{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:18:33Z","timestamp":1789442313992,"version":"build-2803163510"},"reference-count":109,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Liver cancer is one of the most common causes of cancer mortality worldwide. Chemotherapy and radiotherapy are the conventional therapies generally employed in patients with liver tumors. The major issue associated with the administration of chemotherapeutics is their high toxicity and lack of selectivity, leading to systemic toxicity that can be detrimental to the patient\u2019s quality of life. An important approach to the development of original liver-targeted therapeutic products takes advantage of the employment of biologically active ligands able to bind specific receptors on the cytoplasmatic membranes of liver cells. In this perspective, glycyrrhetinic acid (GA), a pentacyclic triterpenoid present in roots and rhizomes of licorice, has been used as a ligand for targeting the liver due to the expression of GA receptors on the sinusoidal surface of mammalian hepatocytes, so it may be employed to modify drug delivery systems (DDSs) and obtain better liver or hepatocyte drug uptake and efficacy. In the current review, we focus on the most recent and interesting research advances in the development of GA-based hybrid compounds and DDSs developed for potential employment as efficacious therapeutic options for the treatment of hepatic cancer.<\/jats:p>","DOI":"10.3390\/molecules27061775","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T01:53:54Z","timestamp":1646790834000},"page":"1775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Recent Advances in Glycyrrhetinic Acid-Functionalized Biomaterials for Liver Cancer-Targeting Therapy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6135-3892","authenticated-orcid":false,"given":"Antonio","family":"Speciale","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-1731","authenticated-orcid":false,"given":"Claudia","family":"Muscar\u00e0","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8841-589X","authenticated-orcid":false,"given":"Maria Sofia","family":"Molonia","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Cristani","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8954-4797","authenticated-orcid":false,"given":"Francesco","family":"Cimino","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-3596","authenticated-orcid":false,"given":"Antonella","family":"Saija","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"256","DOI":"10.21037\/jgo.2016.09.07","article-title":"Hepatocellular carcinoma (HCC): Beyond sorafenib\u2014chemotherapy","volume":"8","author":"Kim","year":"2017","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.4251\/wjgo.v13.i12.2038","article-title":"Current status of first-line therapy, anti-angiogenic therapy and its combinations of other agents for unresectable hepatocellular carcinoma","volume":"13","author":"Alqahtani","year":"2021","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41571-021-00573-2","article-title":"Immunotherapies for hepatocellular carcinoma","volume":"19","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1002\/cam4.4521","article-title":"The role of mesenchymal stem cells in the occurrence, development, and therapy of hepatocellular carcinoma","volume":"11","author":"Zhang","year":"2022","journal-title":"Cancer Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.2147\/IJN.S115727","article-title":"Ligand-based targeted therapy: A novel strategy for hepatocellular carcinoma","volume":"11","author":"Li","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.jtbi.2005.12.022","article-title":"Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: Clinical implications and therapeutic targeting strategies","volume":"241","author":"McDougall","year":"2006","journal-title":"J. Theor. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0065-2571(00)00013-3","article-title":"The enhanced permeability and retention (EPR) effect in tumor vasculature: The key role of tumor-selective macromolecular drug targeting","volume":"41","author":"Maeda","year":"2001","journal-title":"Adv. Enzym. Regul."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1158\/1078-0432.CCR-07-1441","article-title":"Therapeutic Nanoparticles for Drug Delivery in Cancer","volume":"14","author":"Cho","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.addr.2008.08.005","article-title":"Active targeting schemes for nanoparticle systems in cancer therapeutics","volume":"60","author":"Byrne","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7571132","DOI":"10.1155\/2021\/7571132","article-title":"Glycyrrhiza Genus: Enlightening Phytochemical Components for Pharmacological and Health-Promoting Abilities","volume":"2021","author":"Quispe","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1002\/ptr.6178","article-title":"Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review","volume":"32","author":"Pastorino","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_14","unstructured":"M\u00e9rillon, J.