{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:45:38Z","timestamp":1792464338353,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001352","name":"National University of Singapore","doi-asserted-by":"publisher","award":["A\u20100009163\u201001\u201000"],"award-info":[{"award-number":["A\u20100009163\u201001\u201000"]}],"id":[{"id":"10.13039\/501100001352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"publisher","award":["H23J2a0097"],"award-info":[{"award-number":["H23J2a0097"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A major challenge to effective cancer gene therapy is the absence of delivery systems that both protect nucleic acids in circulation and release them efficiently inside tumor cells. Nucleic acids are rapidly degraded by nucleases, cleared from the blood, and poorly internalized due to size and charge. Existing vectors address parts of this problem but remain limited by cytotoxicity, instability, or inadequate tumor selectivity. Here, a lock\u2010and\u2010shield strategy integrating a hyaluronic acid Nanogel with a hybrid membrane shell\u00a0(Nanogel@hMVs) is reported. The Nanogel \u201clock\u201d physically entraps nucleic acids with high efficiency (81.6%\u201389.2%) and incorporates dual pH\/redox\u2010responsive linkers for controlled release under tumor\u2010associated conditions. The membrane \u201cshield\u201d, derived from tumor cell membranes and fusogenic lipids, reinforces systemic stability, preserves homotypic recognition, and mediates fusion\u2010driven cytosolic entry, ensuring tumor\u2010selective and efficient intracellular delivery. Nanogel@hMVs remain stable for 30 days, promote efficient uptake with minimal lysosomal sequestration, and silence Survivin. Across DNAzyme, siRNA, and ASO, they consistently produce potent gene silencing and in vitro antitumor activity. In vivo systemic administration yields preferential tumor accumulation, marked tumor inhibition, and prolonged survival without detectable toxicity. Collectively, Nanogel@hMVs establish a robust, safe, and adaptable lock\u2010and\u2010shield platform for systemic nucleic acid delivery in cancer therapy.<\/jats:p>","DOI":"10.1002\/adma.202518041","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T14:47:58Z","timestamp":1764946078000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lock\u2010and\u2010Shield Strategy Enables Stable and Stimuli\u2010Responsive Tumor\u2010Targeted Gene Delivery"],"prefix":"10.1002","volume":"38","author":[{"given":"Siqin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering National University of Singapore 4 Engineering Drive 4 Singapore 117585 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongzhi","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science Guizhou University 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