{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:18:25Z","timestamp":1787235505028,"version":"build-2736575974"},"reference-count":106,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T00:00:00Z","timestamp":1588204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Chitosan nanoparticles are well-known delivery systems widely used as polymeric carriers in the field of nanomedicine. Chitosan is a carbohydrate of natural origin: it is a biodegradable, biocompatible, mucoadhesive, polycationic polymer and it is endowed with penetration enhancer properties. Furthermore, it can be easily derivatized. Hepatocellular carcinoma (HCC) represents a remarkable health problem because current therapies, that include surgery, liver transplantation, trans-arterial embolization, chemoembolization and chemotherapy, present significant limitations due to the high risk of recurrence, to a lack of drug selectivity and to other serious side effects. Therefore, there is the need for new therapeutic strategies and for improving the liver-targeting to HCC. Nanomedicine consists in the use of nanoscale carriers as delivery systems to target and deliver drugs and\/or diagnostic agents to specific organs or tissues. Chitosan and its derivatives can be successfully used in the preparation of nanoparticles that, for their peculiar surface-properties, can specifically interact with liver tumor, by passive and active targeting. This review concerns the use of chitosan nanoparticles for the therapy and theranostics of HCC and liver-targeting.<\/jats:p>","DOI":"10.3390\/nano10050870","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T03:29:39Z","timestamp":1588562979000},"page":"870","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1194-9372","authenticated-orcid":false,"given":"Maria Cristina","family":"Bonferoni","sequence":"first","affiliation":[{"name":"Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0499-9419","authenticated-orcid":false,"given":"Elisabetta","family":"Gavini","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6268-8179","authenticated-orcid":false,"given":"Giovanna","family":"Rassu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5693-9151","authenticated-orcid":false,"given":"Marcello","family":"Maestri","sequence":"additional","affiliation":[{"name":"IRCCS Policlinico San Matteo Foundation, General Surgery, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2471-1355","authenticated-orcid":false,"given":"Paolo","family":"Giunchedi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.3892\/ijo.2013.1829","article-title":"Human hepatocyte carcinogenesis (review)","volume":"42","author":"Shiraha","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1053\/j.gastro.2007.04.061","article-title":"Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis","volume":"132","author":"Rudolph","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.ejso.2017.04.016","article-title":"Long-term follow-up after near-infrared fluorescence-guided resection of colorectal liver metastases: A retrospective multicenter analysis","volume":"43","author":"Handgraaf","year":"2017","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.biotechadv.2016.04.001","article-title":"Indocyanine green delivery systems for tumour detection and treatments","volume":"34","author":"Porcu","year":"2016","journal-title":"Biotechnol. Adv."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1111\/hpb.12057","article-title":"Combined use of intraoperative ultrasound and indocyanine green fluorescence imaging to detect liver metastases from colorectal cancer","volume":"15","author":"Peloso","year":"2013","journal-title":"HPB"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"474","DOI":"10.2174\/156720181205151104142906","article-title":"Opinion paper: Selective targeting of liver nodules. Present situation and new challenges to enhance indocyanine green captation from colorectal liver metastases","volume":"12","author":"Giunchedi","year":"2015","journal-title":"Curr. Drug Deliv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1517\/17425247.2015.1042452","article-title":"Development of thermosensitive chitosan\/glicerophospate injectable in situ gelling solutions for potential application in intraoperative fluorescence imaging and local therapy of hepatocellular carcinoma: A preliminary study","volume":"12","author":"Salis","year":"2015","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.3748\/wjg.v22.i12.3325","article-title":"Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: A review","volume":"22","author":"Xu","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrgastro.2016.193","article-title":"Liver transplantation for hepatocellular carcinoma: Outcomes and novel surgical approaches","volume":"14","author":"Sapisochin","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.jhep.2019.11.017","article-title":"Advances in resection