-M., and Ramawat, K.G. (2018). The Pharmacological Activities of Glycyrrhizinic Acid (\u201cGlycyrrhizin\u201d) and Glycyrrhetinic Acid. Sweeteners: Pharmacology, Biotechnology, and Applications, Springer International Publishing."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1021\/acs.molpharmaceut.5b00677","article-title":"Glycyrrhetinic Acid Mediated Drug Delivery Carriers for Hepatocellular Carcinoma Therapy","volume":"13","author":"Cai","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1166\/jbn.2018.2638","article-title":"Glycyrrhetinic Acid Functionalized Nanoparticles for Drug Delivery to Liver Cancer","volume":"14","author":"Wu","year":"2018","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.phrs.2019.04.025","article-title":"Natural products in licorice for the therapy of liver diseases: Progress and future opportunities","volume":"144","author":"Li","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.etap.2017.05.003","article-title":"Cellular uptake mechanism and clearance kinetics of fluorescence-labeled glycyrrhetinic acid and glycyrrhetinic acid\u2013modified liposome in hepatocellular carcinoma cells","volume":"53","author":"Sun","year":"2017","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.2147\/IJN.S153944","article-title":"Hepatocellular carcinoma-targeted effect of configurations and groups of glycyrrhetinic acid by evaluation of its derivative-modified liposomes","volume":"13","author":"Sun","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0005-2736(91)90253-5","article-title":"Specific binding of glycyrrhetinic acid to the rat liver membrane","volume":"1066","author":"Negishi","year":"1991","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ab.2004.12.026","article-title":"Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay","volume":"338","author":"Parker","year":"2005","journal-title":"Anal. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s13277-014-2855-3","article-title":"Active radar guides missile to its target: Receptor-based targeted treatment of hepatocellular carcinoma by nanoparticulate systems","volume":"36","author":"Yan","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Xu, B., Wu, G.-R., Zhang, Q.-W., Yan, M.-M., Zhao, R., Xue, N.-N., Fang, K., Wang, H., Chen, M., and Guo, W.-B. (2017). An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents. Molecules, 22.","DOI":"10.3390\/molecules22060924"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1080\/17460441.2021.1956901","article-title":"Glycyrrhetinic acid: A promising scaffold for the discovery of anticancer agents","volume":"16","author":"Hussain","year":"2021","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_25","first-page":"4043","article-title":"Glycyrrhetinic acid and related compounds induce G1 arrest and apoptosis in human hepatocellular carcinoma HepG2","volume":"25","author":"Satomi","year":"2005","journal-title":"Anticancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11910","DOI":"10.1021\/jf503968k","article-title":"Glycyrrhetinic Acid Triggers a Protective Autophagy by Activation of Extracellular Regulated Protein Kinases in Hepatocellular Carcinoma Cells","volume":"62","author":"Tang","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","first-page":"215","article-title":"Glycyrrhetic acid (a metabolic substance and aglycon of glycyrrhizin) induces apoptosis in human hepatoma, promyelotic leukemia and stomach cancer cells","volume":"17","author":"Hibasami","year":"2006","journal-title":"Int. J. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1002\/ijc.27852","article-title":"18\u03b2-glycyrrhetinic acid inhibits hepatocellular carcinoma development by reversing hepatic stellate cell-mediated immunosuppression in mice","volume":"132","author":"Kuang","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3109\/10717544.2013.853850","article-title":"A wogonin-loaded glycyrrhetinic acid-modified liposome for hepatic targeting with anti-tumor effects","volume":"21","author":"Tian","year":"2013","journal-title":"Drug Deliv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1196\/annals.1322.025","article-title":"Intercellular Communication and Human Hepatocellular Carcinoma","volume":"1028","author":"Carruba","year":"2004","journal-title":"Ann. Acad. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s13046-020-01629-4","article-title":"Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma","volume":"39","author":"Feng","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.2174\/138161211796904803","article-title":"Mitochondrial Drug Targets in Cell Death and Cancer","volume":"17","author":"Linares","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1016\/j.bcp.2003.08.023","article-title":"Glycyrrhetinic acid-induced permeability transition in rat liver mitochondria","volume":"66","author":"Salvi","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bbabio.2004.05.012","article-title":"On the mechanism of mitochondrial permeability transition induction by glycyrrhetinic