{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:59:36Z","timestamp":1790884776563,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"55","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0210800"],"award-info":[{"award-number":["2020YFA0210800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62575068"],"award-info":[{"award-number":["62575068"]}],"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":["62175031"],"award-info":[{"award-number":["62175031"]}],"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":["22274023"],"award-info":[{"award-number":["22274023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Photodynamic therapy (PDT)\u2010induced immunogenic cell death (ICD) is an important approach for enhancing in situ tumor immunogenicity and activating systemic immune response. However, the tumor immunosuppressive microenvironment often limits the immunotherapeutic effect of single\u2010modal PDT. Notably, the adenosine\u2010A2A receptors (A2AR)\u2010related signal pathway plays a key role in tumor immunosuppression. Herein, we report a multifunctional nanoplatform (SPN\n                    <jats:sub>S<\/jats:sub>\n                    ) for the targeted delivery of mimetic enzyme (Hemin), photosensitizers (PCPDTBT) and A2AR inhibitor (SCH58261) cancer cells. This platform aims to overcome tumor hypoxia and adenosine\u2010mediated immunosuppression, thereby further improving the PDT\u2010immunotherapy efficacy. In vitro and in vivo results demonstrate that our SPN\n                    <jats:sub>S<\/jats:sub>\n                    can synergistically regulate tumor immunosuppression through a combination of oxygen supply (enhancing PDT efficacy and alleviating A2AR\u2010mediated inhibition), ICD\u2010induced tumor immunogenicity (via PDT), and direct A2AR blockade (using an A2AR antagonist). After intravenous injection of SPN\n                    <jats:sub>S<\/jats:sub>\n                    and then phototherapy in vivo, the alleviated hypoxia microenvironment and adenosine\u2010mediated immunosuppression can lead to amplifying ICD\u2010induced immune responses. This is accompanied by enhanced DC maturation, increased tumor infiltration of immune effector cells and elevated secretion of antitumor cytokines. This work highlights that the synergistic regulation of tumor immunosuppression is an effective therapeutic strategy to inhibit tumor growth and suppress metastasis.\n                  <\/jats:p>","DOI":"10.1002\/smll.74971","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T08:53:26Z","timestamp":1785747206000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Overcoming Tumor Hypoxia and Adenosine\u2010mediated Immunosuppression for Boosting Photodynamic Therapy and Systemic Antitumor Immune Responses"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-1461","authenticated-orcid":false,"given":"Xiaolong","family":"Zhang","sequence":"first","affiliation":[{"name":"The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University  Fuzhou P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3591-3224","authenticated-orcid":false,"given":"Lei","family":"Ding","sequence":"additional","affiliation":[{"name":"The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University  Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyue","family":"Wang","sequence":"additional","affiliation":[{"name":"The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University  Fuzhou P. R. China"},{"name":"College of Life Science Fujian Agriculture and Forestry University  Fuzhou Fujian P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyi","family":"Liang","sequence":"additional","affiliation":[{"name":"The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University  Fuzhou P. R. China"},{"name":"College of Life Science Fujian Agriculture and Forestry University  Fuzhou Fujian P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsheng","family":"Li","sequence":"additional","affiliation":[{"name":"The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University  Fuzhou P. R. 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