and transplantation for hepatocellular carcinoma","volume":"72","author":"Vibert","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.4254\/wjh.v7.i26.2648","article-title":"Hepatocellular carcinoma: A comprehensive review","volume":"7","author":"Waller","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1053\/jhep.2002.32089","article-title":"Prognostic prediction and treatment strategy in hepatocellular carcinoma","volume":"35","author":"Bruix","year":"2002","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1517\/17425247.2013.770733","article-title":"Transarterial chemoembolization of hepatocellular carcinoma. Agents and drugs: An overview. Part 1","volume":"10","author":"Giunchedi","year":"2013","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1517\/17425247.2013.796359","article-title":"Transarterial chemoembolization of hepatocellular carcinoma\u2014Agents and drugs: An overview. Part 2","volume":"10","author":"Giunchedi","year":"2013","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.ejim.2014.03.001","article-title":"Multimodal treatment of hepatocellular carcinoma","volume":"25","author":"Graf","year":"2014","journal-title":"Eur. J. Intern. Med."},{"key":"ref_16","first-page":"797","article-title":"Systemic treatment of hepatocellular carcinoma: Past, present and future","volume":"9","author":"Cidon","year":"2017","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ejpb.2017.04.010","article-title":"Engineered polymeric microspheres obtained by multi-step method as potential systems for transarterial embolization and intraoperative imaging of HCC: Preliminary evaluation","volume":"117","author":"Porcu","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1080\/17425247.2017.1295036","article-title":"In situ forming biodegradable poly(\u03b5-caprolactone) microsphere systems: A challenge for transarterial embolization therapy. In vitro and preliminary ex vivo studies","volume":"14","author":"Salis","year":"2017","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1208\/s12249-014-0107-x","article-title":"Nanocarrier for poorly water-soluble anticancer drugs\u2014Barriers of translation and solutions","volume":"15","author":"Narvekar","year":"2014","journal-title":"AAPS PharmSciTech."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40824-019-0166-x","article-title":"Therapeutic efficacy of nanoparticles and routes of administration","volume":"23","author":"Chenthamara","year":"2019","journal-title":"Biomater. Res."},{"key":"ref_21","unstructured":"Elnaggar, M.H., Abushouk, A.I., Hassan, A.H.E., Lamloum, H.M., Benmelouka, A., Moatamed, S.A., Abd-Elmegeed, H., Attia, S., Samir, A., and Amr, N. (2019). Nanomedicine as a putative approach for active targeting of hepatocellular carcinoma. Semin. Cancer Biol., S1044-579X(19)30225-1."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.colsurfb.2019.02.036","article-title":"Poly (ethyl 2-cyanoacrylate) nanoparticles (PECA-NPs) as possible agents in tumor treatment","volume":"177","author":"Obinu","year":"2019","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Obinu, A., Gavini, E., Rassu, G., Riva, F., Calligaro, A., Bonferoni, M.C., Maestri, M., and Giunchedi, P. (2020). Indocyanine green loaded polymeric nanoparticles: Physicochemical characterization and interaction studies with Caco-2 cell line by light and transmission electron microscopy. Nanomaterials, 10.","DOI":"10.3390\/nano10010133"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nelemans, L.C., and Gurevich, L. (2020). Drug delivery with polymeric nanocarriers-cellular uptake mechanisms. Materials, 13.","DOI":"10.3390\/ma13020366"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8893","DOI":"10.1021\/acsnano.8b04315","article-title":"Oral Nanoparticles Exhibit Specific High-Efficiency Intestinal Uptake and Lymphatic Transport","volume":"12","author":"Kim","year":"2018","journal-title":"ACS Nano"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1080\/17425247.2018.1446937","article-title":"Lymph node metastases: Importance of detection and treatment strategies","volume":"15","author":"Obinu","year":"2018","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1080\/17425247.2018.1537260","article-title":"Nanoparticles in detection and treatment of lymph node metastases: An update from the point of view of administration routes","volume":"15","author":"Obinu","year":"2018","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s13205-019-1940-0","article-title":"Nanotechnology based therapeutic application in cancer diagnosis and therapy","volume":"9","author":"Singh","year":"2019","journal-title":"3 Biotech"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ahlawat, J., Henriquez, G., and Narayan, M. (2018). Enhancing the delivery of chemotherapeutics: Role of biodegradable polymeric nanoparticles. Molecules, 23.","DOI":"10.3390\/molecules23092157"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"494","DOI":"10.2174\/156720181304160521004609","article-title":"Biodegradable polymeric nanoparticles as the delivery carrier for drug","volume":"13","author":"Zhao","year":"2016","journal-title":"Curr. Drug Deliv."