acid","volume":"1658","author":"Fiore","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1111\/j.1440-1746.2006.04643.x","article-title":"Modulation of mitochondrial membrane permeability in pathogenesis, autophagy and control of metabolism","volume":"22","author":"Lemasters","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bioorg.2018.12.036","article-title":"Mitochondria-targeted triphenylphosphonium conjugated glycyrrhetinic acid derivatives as potent anticancer drugs","volume":"85","author":"Jin","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Spivak, A., Nedopekina, D., Gubaidullin, R., Dubinin, M., and Belosludtsev, K. (2021). Conjugation of Natural Triterpenic Acids with Delocalized Lipophilic Cations: Selective Targeting Cancer Cell Mitochondria. J. Pers. Med., 11.","DOI":"10.3390\/jpm11060470"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1039\/C9MD00572B","article-title":"TPP-based mitocans: A potent strategy for anticancer drug design","volume":"11","author":"Wang","year":"2020","journal-title":"RSC Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Micale, N., Molonia, M., Citarella, A., Cimino, F., Saija, A., Cristani, M., and Speciale, A. (2021). Natural Product-Based Hybrids as Potential Candidates for the Treatment of Cancer: Focus on Curcumin and Resveratrol. Molecules, 26.","DOI":"10.3390\/molecules26154665"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1039\/C9MD00246D","article-title":"Synthesis and antitumor activity of fluorouracil\u2013oleanolic acid\/ursolic acid\/glycyrrhetinic acid conjugates","volume":"10","author":"Liu","year":"2019","journal-title":"Med. Chem. Comm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6416","DOI":"10.1016\/j.bmcl.2010.09.070","article-title":"Synthesis and biological evaluation of furoxan-based nitric oxide-releasing derivatives of glycyrrhetinic acid as anti-hepatocellular carcinoma agents","volume":"20","author":"Lai","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"0300060520905985","DOI":"10.1177\/0300060520905985","article-title":"The regulation of nitric oxide in tumor progression and therapy","volume":"48","author":"Hu","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105233","DOI":"10.1016\/j.phrs.2020.105233","article-title":"The novel glycyrrhetinic acid\u2013tetramethylpyrazine conjugate TOGA induces anti-hepatocarcinogenesis by inhibiting the effects of tumor-associated macrophages on tumor cells","volume":"161","author":"Wang","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nocca, G., D\u2019Avenio, G., Amalfitano, A., Chronopoulou, L., Mordente, A., Palocci, C., and Grigioni, M. (2021). Controlled Release of 18-\u03b2-Glycyrrhetinic Acid from Core-Shell Nanoparticles: Effects on Cytotoxicity and Intracellular Concentration in HepG2 Cell Line. Materials, 14.","DOI":"10.3390\/ma14143893"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1166\/jbn.2018.2467","article-title":"Glycyrrhetinic Acid-Modified Norcantharidin Nanoparticles for Active Targeted Therapy of Hepatocellular Carcinoma","volume":"14","author":"Zhang","year":"2018","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1080\/03639045.2020.1825475","article-title":"Preparation, evaluation, and in vitro cytotoxicity studies of artesunate-loaded glycyrrhetinic acid decorated PEG-PLGA nanoparticles","volume":"46","author":"Pan","year":"2020","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.3892\/etm.2021.10578","article-title":"Preparation of docetaxel-loaded, glycyrrhetinic acid-modified nanoparticles and their liver-targeting and antitumor activity","volume":"22","author":"Xue","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"110682","DOI":"10.1016\/j.biopha.2020.110682","article-title":"Enhanced targeted delivery of adenine to hepatocellular carcinoma using glycyrrhetinic acid-functionalized nanoparticles in vivo and in vitro","volume":"131","author":"Wu","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"913654","DOI":"10.1155\/2013\/913654","article-title":"Glycyrrhetinic Acid-Poly(ethylene glycol)-glycyrrhetinic Acid Tri-Block Conjugates Based Self-Assembled Micelles for Hepatic Targeted Delivery of Poorly Water Soluble Drug","volume":"2013","author":"Wu","year":"2013","journal-title":"Sci. World J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.colsurfb.2018.11.082","article-title":"Glycyrrhetinic acid-conjugated polymeric prodrug micelles co-delivered with doxorubicin as combination therapy treatment for liver cancer","volume":"175","author":"Yang","year":"2019","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.2147\/DDDT.S81722","article-title":"A novel glycyrrhetinic acid-modified oxaliplatin liposome for liver-targeting and in vitro\/vivo evaluation","volume":"9","author":"Gao","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1080\/10717544.2018.1526227","article-title":"Antitumor activities of novel glycyrrhetinic acid-modified curcumin-loaded cationic liposomes in vitro and in H22 tumor-bearing mice","volume":"25","author":"Chang","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.2147\/IJN.S188971","article-title":"Liver-targeted