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Cancer is often characterized by dysregulated copper metabolism, which plays a crucial role in modulating tumor cell properties like cell proliferation, angiogenesis and metastasis. Therefore, exploiting their metabolic vulnerability using copper overload-based anticancer strategies has emerged as a novel approach. Despite the significant therapeutic potential of copper, its application in anticancer therapy has been limited due to systemic toxicity and non-target localization. In the present study we report targeted delivery of copper to the tumor site and its anticancer therapeutic potential of copper conjugated aminated arabinogalactan (Cu-aAG) in HCC. The synthesized compound was characterized using FT-IR, NMR, Mass spectroscopy and assessed for its anti-cancer therapeutic potential against the Wistar rat model of\n                    <jats:italic>N-nitrosodiethylamine-<\/jats:italic>\n                    induced hepatocellular carcinoma. The chemical characterization of Cu-aAG revealed successful copper complexation as evidenced by characteristic FT-IR peaks and elemental analysis showing 1.19% copper content. The involvement of amine and hydroxyl groups in the complexation was further confirmed by NMR and mass spectral analysis thus ensuring formation of stable, copper-centered co-ordination complexes. Cu-aAG treatment to tumor bearing Wistar rats significantly decreased tumor burden and tumor multiplicity (3.92\u2009\u00b1\u20092.9) as compared to untreated Tumor group (18.90\u2009\u00b1\u20093.02). Further, Cu-aAG treatment induced apoptotic cell death, cell cycle arrest, and inhibited angiogenesis. These findings highlight the potential of targeted delivery of copper overload-mediated anticancer therapy for inhibiting tumor growth and progression in HCC.\n                  <\/jats:p>","DOI":"10.1007\/s10534-025-00772-9","type":"journal-article","created":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T18:31:53Z","timestamp":1763922713000},"page":"631-650","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Asialoglycoprotein receptor-mediated delivery of copper to hepatic tumors exerted inhibitory effect on tumor growth and progression"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8548-4363","authenticated-orcid":false,"given":"Maya P.","family":"Shetty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6278-4627","authenticated-orcid":false,"given":"Priti","family":"Sule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3004-2266","authenticated-orcid":false,"given":"Suresh D.","family":"Kulkarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4156-6292","authenticated-orcid":false,"given":"Pradip","family":"Chaudhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3697-2632","authenticated-orcid":false,"given":"Sanjay","family":"Bharati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,23]]},"reference":[{"key":"772_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114897","author":"S Abdolmaleki","year":"2023","unstructured":"Abdolmaleki S, Panjehpour A, Khaksar S, Ghadermazi M, Rostamnia S (2023) Evaluation of central-metal effect on anticancer activity and mechanism of action of isostructural Cu(II) and Ni(II) complexes containing pyridine-2,6-dicarboxylate. 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