{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:05:52Z","timestamp":1788303952050,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Introduction:<\/jats:bold>\n                    Icaritin (ICT), a promising anti-hepatocellular carcinoma (HCC) prenylated flavonoid, is hindered from being applied due to its low water solubility and high lipophilicity in poorly differentiated HCC which is associated with upregulation of CD44 isoforms. Thus, hyaluronic acid (HA), a natural polysaccharide with high binding ability to CD44 receptors, was used to formulate a modified liposome as a novel targeted ICT-delivery system for HCC treatment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    The ICT-Liposomes (Lip-ICT) with and without HA were prepared by a combined method of thin-film dispersion and post-insertion. The particle size, polydispersity (PDI), zeta potential, encapsulation efficacy (%EE), drug loading content (%DLC), and\n                    <jats:italic>in vitro<\/jats:italic>\n                    drug release profiles were investigated for physicochemical properties, whereas MTT assay was used to assess cytotoxic effects on HCC cells, HepG2, and Huh7 cells. Tumor bearing nude mice were used to evaluate the inhibitory effect of HA-Lip-ICT and Lip-ICT\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Lip-ICT and HA-Lip-ICT had an average particle size of 171.2 \u00b1 1.2\u00a0nm and 208.0 \u00b1 3.2 nm, with a zeta potential of \u221213.9 \u00b1 0.83 and \u221224.8 \u00b1 0.36, respectively. The PDI resulted from Lip-ICT and HA-Lip-ICT was 0.28 \u00b1 0.02 and 0.26 \u00b1 0.02, respectively. HA-Lip-ICT demonstrated higher\n                    <jats:italic>in vitro<\/jats:italic>\n                    drug release when pH was dropped from 7.4 to 5.5, The 12-h release rate of ICT from liposomes increased from 30% at pH7.4 to more than 60% at pH5.5. HA-Lip-ICT displayed higher toxicity than Lip-ICT in both HCC cells, especially Huh7with an IC\n                    <jats:sup>50<\/jats:sup>\n                    of 34.15 \u00b1 2.11\u00a0\u03bcM. The\n                    <jats:italic>in vivo<\/jats:italic>\n                    tissue distribution and anti-tumor experiments carried on tumor bearing nude mice indicated that HA-Lip- ICT exhibited higher tumor accumulation and achieved a tumor growth inhibition rate of 63.4%.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Discussion:<\/jats:bold>\n                    The nano-sized Lip-ICT was able to prolong the drug release time and showed long-term killing HCC cells ability. Following conjugation with HA, HA-Lip-ICT exhibited higher cytotoxicity, stronger tumor targeting, and tumor suppression abilities than Lip-ICT attributed to HA-CD44 ligand-receptor interaction, increasing the potential of ICT to treat HCC.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2024.1437515","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T02:24:41Z","timestamp":1720751081000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Hyaluronic acid-modified liposomes Potentiated in-vivo anti-hepatocellular carcinoma of icaritin"],"prefix":"10.3389","volume":"15","author":[{"given":"Xiaoduan","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongbing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawitree","family":"Chiampanichayakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songyot","family":"Anuchapreeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Singkome","family":"Tima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"426","DOI":"10.34172\/apb.2021.050","article-title":"Understanding hyaluronan receptor (CD44) interaction, HA-CD44 activated potential targets in cancer therapeutics","volume":"11","author":"Akim","year":"2021","journal-title":"Adv. Pharm. Bull."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.5935\/scd1984-8773.2021130006","article-title":"The importance of interaction between hyaluronic acid and CD44 receptor","volume":"13","author":"Antonio","year":"2021","journal-title":"Surg. Cosmet. dermatology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1002\/cam4.1968","article-title":"CD44 standard isoform is involved in maintenance of cancer stem cells of a hepatocellular carcinoma cell line","volume":"8","author":"Asai","year":"2019","journal-title":"Cancer Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"109124","DOI":"10.1016\/j.cbi.2020.109124","article-title":"Molecular and cellular basis of the anticancer activity of the prenylated flavonoid icaritin in hepatocellular carcinoma","volume":"325","author":"Bailly","year":"2020","journal-title":"Chemico-Biological Interact."