liposomes for codelivery of curcumin and combretastatin A4 phosphate: Preparation, characterization, and antitumor effects","volume":"14","author":"Jiang","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_54","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":"2020","journal-title":"Nanomedicine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16019","DOI":"10.1021\/acsami.0c23137","article-title":"Co-Delivery of Curcumin and Capsaicin by Dual-Targeting Liposomes for Inhibition of aHSC-Induced Drug Resistance and Metastasis","volume":"13","author":"Qi","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2147\/IJN.S240359","article-title":"Dual-Ligand Functionalized Core-Shell Chitosan-Based Nanocarrier for Hepatocellular Carcinoma-Targeted Drug Delivery","volume":"15","author":"Hefnawy","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ijpharm.2017.03.065","article-title":"Insight into the role of dual-ligand modification in low molecular weight heparin based nanocarrier for targeted delivery of doxorubicin","volume":"523","author":"Du","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"153356","DOI":"10.1016\/j.phymed.2020.153356","article-title":"Novel Chinese Angelica Polysaccharide Biomimetic Nanomedicine to Curcumin Delivery for Hepatocellular Carcinoma Treatment and Immunomodulatory Effect","volume":"80","author":"Guo","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.canlet.2020.06.017","article-title":"Improved efficacy of doxorubicin delivery by a novel dual-ligand-modified liposome in hepatocellular carcinoma","volume":"489","author":"Li","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1007\/s13346-020-00894-2","article-title":"Thiolated polymer nanocarrier reinforced with glycyrrhetinic acid for targeted delivery of 5-fluorouracil in hepatocellular carcinoma","volume":"11","author":"Bhat","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.carbpol.2018.04.052","article-title":"Enhanced delivery of doxorubicin to the liver through self-assembled nanoparticles formed via conjugation of glycyrrhetinic acid to the hydroxyl group of hyaluronic acid","volume":"195","author":"Wang","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_62","first-page":"133","article-title":"Doxorubicin-loaded dual-functional hyaluronic acid nanoparticles: Preparation, characterization and antitumor efficacy in vitro and in vivo","volume":"19","author":"Tian","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1177\/0885328219841487","article-title":"Targeted pharmacokinetics of polymeric micelles modified with glycyrrhetinic acid and hydrazone bond in H22 tumor-bearing mice","volume":"34","author":"Zheng","year":"2019","journal-title":"J. Biomater. Appl."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"121003","DOI":"10.1016\/j.biomaterials.2021.121003","article-title":"Combined anti-hepatocellular carcinoma therapy inhibit drug-resistance and metastasis via targeting \u201csubstance P-hepatic stellate cells-hepatocellular carcinoma\u201d axis","volume":"276","author":"Li","year":"2021","journal-title":"Biomaterials"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9437","DOI":"10.2147\/IJN.S214528","article-title":"Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy","volume":"14","author":"Li","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1007\/s11095-015-1714-2","article-title":"Glycyrrhetinic Acid-Mediated Polymeric Drug Delivery Targeting the Acidic Microenvironment of Hepatocellular Carcinoma","volume":"32","author":"Zhang","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Edo, G., Fornaguera, C., Borr\u00f3s, S., and S\u00e1nchez-Garc\u00eda, D. (2020). Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX\/CPT-PEG for Targeting HepG2 Cells. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111048"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"325602","DOI":"10.1088\/1361-6528\/ab8c03","article-title":"Glycyrrhetinic acid modified MOFs for the treatment of liver cancer","volume":"31","author":"Li","year":"2020","journal-title":"Nanotechnology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1703306","DOI":"10.1002\/smll.201703306","article-title":"Glycyrrhetinic Acid Functionalized Graphene Oxide for Mitochondria Targeting and Cancer Treatment In Vivo","volume":"14","author":"Zhang","year":"2018","journal-title":"Small"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1166\/jnn.2015.9039","article-title":"Glycyrrhizin Conjugated Dendrimer and Multi-Walled Carbon Nanotubes for Liver Specific Delivery of Doxorubicin","volume":"15","author":"Chopdey","year":"2015","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"512","DOI":"10.3389\/fbioe.2020.00512","article-title":"Dual-Targeting Nanoparticle-Mediated Gene Therapy Strategy for Hepatocellular Carcinoma by Delivering Small Interfering RNA","volume":"8","author":"Zheng","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"116781","DOI":"10.1016\/j.carbpol.2020.116781","article-title":"Chitosan based