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Here, we find that regorafenib (REG) and paclitaxel (PTX) exhibit robust synergistic cytotoxicity against tumor cells, while also potentiating repolarization of macrophages from pro\u2011tumor M2 to antitumor M1 phenotype. To leverage this synergy and improve the therapeutic efficacy of albumin\u2010bound PTX in mCRC, we construct an albumin nanoparticle co\u2010loaded with REG and PTX (Alb\u2010RP). Alb\u2010RP facilitates macrophage phenotypic transition to the M1 state and upregulates proinflammatory cytokine expression, exhibiting potent tumoricidal activity in macrophage\u2010tumor cell co\u2010culture systems. In the MC38 colorectal peritoneal metastasis (CPM) model, Alb\u2010RP markedly suppresses tumor progression and prolongs survival, achieving complete tumor regression in 44% of treated mice. Meanwhile, Alb\u2010RP effectively reshapes the immune microenvironment in both peritoneal fluid and tumor tissues, characterized by decreased M2 macrophages, expanded M1 macrophages, enhanced dendritic cell activation, and increased infiltration of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Collectively, this study presents a translatable albumin\u2010based co\u2010delivery strategy that integrates direct chemotherapeutic cytotoxicity and macrophage repolarization to overcome the limited efficacy of albumin\u2010bound PTX against mCRC.\n                  <\/jats:p>","DOI":"10.1002\/smtd.71021","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:28:47Z","timestamp":1788776927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Albumin Nanoparticle\u2013Mediated Codelivery of Regorafenib and Paclitaxel Boosts Chemoimmunotherapy of Peritoneal Metastases"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5192-2975","authenticated-orcid":false,"given":"Meng\u2010Ting","family":"Lin","sequence":"first","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou 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