},{"key":"B5","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.nantod.2014.04.008","article-title":"Challenges associated with penetration of nanoparticles across cell and tissue barriers: a review of current status and future prospects","volume":"9","author":"Barua","year":"2014","journal-title":"Nano today"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.3390\/molecules27031062","article-title":"Hyaluronated and PEGylated liposomes as a potential drug-delivery strategy to specifically target liver cancer and inflammatory cells","volume":"27","author":"Cannito","year":"2022","journal-title":"Molecules"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.phymed.2012.05.017","article-title":"Oral absorption and excretion of icaritin, an aglycone and also active metabolite of prenylflavonoids from the Chinese medicine Herba Epimedii in rats","volume":"19","author":"Chang","year":"2012","journal-title":"Phytomedicine"},{"key":"B8","doi-asserted-by":"publisher","first-page":"115","DOI":"10.3322\/caac.21338","article-title":"Cancer statistics in China, 2015","volume":"66","author":"Chen","year":"2016","journal-title":"CA A Cancer J. Clin."},{"key":"B9","doi-asserted-by":"publisher","first-page":"921","DOI":"10.2147\/ijn.S53310","article-title":"GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation","volume":"9","author":"Cheng","year":"2014","journal-title":"Int. J. Nanomedicine"},{"key":"B10","doi-asserted-by":"publisher","first-page":"119706","DOI":"10.1016\/j.biomaterials.2019.119706","article-title":"Advanced liposome-loaded scaffolds for therapeutic and tissue engineering applications","volume":"232","author":"Cheng","year":"2020","journal-title":"Biomaterials"},{"key":"B11","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.jep.2005.05.011","article-title":"Plants as a source of anti-cancer agents","volume":"100","author":"Cragg","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"5858","DOI":"10.1021\/nn4010796","article-title":"Smart pH-sensitive and temporal-controlled polymeric micelles for effective combination therapy of doxorubicin and disulfiram","volume":"7","author":"Duan","year":"2013","journal-title":"ACS Nano"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1053\/j.gastro.2007.04.061","article-title":"Hepatocellular carcinoma: epidemiology and molecular carcinogenesis","volume":"132","author":"El-Serag","year":"2007","journal-title":"Gastroenterology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/s0168-8278(00)80192-0","article-title":"Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, p53 expression, and patient survival","volume":"32","author":"Endo","year":"2000","journal-title":"J. Hepatology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1002\/eji.201948225","article-title":"Icaritin promotes tumor T\u2010cell infiltration and induces antitumor immunity in mice","volume":"49","author":"Hao","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"800481","DOI":"10.3389\/fphar.2021.800481","article-title":"CD44-Targeted nanocarrier for cancer therapy","volume":"12","author":"Kesharwani","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"8525","DOI":"10.1021\/nn300289u","article-title":"Consecutive targetable smart nanoprobe for molecular recognition of cytoplasmic microRNA in metastatic breast cancer","volume":"6","author":"Kim","year":"2012","journal-title":"ACS Nano"},{"key":"B18","doi-asserted-by":"publisher","first-page":"264","DOI":"10.3390\/pharmaceutics12030264","article-title":"Liposomes for enhanced bioavailability of water-insoluble drugs: in vivo evidence and recent approaches","volume":"12","author":"Lee","year":"2020","journal-title":"Pharmaceutics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1080\/10717544.2019.1580797","article-title":"Dual-functionalized liposome by co-delivery of paclitaxel with sorafenib for synergistic antitumor efficacy and reversion of multidrug resistance","volume":"26","author":"Lei","year":"2019","journal-title":"Drug Deliv."