{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:07:13Z","timestamp":1793830033459,"version":"4.6.1"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T00:00:00Z","timestamp":1739059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204322"],"award-info":[{"award-number":["82204322"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373821"],"award-info":[{"award-number":["82373821"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["20240484502"],"award-info":[{"award-number":["20240484502"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Exploration"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The insufficient infiltration and functional inhibition of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells due to tumor microenvironment (TME) are considered enormous obstacles to anti\u2010tumor immunotherapy. Herein, a pH\u2010responsive core\u2010shell manganese phosphate nanomodulator co\u2010loading siPD\u2010L1 and Mn\n                    <jats:sup>2+<\/jats:sup>\n                    into nanoparticles coated with hyaluronic acid was prepared, which was aimed at the bidirectional reprogramming the tumor microenvironment: (1) \u201cBrakes off,\u201d restoring CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells function by siPD\u2010L1 knockdowning PD\u2010L1 expression of tumor cells; (2) \u201cStep on the accelerator,\u201d promoting CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells infiltration in tumors tissue based on the multidimensional immune effects of Mn\n                    <jats:sup>2+<\/jats:sup>\n                    (immunogenic cell death induced the enhancing cGAS\u2010STING pathway, the proliferation and maturation of relative immune cells). Additionally, this strategy could induce macrophage polarization and inhibit the regulatory T cells in tumor site. This work provided a manganese phosphate nanomodulator to reprogram the immune TME for an enhanced comprehensive anti\u2010tumor effect of triple negative breast cancer, which offers a robust method for tumor immunotherapy in future clinical applications.\n                  <\/jats:p>","DOI":"10.1002\/exp.70009","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T20:25:13Z","timestamp":1739219113000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a \u201cBrakes Off\/ Step on the Accelerator\u201d Core\u2010Shell Manganese Phosphate\/siPD\u2010L1 Modulator"],"prefix":"10.1002","volume":"5","author":[{"given":"Fei","family":"Xia","sequence":"first","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao\u2010di Herbs, Artemisinin Research Center, and 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