{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:00:30Z","timestamp":1790103630056,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP2008698"],"award-info":[{"award-number":["APP2008698"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Particle\u2010based artificial antigen\u2010presenting cells (aAPCs) are widely used for ex vivo T cell activation, but rigid, high\u2010avidity stimulation can promote differentiation and exhaustion, reducing therapeutic efficacy. Because T cells sense mechanical forces through the T cell receptor, we engineered nanocapsule aAPCs with three stiffness regimes, spanning MPa to GPa Young's moduli, and two \u03b1CD3\/\u03b1CD28 ligand densities to define how mechanical and biochemical cues shape primary human T cell responses. Across six formulations benchmarked against Dynabeads, stiffness and ligand density acted as orthogonal but synergistic design parameters. Expansion increased with both variables, and the stiff, high\u2010density nanocapsules matched or exceeded Dynabead\u2010mediated expansion by day 8. However, unlike Dynabeads, enhanced expansion did not coincide with strong exhaustion or terminal differentiation. Nanocapsules maintained CD8\n                    <jats:sup>+<\/jats:sup>\n                    PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    frequencies near baseline, mitigated Dynabead\u2010associated CD4\n                    <jats:sup>+<\/jats:sup>\n                    bias, and promoted CD8 enrichment, with CD8\/CD4 ratios reaching approximately 2.7. They also produced transient, tunable CD25 upregulation, reduced granzyme B expression, and preserved TCF\u20101\n                    <jats:sup>+<\/jats:sup>\n                    stem\u2010like populations depending on signal strength. These results establish mechano\u2010chemically tunable nanocapsule aAPCs as a versatile platform for generating expanded, CD8\u2010enriched T cell products with reduced exhaustion\u2010associated phenotypes for adoptive cell therapy manufacturing and provide a rational framework for programmable T cell product design ex vivo applications.\n                  <\/jats:p>","DOI":"10.1002\/smll.75859","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:05:26Z","timestamp":1790100326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechano\u2010Chemical Coordination of Nanoparticle\u2010Based Artificial Antigen\u2010Presenting Cells Synergistically Tunes T Cell Activation and Expansion Phenotypes"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8150-2461","authenticated-orcid":false,"given":"Zichao","family":"Guo","sequence":"first","affiliation":[{"name":"School of Chemical Engineering College of Engineering and Information Technology Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4043-6696","authenticated-orcid":false,"given":"Fei","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering College of Engineering and Information Technology Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering College of Engineering and Information Technology Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilin","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering College of Engineering and Information Technology Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8932-6135","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering College of Engineering and Information Technology Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7275-853X","authenticated-orcid":false,"given":"Supun","family":"Ranaweera","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering College of Engineering and Information Technology Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hui","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering College of Engineering and Information Technology Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3365-3759","authenticated-orcid":false,"given":"Chun\u2010Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering College of Engineering and Information Technology Adelaide University  Adelaide South Australia 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