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We report a biomimetic nanoplatform (PLL\/TNA\n                    <jats:sub>AKT2<\/jats:sub>\n                    @CM NPs) integrating biostable threose nucleic acid (TNA) with a donor\u2010derived cell membranes (CMs) \u201ccloak\u201d for subtype\u2010specific therapy. By complexing TNA\n                    <jats:sub>AKT2<\/jats:sub>\n                    antisense oligonucleotides with poly\u2010L\u2010lysine (PLL) and coating them with TNBS\u2010subtype membranes (MDA\u2010MB\u2010468 or MDA\u2010MB\u2010231), we achieve potent homotypic affinity. PLL\/TNA\n                    <jats:sub>AKT2<\/jats:sub>\n                    @468CM NPs exhibited significant\u00a0enhanced uptake in donor\u2010matched basal\u2010like 1 cells compared to heterotypic TNBC, non\u2010TNBC and normal epithelial cells. Mechanistically, these nanoparticles internalize via a rapid\u00a0membrane\u2010fusion, bypassing endosomal entrapment for direct cytosolic delivery. This facilitates robust silencing of the AKT2 oncogene, achieving a\u00a0\n                    <jats:bold>\u223c<\/jats:bold>\n                    70% protein knockdown and outperforming conventional transfection reagents. In a drug\u2010resistant MDA\u2010MB\u2010468 xenografts, systemic administration led to superior tumor accumulation, effective AKT2 knockdown, and significant tumor regression via the p21\/Caspase\u20103 apoptotic axis, without systemic toxicity. This versatile \u201cplug\u2010and\u2010play\u201d strategy addresses tumor heterogeneity and endosomal sequestration, providing a transformative paradigm for targeted nucleic acid delivery in refractory cancers.\n                  <\/jats:p>","DOI":"10.1002\/advs.76100","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T19:05:43Z","timestamp":1781291143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Membrane Fusion\u2010Mediated Cytosolic Delivery of Threose Nucleic Acids via Homotypic Nanoparticles Overcomes Drug Resistance in Triple\u2010Negative Breast Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Wei","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Chemistry and State Key Laboratory of Marine Environmental Health  Kowloon Tong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan Juin 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