},{"key":"B20","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1186\/s12885-021-08043-9","article-title":"Icaritin promotes apoptosis and inhibits proliferation by down-regulating AFP gene expression in hepatocellular carcinoma","volume":"21","author":"Li","year":"2021","journal-title":"BMC Cancer"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.1021\/mp300688t","article-title":"A strategy for the improvement of the bioavailability and antiosteoporosis activity of BCS IV flavonoid glycosides through the formulation of their lipophilic aglycone into nanocrystals","volume":"10","author":"Li","year":"2013","journal-title":"Mol. Pharm."},{"key":"B22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.biomaterials.2015.08.035","article-title":"Tumor-specific penetrating peptides-functionalized hyaluronic acid-d-\u03b1-tocopheryl succinate based nanoparticles for multi-task delivery to invasive cancers","volume":"71","author":"Liang","year":"2015","journal-title":"Biomaterials"},{"key":"B23","doi-asserted-by":"publisher","first-page":"117572","DOI":"10.1016\/j.carbpol.2020.117572","article-title":"Inhibition of growth and metastasis of breast cancer by targeted delivery of 17-hydroxy-jolkinolide B via hyaluronic acid-coated liposomes","volume":"257","author":"Liu","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"B24","doi-asserted-by":"publisher","first-page":"105799","DOI":"10.1016\/j.intimp.2019.105799","article-title":"Icariin and icaritin ameliorated hippocampus neuroinflammation via mediating HMGB1 expression in social defeat model in mice","volume":"75","author":"Liu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"22800","DOI":"10.18632\/oncotarget.15205","article-title":"Identification of sphingosine kinase 1 (SphK1) as a primary target of icaritin in hepatocellular carcinoma cells","volume":"8","author":"Lu","year":"2017","journal-title":"Oncotarget"},{"key":"B26","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s40779-022-00433-9","article-title":"Nanomedicine\u2010boosting icaritin-based immunotherapy of advanced hepatocellular carcinoma","volume":"9","author":"Lu","year":"2022","journal-title":"Mil. Med. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e131758","DOI":"10.5812\/ijpr-131758","article-title":"Hyaluronic acid-modified liposomes for ursolic acid-targeted delivery treat lung cancer based on p53\/ARTS-mediated mitochondrial apoptosis","volume":"22","author":"Ma","year":"2023","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"B28","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.addr.2019.07.010","article-title":"Nanocarrier-based systems for targeted and site specific therapeutic delivery","volume":"144","author":"Majumder","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"6817","DOI":"10.1002\/jcp.29576","article-title":"Hyaluronic acid-decorated liposomal nanoparticles for targeted delivery of 5-fluorouracil into HT-29 colorectal cancer cells","volume":"235","author":"Mansoori","year":"2020","journal-title":"J. Cell. Physiology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3389\/fimmu.2015.00201","article-title":"Interactions between hyaluronan and its receptors (CD44, RHAMM) regulate the activities of inflammation and cancer","volume":"6","author":"Misra","year":"2015","journal-title":"Front. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.2217\/nnm-2016-5000","article-title":"Lipid-based nanosystems for CD44 targeting in cancer treatment: recent significant advances, ongoing challenges and unmet needs","volume":"11","author":"Nascimento","year":"2016","journal-title":"Nanomedicine (Lond)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1021\/jm0704090","article-title":"Natural products as leads to potential drugs: an old process or the new hope for drug discovery?","volume":"51","author":"Newman","year":"2008","journal-title":"J. Med. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/s0163-7827(01)00020-0","article-title":"Cholesterol interactions with phospholipids in membranes","volume":"41","author":"Ohvo-Rekil\u00e4","year":"2002","journal-title":"Prog. Lipid Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1517\/17425241003730399","article-title":"Nanostructured hyaluronic acid-based materials for active delivery to cancer","volume":"7","author":"Ossipov","year":"2010","journal-title":"Expert Opin. Drug Deliv."