{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T07:10:08Z","timestamp":1788765008543,"version":"build-2803163510"},"reference-count":82,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":248,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2021-03835"],"award-info":[{"award-number":["RGPIN-2021-03835"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Biomaterials"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Cancer therapies are often limited by poor cellular specificity and tumor microenvironment\u2010mediated immunosuppression. We developed a dual\u2010function graphene oxide (GO)\u2013based gene delivery platform combining direct cancer cell elimination with stromal and immune reprogramming. CD47\u2010targeting siRNA and ANT1\u2010encoding plasmid DNA selectively induced apoptosis in tumor cells, while TGF\u03b2\u2010targeting siRNA altered cancer\u2010associated fibroblasts (CAFs) phenotype and was associated with a shift in macrophage polarization toward a pro\u2010inflammatory, tumor\u2010restraining phenotype. We evaluated this approach in a 3D multicellular lung cancer model consisting of A549\u2009cells, human lung fibroblasts, and THP1\u2010derived macrophages. TGF\u03b2 silencing alone modulated stromal and immune features without direct cytotoxicity, whereas CD47\/ANT1 modulation reduced overall cell viability to \u223c51%. When both therapeutic functions were applied together, overall cell viability was further reduced to \u223c29%. EGFR\u2010targeted GO\u2010CD47\u2010ANT1 (GE11\u2010peptide modified formulation) enhanced tumor\u2010cell uptake and selective apoptosis in CK7\n                    <jats:sup>+<\/jats:sup>\n                    cancer cells to 91%, while sparing CK7\n                    <jats:sup>\u2212<\/jats:sup>\n                    nonmalignant populations (16%). Mechanistically, combined therapy suppressed immunosuppressive macrophage markers (CD163, IL10, TGF\u03b2), restored epithelial integrity (E\u2010cadherin 3.5\u2010fold), and attenuated CAF activation (\u03b1SMA 0.3\u2010fold; vimentin 0.6\u2010fold). GE11 peptide functionalization shifted nanocarrier internalization toward EGFR\u2010mediated cancer cell uptake, minimizing off\u2010target delivery to fibroblasts and macrophages. These findings demonstrate that synergistic modulation of cancer cells and the tumor microenvironment is essential for robust and selective tumor elimination. Our study establishes a modular, mechanism\u2010informed GO platform integrating dual therapeutic functions\u2014targeted cancer cell killing and microenvironmental reprogramming\u2014highlighting its translational potential in physiologically relevant tumor models.\n                  <\/jats:p>","DOI":"10.1155\/ijbm\/3462859","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:58:06Z","timestamp":1788764286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Graphene Oxide\u2013Based Multigene Delivery for Cancer Elimination via Stromal and Immune Reprogramming"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9579-5704","authenticated-orcid":false,"given":"Francesca","family":"Grilli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3864-7999","authenticated-orcid":false,"given":"Sadman","family":"Sakib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5519-6915","authenticated-orcid":false,"given":"Fabio","family":"Variola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-6821","authenticated-orcid":false,"given":"Shan","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5738"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/clinpract11030056"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes16050569"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2021.04.002"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197111"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2019.105036"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s11671-020-3281-7"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202006918"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.02.030"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202400431"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.01.030"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1063\/5.0115464"},{"key":"e_1_2_12_13_2","doi-asserted-by":"crossref","unstructured":"GrantG.andFerrerC. 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