pH-responsive polymeric prodrug vector for enhanced tumor targeted co-delivery of doxorubicin and siRNA","volume":"250","author":"Yana","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fphar.2019.00004","article-title":"Liver-Targeted Combination Therapy Basing on Glycyrrhizic Acid-Modified DSPE-PEG-PEI Nanoparticles for Co-delivery of Doxorubicin and Bcl-2 siRNA","volume":"10","author":"Tian","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1021\/acs.molpharmaceut.5b00879","article-title":"Codelivery of Doxorubicin and shAkt1 by Poly(ethylenimine)\u2013Glycyrrhetinic Acid Nanoparticles to Induce Autophagy-Mediated Liver Cancer Combination Therapy","volume":"13","author":"Wang","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Cao, M., Gao, Y., Zhan, M., Qiu, N., Piao, Y., Zhou, Z., and Shen, Y. (2019). Glycyrrhizin Acid and Glycyrrhetinic Acid Modified Polyethyleneimine for Targeted DNA Delivery to Hepatocellular Carcinoma. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205074"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.colsurfb.2018.07.067","article-title":"Improving dispersive property, biocompatibility and targeting gene transfection of graphene oxide by covalent attachment of polyamidoamine dendrimer and glycyrrhetinic acid","volume":"171","author":"Liu","year":"2018","journal-title":"Colloids Surfaces B Biointerfaces"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"105036","DOI":"10.1016\/j.ejps.2019.105036","article-title":"Glycyrrhetinic acid-modified graphene oxide mediated siRNA delivery for enhanced liver-cancer targeting therapy","volume":"139","author":"Qu","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1039\/C7OB03108D","article-title":"Nanoparticles based on glycyrrhetinic acid modified porphyrin for photodynamic therapy of cancer","volume":"16","author":"Wang","year":"2018","journal-title":"Org. Biomol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1021\/acs.biomac.0c01550","article-title":"Glycyrrhetinic Acid-Modified Silicon Phthalocyanine for Liver Cancer-Targeted Photodynamic Therapy","volume":"22","author":"Kim","year":"2020","journal-title":"Biomacromolecules"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"117284","DOI":"10.1016\/j.carbpol.2020.117284","article-title":"Carboxymethyl chitosan based redox-responsive micelle for near-infrared fluorescence image-guided photo-chemotherapy of liver cancer","volume":"253","author":"Yan","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.addr.2018.07.007","article-title":"Tumor targeting via EPR: Strategies to enhance patient responses","volume":"130","author":"Golombek","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"120807","DOI":"10.1016\/j.ijpharm.2021.120807","article-title":"PLGA-based nanomedicines manufacturing: Technologies overview and challenges in industrial scale-up","volume":"605","author":"Operti","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3109\/10717544.2010.500635","article-title":"Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil","volume":"17","author":"Yadav","year":"2010","journal-title":"Drug Deliv."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s40005-019-00439-x","article-title":"Biocompatibility, biodegradation and biomedical applications of poly(lactic acid)\/poly(lactic-co-glycolic acid) micro and nanoparticles","volume":"49","author":"Elmowafy","year":"2019","journal-title":"J. Pharm. Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"116968","DOI":"10.1016\/j.carbpol.2020.116968","article-title":"Design of chitosan-based particle systems: A review of the physicochemical foundations for tailored properties","volume":"250","author":"Ferreira","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"111824","DOI":"10.1016\/j.biopha.2021.111824","article-title":"New insight towards development of paclitaxel and docetaxel resistance in cancer cells: EMT as a novel molecular mechanism and therapeutic possibilities","volume":"141","author":"Ashrafizadeh","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"7146","DOI":"10.1016\/j.biomaterials.2014.04.108","article-title":"A PEG-Fmoc conjugate as a nanocarrier for paclitaxel","volume":"35","author":"Zhang","year":"2014","journal-title":"Biomaterials"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"747","DOI":"10.2147\/IJN.S40579","article-title":"Concepts and practices used to develop functional PLGA-based nanoparticulate systems","volume":"8","author":"Sah","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"De Leo, V., Milano, F., Agostiano, A., and Catucci, L. (2021). Recent Advancements in Polymer\/Liposome Assembly for Drug Delivery: From Surface Modifications to Hybrid Vesicles. Polymers, 13.","DOI":"10.3390\/polym13071027"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4504936","DOI":"10.1155\/2020\/4504936","article-title":"Antitumor Effects of Curcumin and Glycyrrhetinic Acid-Modified Curcumin-Loaded Cationic Liposome by Intratumoral Administration","volume":"2020","author":"Chang","year":"2020","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.7150\/thno.16358","article-title":"Targeting