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While membrane fusion carriers bypass endosomal entrapment, their lack of cell specificity induces non\u2010target cytotoxicity. To overcome these limitations, we developed a stiffness\u2010gated mRNA delivery platform (PGC@FM). This system features a PLGA core loaded with G0\u2010C14 dendrimer\/mRNA complexes and coated with an engineered, low\u2010stiffness tumor cell fusion membrane (FM). The membrane stiffness is strategically reduced via unsaturated fatty acid enrichment, enabling direct cytoplasmic delivery through selective fusion with low\u2010stiffness target cells. Conversely, encountering high\u2010stiffness non\u2010target cells, PGC@FM undergoes endocytosis and lysosomal degradation, minimizing off\u2010target effects. 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These research results indicate that by leveraging the biophysical principle of membrane rigidity compatibility, highly selective mRNA delivery can be achieved, providing new ideas for the development of mRNA delivery carriers.<\/jats:p>","DOI":"10.1002\/adma.202518208","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T06:11:28Z","timestamp":1768630288000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Stiffness\u2010Gated Cytoplasmic mRNA Delivery Through Engineered Membrane Fusion for Breast Cancer Immunotherapy"],"prefix":"10.1002","volume":"38","author":[{"given":"Zhaoxu","family":"Chen","sequence":"first","affiliation":[{"name":"Lab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular &amp; Neuroimaging, Ministry of Education School of Life Science and Technology Xidian University Xi'an Shaanxi P. R. 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