},{"key":"ref_31","unstructured":"Raj, S., Khurana, S., Choudhari, R., Kesari, K.K., Kamal, M.A., Garg, N., Ruokolainen, J., Das, B.C., and Kumar, D. (2019). Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy. Semin. Cancer Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15343","DOI":"10.1021\/acs.langmuir.8b02946","article-title":"Distinction between active and passive targeting of nanoparticles dictate their overall therapeutic efficacy","volume":"34","author":"Clemons","year":"2018","journal-title":"Langmuir"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.addr.2010.03.011","article-title":"Tumor delivery of macromolecular drugs based on the EPR effect","volume":"63","author":"Torchilin","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.colsurfb.2005.06.001","article-title":"Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery","volume":"44","author":"Gan","year":"2005","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.3390\/md13041819","article-title":"Stability of chitosan-a challenge for pharmaceutical and biomedical applications","volume":"13","author":"Winnicka","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.3390\/md13031133","article-title":"Chitin and chitosan preparation from marine sources. Structure, properties and applications","volume":"13","author":"Younes","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1016\/S0169-409X(01)00180-6","article-title":"Chitosan and its derivatives as intestinal absorption enhancers","volume":"50","author":"Thanou","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.2174\/0929867325666180927100817","article-title":"Chitosan-based polymer matrix for pharmaceutical excipients and drug delivery","volume":"26","author":"Khan","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.ijbiomac.2019.02.060","article-title":"Chitosan nanopolymers: An overview of drug delivery against cancer","volume":"130","author":"Shanmuganathan","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, W., Meng, Q., Li, Q., Liu, J., Zhou, M., Jin, Z., and Zhao, K. (2020). Chitosan derivatives and their application in biomedicine. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020487"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4852","DOI":"10.1002\/jps.21751","article-title":"New chitosan derivatives for the preparation of Rokitamycin loaded microspheres designed for ocular or nasal administration","volume":"98","author":"Rassu","year":"2009","journal-title":"J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mohammed, M.A., Syeda, J.T.M., Wasan, K.M., and Wasan, E.K. (2017). An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9040053"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/j.carbpol.2015.10.048","article-title":"Composite chitosan\/alginate hydrogel for controlled release of deferoxamine: A system to potentially treat iron dysregulation diseases","volume":"136","author":"Rassu","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1080\/10717544.2017.1399305","article-title":"Chitosan and its derivatives as vehicles for drug delivery","volume":"24","author":"Huang","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.ijbiomac.2016.05.054","article-title":"Why Chitosan? From properties to perspective of mucosal drug delivery","volume":"91","author":"Kumar","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hong, S.C., Yoo, S.Y., Kim, H., and Lee, J. (2017). Chitosan-based multifunctional platforms for local delivery of therapeutics. Mar. Drugs, 15.","DOI":"10.3390\/md15030060"},{"key":"ref_47","first-page":"765","article-title":"Recent advances of chitosan nanoparticles as drug carriers","volume":"6","author":"Wang","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/j.addr.2004.02.014","article-title":"Nanoparticle and targeted systems for cancer therapy","volume":"56","author":"Blanchette","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Thomas, T.J., Tajmir-Riahi, H.A., and Pillai, C.K.S. (2019). Biodegradable Polymers for Gene Delivery. Molecules, 24.","DOI":"10.3390\/molecules24203744"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1002\/iub.2252","article-title":"The potential role of chitosan-based nanoparticles as drug delivery systems in pancreatic cancer","volume":"72","author":"Sadoughi","year":"2020","journal-title":"IUBMB Life"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Arg\u00fcelles-Monal, W.M., Lizardi-Mendoza, J., Fern\u00e1ndez-Quiroz, D., Recillas-Mota, M.T., and Montiel-Herrera, M. (2018). Chitosan derivatives: Introducing new functionalities with a controlled molecular architecture for innovative materials. Polymers, 10.","DOI":"10.20944\/preprints201803.0005.v1"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ejca.2006.08.029","article-title":"In vitro and in vivo suppression of hepatocellular carcinoma growth by chitosan nanoparticles","volume":"43","author":"Qi","year":"2007","journal-title":"Eur. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1016\/j.bmcl.2006.05.078","article-title":"In vivo antitumor activity of chitosan nanoparticles","volume":"16","author":"Qi","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_54","first-page":"5103","article-title":"Chitosan nanoparticles inhibit the growth of human hepatocellular carcinoma xenografts through an antiangiogenic mechanism","volume":"30","author":"Xu","year":"2010","journal-title":"Anticancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbagen.2004.11.009","article-title":"Depolymerized products of chitosan as potent inhibitors of tumor-induced angiogenesis","volume":"1722","author":"Tharanathan","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.carbpol.2017.04.097","article-title":"Chitosan nanoparticles from marine squid protect liver cells against N-diethylnitrosoamine-induced hepatocellular carcinoma","volume":"171","author":"Subhapradha","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Elkeiy, M.M., and Khamis, A.A. (2018). Chitosan nanoparticles from Artemia salina inhibit progression of hepatocellular carcinoma in vitro and in vivo. Environ. Sci. Pollut. Res., 1\u201313.","DOI":"10.1007\/s11356-018-3339-6"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.toxrep.2018.06.002","article-title":"Crosstalk between GSK-3, c-Fos, NF\u03baB and TNF-\u03b1 signaling pathways play an ambitious role in chitosan nanoparticles cancer therapy","volume":"5","author":"Kadry","year":"2018","journal-title":"Toxicol. Rep."},{"key":"ref_59","first-page":"395","article-title":"Biological effects of irradiating hepatocellular carcinoma cells by internal exposure with 125I-labeled 5-Iodo-2\u2032-Deoxyuridine-chitosan drug loading nanoparticles","volume":"29","author":"Yang","year":"2014","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"111","DOI":"10.7785\/tcrt.2012.500404","article-title":"Synthesis and evaluation of hydroxycamptothecin encapsulated chitosan nanospheres for the treatment of liver cancer technology in cancer research and treatment","volume":"14","author":"Han","year":"2015","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17904","DOI":"10.1038\/srep17904","article-title":"CD147 monoclonal antibody mediated by chitosan nanoparticles loaded with \u03b1-hederin enhances antineoplastic activity and cellular uptake in liver cancer cells","volume":"5","author":"Zhu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.bbrc.2017.10.156","article-title":"Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53\/PRC1 pathway","volume":"495","author":"Ye","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ejpb.2014.04.016","article-title":"Improved antitumor activity and reduced cardiotoxicity of epirubicin using hepatocyte-targeted nanoparticles combined with tocotrienols against hepatocellular carcinoma in mice","volume":"88","author":"Nasr","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1080\/21691401.2017.1422130","article-title":"Chitosan\/poly (lactic acid)-coated piceatannol nanoparticles exert an in vitro apoptosis activity on liver, lung and breast cancer cell lines","volume":"46","author":"Dhanapal","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.nano.2017.09.004","article-title":"Uptake and bioreactivity of charged chitosan-coated superparamagnetic nanoparticles as promising contrast agents for magnetic resonance imaging","volume":"14","author":"Kania","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.carbpol.2010.12.042","article-title":"Effect of chitosan coating in overcoming the phagocytosis of insulin loaded solid lipid nanoparticles by mononuclear phagocyte system","volume":"84","author":"Sarmento","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/sj.bjc.6690708","article-title":"The asialoglycoprotein receptor in human hepatocellular carcinomas: Its expression on proliferating cells","volume":"81","author":"Fiume","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jconrel.2015.02.022","article-title":"Asialoglycoprotein receptor mediated hepatocyte targeting\u2014Strategies and applications","volume":"203","author":"Devarajan","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1016\/j.biomaterials.2003.10.063","article-title":"Galactosylated chitosan\/DNA nanoparticles prepared using water-soluble chitosan as a gene carrier","volume":"25","author":"Kim","year":"2004","journal-title":"Biomaterials"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e47115","DOI":"10.1371\/journal.pone.0047115","article-title":"5-fluorouracil nanoparticles inhibit hepatocellular carcinoma via activation of the p53 pathway in the orthotopic transplant mouse model","volume":"7","author":"Cheng","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6076","DOI":"10.3748\/wjg.v18.i42.6076","article-title":"Galactosylated chitosan\/5-fluorouracil nanoparticles inhibit mouse hepatic cancer growth and its side effects","volume":"18","author":"Cheng","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.4161\/cbt.22001","article-title":"Preliminary pharmacology of galactosylated chitosan\/5-fluorouracil nanoparticles and its inhibition of hepatocellular carcinoma in mice","volume":"13","author":"Cheng","year":"2012","journal-title":"Cancer Biol. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"15755","DOI":"10.3390\/ijms140815755","article-title":"Galactosylated chitosan oligosaccharide nanoparticles for hepatocellular carcinoma cell-targeted delivery of adenosine triphosphate","volume":"14","author":"Zhu","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.carbpol.2013.01.014","article-title":"Galactosylated chitosan\u2013polycaprolactone nanoparticles for hepatocyte-targeted delivery of curcumin","volume":"94","author":"Zhou","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/bph.13621","article-title":"Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases","volume":"174","author":"Kunnumakkara","year":"2017","journal-title":"Br. J. Pharm."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"22149","DOI":"10.1038\/srep22149","article-title":"Asialoglycoprotein receptor magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma","volume":"6","author":"Xue","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.nano.2018.09.002","article-title":"Galactosylated chitosan triptolide nanoparticles for overcoming hepatocellular carcinoma: Enhanced therapeutic efficacy, low toxicity, and validated network regulatory mechanisms","volume":"15","author":"Zhang","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Nair, A.B., Shah, J., Al-Dhubiab, B.E., Patel, S.S., Morsy, M.A., Patel, V., Chavda, V., Jacob, S., Sreeharsha, N., and Shinu, P. (2019). Development of asialoglycoprotein receptor-targeted nanoparticles for selective delivery of gemcitabine to hepatocellular carcinoma. Molecules, 24.","DOI":"10.3390\/molecules24244566"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1002\/ptr.2362","article-title":"Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds","volume":"22","author":"Asl","year":"2008","journal-title":"Phytother. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/ptr.2295","article-title":"Antiviral effects of Glycyrrhiza species","volume":"22","author":"Fiore","year":"2008","journal-title":"Phytother. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ijpharm.2008.03.039","article-title":"Glycyrrhizin surface-modified chitosan nanoparticles for hepatocyte targeted delivery","volume":"359","author":"Lin","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/jphp.12235","article-title":"Glycyrrhizin conjugated chitosan nanoparticles for hepatocyte-targeted delivery of lamivudine","volume":"66","author":"Mishra","year":"2014","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.3109\/10717544.2014.977460","article-title":"Development, optimization and characterization of glycyrrhetinic acid\u2013chitosan nanoparticles of atorvastatin for liver targeting","volume":"23","author":"Rohilla","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4748","DOI":"10.1016\/j.biomaterials.2010.02.042","article-title":"Glycyrrhetinic acid-modified chitosan\/poly(ethylene glycol) nanoparticles for liver-targeted delivery","volume":"31","author":"Tian","year":"2010","journal-title":"Biomaterials"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.3109\/03639040902939197","article-title":"Preparation and evaluation of N-caproyl chitosan nanoparticles surface modified with glycyrrhizin for hepatocyte targeting","volume":"35","author":"Lin","year":"2009","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7594","DOI":"10.1016\/j.biomaterials.2012.06.072","article-title":"Glycyrrhizin-modified O-carboxymethyl chitosan nanoparticles as drug vehicles targeting hepatocellular carcinoma","volume":"33","author":"Shi","year":"2012","journal-title":"Biomaterials"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2217\/nnm-2018-0455","article-title":"Biodistribution and biocompatibility of glycyrrhetinic acid and galactose-modified chitosan nanoparticles as a novel targeting vehicle for hepatocellular carcinoma","volume":"15","author":"Li","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.7150\/thno.16236","article-title":"Mouse IP-10 gene delivered by folate-modified chitosan nanoparticles and dendritic\/tumor cells fusion vaccine effectively inhibit the growth of hepatocellular carcinoma in mice","volume":"7","author":"Hu","year":"2017","journal-title":"Theranostics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1166\/jbn.2014.2051","article-title":"Anti-tumor immune response