Negative Surface Charges of Cancer Cells by Multifunctional Nanoprobes","volume":"6","author":"Chen","year":"2016","journal-title":"Theranostics"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1369\/0022155413503662","article-title":"Expression of Asialoglycoprotein Receptor 1 in Human Hepatocellular Carcinoma","volume":"61","author":"Shi","year":"2013","journal-title":"J. Histochem. Cytochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jconrel.2015.02.022","article-title":"Asialoglycoprotein receptor mediated hepatocyte targeting\u2013Strategies and applications","volume":"203","author":"Devarajan","year":"2015","journal-title":"J. Control Release"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1080\/10408398.2013.772090","article-title":"Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review","volume":"56","author":"Srinivasan","year":"2015","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"709","DOI":"10.3389\/fcell.2020.00709","article-title":"Hepatic Stellate Cells and Hepatocarcinogenesis","volume":"8","author":"Barry","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Kaps, L., and Schuppan, D. (2020). Targeting Cancer Associated Fibroblasts in Liver Fibrosis and Liver Cancer Using Nanocarriers. Cells, 9.","DOI":"10.3390\/cells9092027"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1021\/acs.jafc.6b04805","article-title":"Capsaicin Inhibits Dimethylnitrosamine-Induced Hepatic Fibrosis by Inhibiting the TGF-\u03b21\/Smad Pathway via Peroxisome Proliferator-Activated Receptor Gamma Activation","volume":"65","author":"Choi","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jconrel.2018.08.030","article-title":"Exploiting the bioengineering versatility of lactobionic acid in targeted nanosystems and biomaterials","volume":"287","author":"Alonso","year":"2018","journal-title":"J. Control Release"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.tibtech.2011.12.002","article-title":"Exploiting cell surface thiols to enhance cellular uptake","volume":"30","author":"Torres","year":"2012","journal-title":"Trends Biotechnol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.addr.2019.04.007","article-title":"Thiolated polymers: Bioinspired polymers utilizing one of the most important bridging structures in nature","volume":"151\u2013152","author":"Leichner","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"71","DOI":"10.37349\/etat.2020.00005","article-title":"The impact of tumour pH on cancer progression: Strategies for clinical intervention","volume":"1","author":"Ward","year":"2020","journal-title":"Explor. Target. Anti-Tumor Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nrc3110","article-title":"Dysregulated pH: A perfect storm for cancer progression","volume":"11","author":"Webb","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.4155\/tde.13.120","article-title":"pH-sensitive drug-delivery systems for tumor targeting","volume":"4","author":"He","year":"2013","journal-title":"Ther. Deliv."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.dyepig.2018.04.008","article-title":"A pH-responsive organic photosensitizer specifically activated by cancer lysosomes","volume":"156","author":"Xue","year":"2018","journal-title":"Dye. Pigment."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1021\/acs.analchem.0c04644","article-title":"One Stone, Three Birds: pH Triggered Transformation of Aminopyronine and Iminopyronine Based Lysosome Targeting Viscosity Probe for Cancer Visualization","volume":"93","author":"Song","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/hep.29138","article-title":"Substance P increases liver fibrosis by differential changes in senescence of cholangiocytes and hepatic stellate cells","volume":"66","author":"Wan","year":"2017","journal-title":"Hepatology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1158\/0008-5472.CAN-03-3250","article-title":"Capsaicin Inhibits In Vitro and In Vivo Angiogenesis","volume":"64","author":"Min","year":"2004","journal-title":"Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"686303","DOI":"10.3389\/fchem.2021.686303","article-title":"Photodynamic Therapy for the Treatment and Diagnosis of Cancer\u2013A Review of the Current Clinical Status","volume":"9","author":"Gunaydin","year":"2021","journal-title":"Front. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"484","DOI":"10.3389\/fendo.2019.00484","article-title":"Licorice: From Pseudohyperaldosteronism to Therapeutic Uses","volume":"10","author":"Sabbadin","year":"2019","journal-title":"Front. Endocrinol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/6\/1775\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:34:07Z","timestamp":1760135647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/6\/1775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":109,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["molecules27061775"],"URL":"https:\/\/doi.org\/10.3390\/molecules27061775","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]}}}