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Res."],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively used as carriers in targeted drug delivery and has several advantages in the field of magnetic hyperthermia, chemodynamic therapy and magnet assisted radionuclide therapy. The characteristics of SPIONs can be tailored to deliver drugs into tumor <jats:italic>via<\/jats:italic> \u201cpassive targeting\u201d and they can also be coated with tissue-specific agents to enhance tumor uptake <jats:italic>via<\/jats:italic> \u201cactive targeting\u201d. In our earlier studies, we developed HCC specific targeting agent- \u201cphosphorylated galactosylated chitosan\u201d(PGC) for targeting asialoglycoprotein receptors. Considering their encouraging results, in this study we developed a multifunctional targeting system- \u201cphosphorylated galactosylated chitosan-coated magnetic nanoparticles\u201d(PGCMNPs) for targeting HCC. PGCMNPs were synthesized by co-precipitation method and characterized by DLS, XRD, TEM, VSM, elemental analysis and FT-IR spectroscopy. PGCMNPs were evaluated for in vitro antioxidant properties, uptake in HepG2 cells, biodistribution, in vivo toxicity and were also evaluated for anticancer therapeutic potential against NDEA-induced HCC in mice model in terms of tumor status, electrical properties, antioxidant defense status and apoptosis. The characterization studies confirmed successful formation of PGCMNPs with superparamagnetic properties. The internalization studies demonstrated (99\u2013100)% uptake of PGCMNPs in HepG2 cells. These results were also supported by biodistribution studies in which increased iron content (296%) was noted inside the hepatocytes. Further, PGCMNPs exhibited no in vivo toxicity. The anticancer therapeutic potential was evident from observation that PGCMNPs treatment decreased tumor bearing animals (41.6%) and significantly (p\u2009\u2264\u20090.05) lowered tumor multiplicity. Overall, this study indicated that PGCMNPs with improved properties are efficiently taken-up by hepatoma cells and has therapeutic potential against HCC. Further, this agent can be tagged with <jats:sup>32<\/jats:sup>P and hence can offer multimodal cancer treatment options <jats:italic>via<\/jats:italic> radiation ablation as well as magnetic hyperthermia.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>\n          <jats:p>Schematic illustration of PGCMNPs synthesis, characterization and its anticancer potential: PGCMNPs were synthesized by co-precipitation method. The successful synthesis of PGCMNPs was confirmed by physical and chemical characterizations. PGCMNPs were biocompatible and exhibited no toxicity at tested parameters. PGCMNPs demonstrated higher uptake in HepG2 cells. The anticancer therapeutic potential of PGCMNPs in HCC mouse model, was evident from improved tumor statistics, increased low conductivity tumors and increased apoptosis mediated cell death.<\/jats:p>","DOI":"10.1007\/s13346-024-01655-1","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T15:44:44Z","timestamp":1720712684000},"page":"1023-1042","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Anticancer therapeutic potential of multimodal targeting agent- \u201cphosphorylated galactosylated chitosan coated magnetic nanoparticles\u201d against N-nitrosodiethylamine-induced hepatocellular carcinoma"],"prefix":"10.1007","volume":"15","author":[{"given":"Anushree","family":"Udupi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Shetty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesil Mathew","family":"Aranjani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Bharati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"issue":"4","key":"1655_CR1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41578-020-00269-6","volume":"6","author":"MT Manzari","year":"2021","unstructured":"Manzari MT, Shamay Y, Kiguchi H, Rosen N, Scaltriti M, Heller DA. 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All animal experiments were performed as per the guidelines of Committee for the Control and Supervision of experiments on animals (IAEC\/KMC\/85\/2017) (Manipal Academy of Higher Education, Manipal) and ARRIVE guidelines. Experiments were conducted under controlled conditions (temperature: 25\u00b12\u00b0C, humidity: 65-80%) with 12 hours of light and dark cycle. Animals were provided with ad libitum supply of clean drinking water and standard animal pellet diet (VRK nutritional solutions, Maharashtra, India). After the completion of respective period of treatments animals were euthanized using large dose of thiopental sodium (50 mg\/kg bw, intraperitoneal).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval statement"}},{"value":"The authors report that there are no competing interests to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}