of folate-conjugated chitosan nanoparticles containing the IP-10 gene in mice with hepatocellular carcinoma","volume":"10","author":"Lai","year":"2014","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_90","first-page":"1489","article-title":"Therapeutic efficiency of folated poly(ethylene glycol)-chitosan-graft-polyethylenimine-Pdcd4 complexes in H-ras12V mice with liver cancer","volume":"8","author":"Kim","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.ejmech.2008.04.021","article-title":"Targeting cancer cells with biotin-dendrimer conjugates","volume":"44","author":"Yang","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.biomaterials.2011.09.064","article-title":"Gold nanoparticles surface functionalized with paclitaxel drug and biotin receptor as theranostic agents for cancer therapy","volume":"33","author":"Heo","year":"2012","journal-title":"Biomaterials"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"59068","DOI":"10.18632\/oncotarget.19146","article-title":"Anti-cancer efficacy of biotinylated chitosan nanoparticles in liver cancer","volume":"8","author":"Cheng","year":"2017","journal-title":"Oncotarget"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.ijpharm.2013.05.007","article-title":"Trans-resveratrol loaded chitosan nanoparticles modified with biotin and avidin to target hepatic carcinoma","volume":"452","author":"Bu","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.4161\/cbt.4.12.2273","article-title":"Isolating human antibody against human hepatocellular carcinoma by guided-selection","volume":"4","author":"Bao","year":"2005","journal-title":"Cancer Biol. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.carbpol.2011.02.018","article-title":"N,N,N-Trimethyl chitosan nanoparticles for the delivery of monoclonal antibodies against hepatocellular carcinoma cells","volume":"85","author":"Vongchan","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/17458080.2010.489580","article-title":"Preparation of a novel liver-targeting nanoparticle of norcantharidin derivative and evaluation of its anti-tumor activity","volume":"6","author":"Hu","year":"2011","journal-title":"J. Exp. Nanosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/j.nano.2012.01.009","article-title":"N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy","volume":"8","author":"Guan","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ejpb.2006.07.016","article-title":"Nanoparticles based on N-trimethylchitosan: Evaluation of absorption properties using in vitro (Caco-2 cells) and ex vivo (excised rat jejunum) models","volume":"65","author":"Sandri","year":"2007","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S1499-3872(15)60336-8","article-title":"Development of hybrid-type modified chitosan derivative nanoparticles for the intracellular delivery of midkine-siRNA in hepatocellular carcinoma cells","volume":"14","author":"Zhong","year":"2015","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5965","DOI":"10.1016\/j.biomaterials.2014.03.088","article-title":"Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy","volume":"35","author":"Zhu","year":"2014","journal-title":"Biomaterials"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1016\/j.biomaterials.2009.12.019","article-title":"Lactose mediated liver targeting effect observed by ex vivo imaging technology","volume":"31","author":"Ma","year":"2010","journal-title":"Biomaterials"},{"key":"ref_103","first-page":"7833","article-title":"Preparation and characterization of the Adriamycin loaded amphiphilic chitosan nanoparticles and their application in the treatment of liver cancer","volume":"17","author":"Kou","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1021\/acs.molpharmaceut.6b00507","article-title":"Precise targeting of liver tumor using glycol chitosan nanoparticles: Mechanisms, key factors, and their implications","volume":"13","author":"Na","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1021\/mp300009u","article-title":"A prodrug nanoparticle approach for the oral delivery of a hydrophilic peptide, leucine(5)-enkephalin, to the brain","volume":"9","author":"Lalatsa","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1021\/mp300068j","article-title":"Delivery of peptides to the blood and brain after oral uptake of quaternary ammonium palmitoyl glycol chitosan nanoparticles","volume":"9","author":"Lalatsa","year":"2012","journal-title":"Mol. Pharm."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/10\/5\/870\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:09:31Z","timestamp":1760364571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/10\/5\/870"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,30]]},"references-count":106,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["nano10050870"],"URL":"https:\/\/doi.org\/10.3390\/nano10050870","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,30]]}}}