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However, its clinical effectiveness is often constrained by such factors as tumor heterogeneity, the abundance of M2 macrophages, tumor\u2010vascular hypoxia, and the immunosuppressive microenvironment created by immune checkpoint (IC) complexes. In this work, an effective photosensitizer (TSPA) with aggregation\u2010induced emission (AIE) nature is adopted to counter above limitations. The synthesized TSPA demonstrated potent efficacy in eradicating primary tumors because of their effective generation reactive oxygen species (ROS) after undergoing photodynamic therapy (PDT) process. Moreover, TSPA can improve hypoxic conditions in tumor by normalizing blood vessels, and can instigate immunogenic cell death\u00a0(ICD), thus stimulating immune cell activation. TSPA demonstrates the ability to reprogram M2 tumor\u2010associated macrophages (TAMs) into the anti\u2010tumor M1 phenotype, thereby increasing the infiltration of M1 macrophages within the tumor. This procedure notably ameliorates the immune microenvironment, effectively suppressing the long\u2010term metastasis of breast cancer (BC). This research notably enhances the efficiency of tumor immunotherapy and is anticipated to emerge as a new strategy for improving the tumor's immunosuppressive microenvironment and overcoming immune evasion.<\/jats:p>","DOI":"10.1002\/smll.202503355","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T03:52:36Z","timestamp":1747021956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transforming the Tumor Microenvironment: An Outstanding AIE\u2010Active Photosensitizer to Boost the Effectiveness of Immunotherapy"],"prefix":"10.1002","volume":"21","author":[{"given":"Muzhou","family":"Teng","sequence":"first","affiliation":[{"name":"Gansu Provincial Maternity and Child\u2010Care Hospital(Gansu Provincial Central Hospital)  Lanzhou 730050 China"},{"name":"The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Gu","sequence":"additional","affiliation":[{"name":"The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongxin","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihang","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Nanchang Hangkong University  Nanchang 330063 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yirong","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitao","family":"Fan","sequence":"additional","affiliation":[{"name":"The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4930-0958","authenticated-orcid":false,"given":"Qing","family":"Wan","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Nanchang Hangkong University  Nanchang 330063 China"},{"name":"AIE institute South China University of Technology  Guangzhou 510640 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumin","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Hospital &amp; Clinical Medical School Lanzhou University  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-023-00560-y"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.03.033"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.04.016"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28076-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202007603"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.026"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00778-2"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-326928"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.09.010"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c13732"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202109258"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202209799"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01132-2"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.05.004"},{"key":"e_1_2_7_15_1","volume":"13","author":"Sun Y.","year":"2021","journal-title":"Sci. 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