{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:15:06Z","timestamp":1783674906069,"version":"3.55.0"},"reference-count":76,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Aberrant protein glycosylation contributes significantly to hepatocellular carcinoma (HCC) progression.\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u20101,4\u2010Galactosyltransferase 3 (B4GALT3), an enzyme involved in glycosylation, is overexpressed in HCC and promotes tumour growth by stabilizing integrin\n                      <jats:italic>\u03b2<\/jats:italic>\n                      1 (ITGB1). This study aimed to evaluate B4GALT3 as a therapeutic target and develop a precision nanotherapeutic approach for HCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Bioinformatics analyses using TCGA\u2010LIHC datasets identified B4GALT3 as a prognostic biomarker in HCC. Functional assays assessed the role of B4GALT3 in proliferation, migration, invasion and ITGB1 glycosylation in HCC cells. Subsequently, enzyme\u2010responsive 612\u2010AYR nanoparticles were engineered to deliver a specific B4GALT3 inhibitor selectively to tumour sites. The nanoparticles' biocompatibility, tumour\u2010targeting capability, retention and therapeutic efficacy were evaluated in both subcutaneous and orthotopic HCC mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>B4GALT3 enhanced HCC cell proliferation, migration, and invasion by increasing ITGB1 glycosylation, stabilizing its protein level and activating downstream signalling and cell\u2010cycle pathways. The 612\u2010AYR nanoparticles demonstrated excellent biocompatibility, tumour\u2010specific accumulation and prolonged retention in vivo. Treatment with these nanoparticles markedly suppressed tumour growth and metastasis in both mouse models through effective disruption of the B4GALT3\u2013ITGB1 signalling axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Targeting aberrant glycosylation via enzyme\u2010responsive 612\u2010AYR nanoparticles delivering a B4GALT3 inhibitor presents a promising precision therapeutic approach for HCC. This integrated strategy combining glycosylation\u2010targeted molecular biology and advanced nanotechnology offers a novel paradigm for personalized cancer treatment, holding significant therapeutic and diagnostic potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70415","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:32:20Z","timestamp":1779251540000},"page":"4989-5017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enzyme\u2010responsive 612\u2010AYR nanoparticles for targeted inhibition of B4GALT3\u2010mediated ITGB1 glycosylation in hepatocellular carcinoma"],"prefix":"10.1111","volume":"183","author":[{"given":"Xiaohui","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pathology The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University\/Hunan Cancer Hospital  Changsha 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