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In this study, we produced near\u2010infrared (NIR)\u2010induced multi\u2010shell upconversion nanoparticle (MUN)\u2010based therapeutic nanocarriers co\u2010loaded with chlorin e6 (Ce6) and indoximod (IND) (FMUN3\u2010Ce6\/IND) to combine tumor\u2010targeted photodynamic therapy (PDT) with immunotherapy. Upconversion nanoparticles doped with rare\u2010earth elements are synthesized into multi\u2010shell structures to improve their upconversion luminescence efficiency. In particular, their emission intensity in the red region, which is the excitation wavelength of Ce6, increased by \u223c519 times compared with the core nanoparticles, which enhanced the PDT effect. The MUN\u2010based nanocarriers showed more than 18\u2010fold better ROS generation than free Ce6 under 808\u00a0nm NIR laser irradiation. FMUN3\u2010Ce6\/IND nanocarriers conjugated with a folic acid ligand showed particularly high phototoxicity to HeLa cells overexpressing folate receptors due to their active targeting effect. FMUN3\u2010Ce6\/IND nanocarriers increased the ratio of CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    to CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    T cells by approximately 5.4\u2010fold compared to FMUN3\u2010Ce6 without IND, indicating that inhibition of Trp metabolism by IND effectively promotes CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell proliferation and suppresses Treg cells, thereby enhancing the antitumor immune response. Furthermore, the synergistic antitumor efficacy of FMUN3\u2010Ce6\/IND combining PDT and immunotherapy under in vivo conditions is demonstrated. These results suggest that multi\u2010shell FMUN\u2010based nanocarriers offer a promising platform for synergistic combination therapy, addressing the limitations of monotherapy with IDO inhibitors and overcoming the restricted tissue penetration and low ROS generation associated with conventional PDT.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202504598","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T06:26:51Z","timestamp":1768631211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhanced Upconversion Luminescent Nanocarrier for Effective Tumor\u2010Targeted Photodynamic Therapy Combined with Immunotherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Jongseon","family":"Choi","sequence":"first","affiliation":[{"name":"Graduate School of Energy Science and Technology Chungnam National University  Daejeon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyoung Soo","family":"Yuh","sequence":"additional","affiliation":[{"name":"AngioLab, Inc.  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