{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:50:48Z","timestamp":1792065048436,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Peptide Science"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glypican\u20103 (GPC\u20103) is a cell\u2010surface glycoprotein, highly expressed in hepatocellular carcinoma (HCC) but largely absent in normal adult liver tissues, making it a clinically compelling biomarker and therapeutic target. Although monoclonal antibodies and antibody\u2010drug conjugates have proven to be GPC\u20103\u2010targeted therapies, their large molecular size, slow pharmacokinetics, and potential immunogenicity limit their diagnostic applications. Peptide ligands offer an attractive alternative owing to their low molecular weight, rapid tumor penetration, favorable clearance profiles, synthetic accessibility, and ease of chemical modification. This topical review highlights the development of linear and cyclic GPC\u20103\u2010binding peptides over the past two decades, developed primarily via phage display, rational optimization, and structure\u2010guided approaches, enabling PET, SPECT, and fluorescence imaging of HCC in preclinical models. Recent refinements, including albumin\u2010binding modifications and cyclization strategies, have improved tumor\u2010to\u2010liver contrast and in\u00a0vivo stability. This review summarizes the biological significance of GPC\u20103, compares peptides and peptide probes as targeting modalities, and critically analyzes recent advances in linear and cyclic peptide\u2010based GPC\u20103 imaging probes. We also emphasized the importance, current challenges, and future opportunities in AI\/ML\u2010based design of peptide ligands for HCC theranostics.<\/jats:p>","DOI":"10.1002\/psc.70134","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:16:07Z","timestamp":1791173767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Antibodies: Glypican\u20103\u2010Targeting Peptides for Precision Hepatocellular Carcinoma Theranostics"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8399-7618","authenticated-orcid":false,"given":"Narendra Raju","family":"Nagpure","sequence":"first","affiliation":[{"name":"Biomimetic Peptide Engineering Laboratory, Department of Chemistry Indian Institute of Technology Ropar  Rupnagar Punjab 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