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The spatiotemporal fate of vaccine components within the body is key to overcoming this hurdle. Here, we report a cascade \u201cLymph nodes\u2013Antigen presenting cells\u2013Endoplasmic reticulum (LAE)\u201d delivery strategy enabled by engineering the surface topography of nanoparticles. We designed mesoporous silica nanoparticles with smooth, short\u2010spiked, and long\u2010spiked (SNL) morphologies. Among them, SNL showed superior antigen peptide delivery and APC activation. Mechanistically, SNL enhanced Piezo1\u2010mediated calcium influx through mechanical stimulation, promoting dendritic cell activation and increasing antigen trafficking to the endoplasmic reticulum (ER), a key site for cross\u2010presentation. Capitalizing on this ER\u2010targeting capability, we co\u2010loaded the STING agonist 2\u20323\u2032\u2010cGAMP with antigen peptides into SNL, yielding synergistic immune activation. This combination induced potent CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses, delayed tumor progression in lymphoma and cervical cancer models, and conferred cross\u2010protective immunity in a SARS\u2010CoV\u20102 vaccination model. Our study establishes nanoparticle morphology as an important design parameter for orchestrating the precise intracellular delivery of vaccine components, offering a generalizable platform for next\u2010generation vaccines.\n                  <\/jats:p>","DOI":"10.1002\/adma.73396","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T18:56:23Z","timestamp":1779562583000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Morphology\u2010Driven Cascade Delivery of Antigens for Potent T Cell Immunity"],"prefix":"10.1002","volume":"38","author":[{"given":"Shuting","family":"Bai","sequence":"first","affiliation":[{"name":"Key Laboratory of Drug\u2010Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory For Plant\u2010Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University  Chengdu P. 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