{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:59:05Z","timestamp":1787320745236,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Prodrug nanoassemblies formed by the self\u2010assembly of prodrugs represent an emerging platform, offering advantages such as high drug loading, facile preparation, and tumor selectivity. However, existing prodrug nanoassemblies primarily depend on noncovalent intermolecular interactions to maintain structural integrity, rendering them vulnerable to in vivo instability and severely constraining their clinical translation. To overcome those limitations, we introduce a mild and efficient thiol\u2010ene click reaction to construct prodrug nanoassemblies reinforced by a covalently crosslinked network. Specifically, prodrugs are designed by conjugating cabazitaxel (CTX) to tri\u2010alkene\u2010containing side chains via tumor redox\u2010responsive bonds. These prodrugs spontaneously assemble into nanoassemblies enriched with surface\u2010exposed olefin groups, which are subsequently \u201clocked\u201d by covalent crosslinking using tetra\u2010arm thiol crosslinkers. The resulting covalently crosslinked prodrug nanoassemblies exhibit markedly improved stability, leading to prolonged systemic circulation and enhanced tumor accumulation, thereby translating into superior antitumor efficacy. Moreover, the redox\u2010cleavable bond enables tumor microenvironment\u2010responsive drug release, effectively mitigating the systemic toxicity of CTX while preserving its antitumor potency. Collectively, this covalent \u201clocking\u201d strategy provides a notable advancement in optimizing the structural stability of prodrug nanoassemblies and offers a promising strategy for developing novel chemotherapeutic delivery platforms that integrate circulatory stability with tumor selectivity.<\/jats:p>","DOI":"10.1002\/adhm.71453","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:02:43Z","timestamp":1784628163000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Covalent \u201cLocking\u201d of Prodrug Nanoassemblies via Thiol\u2010Ene Click Crosslinking for Potent Antitumor Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Xuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Wuya College of Innovation Shenyang Pharmaceutical University  Shenyang 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