yajun","family":"Xu","sequence":"first","affiliation":[{"name":"Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun 130022 China"},{"name":"School of Applied Chemistry and Engineering University of Science and Technology of China  Hefei 230026 China"},{"name":"Jilin Biomedical Polymers Engineering Laboratory  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun 130022 China"},{"name":"School of Applied Chemistry and Engineering University of Science and Technology of China  Hefei 230026 China"},{"name":"Jilin Biomedical Polymers Engineering Laboratory  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyao","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321037 China"},{"name":"Key Laboratory for Advanced Drug Delivery Systems of Zhejiang Provincial College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321037 China"},{"name":"Key Laboratory for Advanced Drug Delivery Systems of Zhejiang Provincial College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun 130022 China"},{"name":"School of Applied Chemistry and Engineering University of Science and Technology of China  Hefei 230026 China"},{"name":"Jilin Biomedical Polymers Engineering Laboratory  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoying","family":"Kong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun 130022 China"},{"name":"School of Applied Chemistry and Engineering University of Science and Technology of China  Hefei 230026 China"},{"name":"Jilin Biomedical Polymers Engineering Laboratory  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanran","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun 130022 China"},{"name":"School of Applied Chemistry and Engineering University of Science and Technology of China  Hefei 230026 China"},{"name":"Jilin Biomedical Polymers Engineering Laboratory  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun 130022 China"},{"name":"Jilin Biomedical Polymers Engineering Laboratory  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2947-4456","authenticated-orcid":false,"given":"Zhen","family":"Gu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321037 China"},{"name":"Key Laboratory for Advanced Drug Delivery Systems of Zhejiang Provincial College of 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