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This review examines recent advances in targeted immune modulation through smart biomaterials, programmable biopharmaceuticals, and hybrid biomaterial\u2013biologic systems. A structured literature review was conducted using peer-reviewed studies published between 2022 and 2026 from major biomedical databases. The reviewed evidence indicates that smart biomaterials can respond to disease-associated microenvironmental signals, such as pH changes, hypoxia, oxidative stress, and inflammatory enzymes, enabling localized and context-dependent therapeutic activity. Programmable biopharmaceuticals further enhance precision by directing immune-cell behavior and molecular signaling through engineered biological mechanisms. In addition, hybrid biomaterial\u2013biologic platforms combine environmental responsiveness with the potency of biologic therapeutics, improving immune targeting and reducing unintended systemic effects. Collectively, these technologies support a transition from conventional systemic immunomodulation toward adaptive and site-specific immune control. Despite significant progress, important challenges remain, including biological complexity, manufacturing scalability, long-term safety assessment, and regulatory translation. Nevertheless, the convergence of biomaterials science, synthetic biology, and immunoengineering is creating new opportunities for precision immunotherapy. Targeted immune modulation through programmable and responsive therapeutic systems represents a promising framework for developing safer, more effective, and clinically durable next-generation immunomodulatory therapies.<\/jats:p>","DOI":"10.1177\/08853282261483961","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:58:20Z","timestamp":1792180700000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted immune modulation through smart biomaterials and programmable biopharmaceuticals: A review"],"prefix":"10.1177","author":[{"given":"Hosein","family":"Yousefi","sequence":"first","affiliation":[{"name":"CT.C, Islamic Azad University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3948-4642","authenticated-orcid":false,"given":"Cobra","family":"Moradian","sequence":"additional","affiliation":[{"name":"CT.C, Islamic Azad University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00554-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2023.0304"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.04.013"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179256"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.910022"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-022-00016-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-024-03005-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1201\/9781003300311"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0101"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrp.2022.101041"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-69017-8"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering12111178"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1063\/5.0238817"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2025.125972"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123713"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202409422"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202209778"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.4c00537"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202411889"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13770-022-00491-z"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1669399"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202403786"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202514484"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbac009"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.5c01425"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13770-021-00419-z"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123568"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03695-2"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.114372"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bsheal.2022.11.002"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-024-02758-0"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202505413"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.37349\/etat.2022.00093"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.5c01385"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1039\/D3BM01213A"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.3390\/polym14030476"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1039\/D3NR05768B"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1320807"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1165576"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.6c00123"},{"key":"e_1_3_3_42_2","first-page":"1","article-title":"Engineering multi-specific nano-antibodies for cancer immunotherapy","volume":"26","author":"Fan YN","year":"2025","unstructured":"Fan YN, Zhu L, Qing YX, et al. 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