{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:07:02Z","timestamp":1789632422556,"version":"build-2803163510"},"reference-count":45,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"name":"the Heilongjiang Provincial Excellent Young Teachers Basic Research Support Program","award":["YQJH2025244"],"award-info":[{"award-number":["YQJH2025244"]}]},{"name":"National College Student Innovation and Entrepreneurship Training Program","award":["202410222018"],"award-info":[{"award-number":["202410222018"]}]},{"name":"the Heilongjiang Provincial Key Laboratory of New Drug Development and Pharmacotoxicological Evaluation","award":["kfkt2025-19"],"award-info":[{"award-number":["kfkt2025-19"]}]},{"name":"the Heilongjiang Province Higher Education Excellent Innovation Team Basic Research Fund","award":["2023-KYYWF-0640"],"award-info":[{"award-number":["2023-KYYWF-0640"]}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Biomater Res"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:p>\n                    The management of colorectal cancer is constrained by a self-perpetuating vicious cycle, driven initially by gut microbiota dysbiosis that triggers chronic inflammation, which in turn promotes the establishment of an immunosuppressive tumor microenvironment and multidrug resistance. We engineered a glutathione (GSH)-responsive prodrug micellar nanosystem (PSC\/PTX) for the synergistic co-delivery of paclitaxel (PTX) and curcumin (CUR). In this nanoplatform, CUR was covalently conjugated to form a prodrug via disulfide linkages, while PTX was physically encapsulated within the micelles, ensuring the precise release of the 2 drugs in the tumor-specific microenvironment. The nanoplatform reverses P-glycoprotein-mediated drug efflux, prolongs the circulation time, improves the bioavailability, and enhances the accumulation at tumor sites of 2 drugs. This nanoplatform exerts multifaceted therapeutic efficacy. Initially, it reinstates the balance of intestinal microbiota by increasing the abundances of beneficial microorganisms (e.g.,\n                    <jats:italic toggle=\"yes\">Bacteroidetes<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Eubacterium<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Bifidobacterium<\/jats:italic>\n                    ) while decreasing those of harmful bacteria (e.g.,\n                    <jats:italic toggle=\"yes\">Bacteroides fragilis<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    ). Additionally, it inhibits pro-tumor inflammatory factors by attenuating the levels of interleukin-6 (IL-6) and tumor necrosis factor-\u03b1 (TNF-\u03b1), ultimately leading to a remodeling of the immunosuppressive tumor microenvironment (TME). This process involves boosting the infiltration of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, decreasing the number of immunosuppressive regulatory T cells (Tregs), and repolarizing macrophages to the M1 phenotype (CD86\n                    <jats:sup>+<\/jats:sup>\n                    \u2191, CD206\n                    <jats:sup>+<\/jats:sup>\n                    \u2193). Collectively, this integrated and coordinated strategy breaks the self-sustaining vicious cycle of microbiota-driven, inflammation-fueled carcinogenesis and multidrug resistance via the synergistic modulation of chemotherapy sensitization, immunity, and the microbiota, thereby offering a novel and promising therapeutic modality for refractory colorectal cancer.\n                  <\/jats:p>","DOI":"10.34133\/bmr.0399","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:50:05Z","timestamp":1787673005000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["A Glutathione-Responsive Prodrug Nanosystem for Colorectal Cancer: Synergistic Co-Delivery of Paclitaxel and Curcumin to Combat Multidrug Resistance and Reinvent the Immunosuppressive Microenvironment"],"prefix":"10.34133","volume":"30","author":[{"given":"Yu","family":"Qiao","sequence":"first","affiliation":[{"name":"College of Pharmacy, \rJiamusi University, Jiamusi City, Heilongjiang Province 154007, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, \rJiamusi University, Jiamusi City, Heilongjiang Province 154007, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, \rJiamusi University, Jiamusi City, Heilongjiang Province 154007, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Dong","family":"Meng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, \rJiamusi University, Jiamusi City, Heilongjiang Province 154007, China."},{"name":"Xuzhou Xingchen Women and Children\u2019s Hospital, Xuzhou","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Qi","family":"Niu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, \rJiamusi University, Jiamusi City, Heilongjiang Province 154007, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Run","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, \rJiamusi University, Jiamusi City, Heilongjiang Province 154007, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, \rJiamusi University, Jiamusi City, Heilongjiang Province 154007, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Xuan","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, \rJiamusi University, Jiamusi City, Heilongjiang Province 154007, 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