},{"key":"B36","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.bbamem.2012.10.013","article-title":"FTIR, (1)H NMR and EPR spectroscopy studies on the interaction of flavone apigenin with dipalmitoylphosphatidylcholine liposomes","volume":"1828","author":"Pawlikowska-Pawl\u0119ga","year":"2013","journal-title":"Biochimica Biophysica Acta"},{"key":"B38","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.jconrel.2016.03.012","article-title":"Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation","volume":"229","author":"Ravar","year":"2016","journal-title":"J. Control. Release"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e22175","DOI":"10.1002\/ddr.22175","article-title":"New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives","volume":"85","author":"Reyes-Hern\u00e1ndez","year":"2024","journal-title":"Drug Dev. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.3390\/pharmaceutics14081566","article-title":"Nanocarriers: a reliable tool for the delivery of anticancer drugs","volume":"14","author":"Sabit","year":"2022","journal-title":"Pharmaceutics"},{"key":"B41","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nrgastro.2013.143","article-title":"Chemopreventive strategies in hepatocellular carcinoma","volume":"11","author":"Singh","year":"2014","journal-title":"Nat. Rev. Gastroenterology Hepatology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"101179","DOI":"10.1016\/j.jddst.2019.101179","article-title":"Hyaluronic acid modified liposomes for targeted delivery of doxorubicin and paclitaxel to CD44 overexpressing tumor cells with improved dual-drugs synergistic effect","volume":"53","author":"Song","year":"2019","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3390\/pharmaceutics12090837","article-title":"Recent advances in nanocarrier-assisted therapeutics delivery systems","volume":"12","author":"Su","year":"2020","journal-title":"Pharmaceutics"},{"key":"B44","doi-asserted-by":"publisher","first-page":"7861","DOI":"10.3390\/molecules15117861","article-title":"Herba Epimedii: anti-oxidative properties and its medical implications","volume":"15","author":"Sze","year":"2010","journal-title":"Molecules"},{"key":"B45","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.ijpharm.2014.05.027","article-title":"Study on intralymphatic-targeted hyaluronic acid-modified nanoliposome: influence of formulation factors on the lymphatic targeting","volume":"471","author":"Tiantian","year":"2014","journal-title":"Int. J. Pharm."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1093\/carcin\/bgs110","article-title":"A novel prenylflavone restricts breast cancer cell growth through AhR-mediated destabilization of ER\u03b1 protein","volume":"33","author":"Tiong","year":"2012","journal-title":"Carcinogenesis"},{"key":"B47","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA A Cancer J. Clin."},{"key":"B48","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.carbpol.2014.08.026","article-title":"Hyaluronic acid-coated solid lipid nanoparticles for targeted delivery of vorinostat to CD44 overexpressing cancer cells","volume":"114","author":"Tran","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"B49","doi-asserted-by":"publisher","first-page":"115981","DOI":"10.1016\/j.carbpol.2020.115981","article-title":"Hyaluronic acid-modified liposomal honokiol nanocarrier: enhance anti-metastasis and antitumor efficacy against breast cancer","volume":"235","author":"Wang","year":"","journal-title":"Carbohydr. Polym."},{"key":"B50","doi-asserted-by":"publisher","first-page":"111261","DOI":"10.1016\/j.msec.2020.111261","article-title":"Hyaluronic acid-shelled, peptide drug conjugate-cored nanomedicine for the treatment of hepatocellular carcinoma","volume":"117","author":"Wang","year":"","journal-title":"Mater. Sci. Eng. C"},{"key":"B51","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1080\/13880209.2019.1628073","article-title":"Induction of ROS and DNA damage-dependent senescence by icaritin contributes to its antitumor activity in hepatocellular carcinoma cells","volume":"57","author":"Wang","year":"2019","journal-title":"Pharm. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.jconrel.2007.05.011","article-title":"Preparation and evaluation of paclitaxel-loaded PEGylated immunoliposome","volume":"120","author":"Yang","year":"2007","journal-title":"J. Control. Release"},{"key":"B53","doi-asserted-by":"publisher","first-page":"4860268","DOI":"10.1155\/2019\/4860268","article-title":"Icaritin: a novel natural candidate for hematological malignancies therapy","volume":"2019","author":"Yang","year":"2019","journal-title":"BioMed Res. Int."},{"key":"B54","doi-asserted-by":"publisher","first-page":"3950","DOI":"10.3892\/ol.2020.11496","article-title":"Icaritin enhances the efficacy of cetuximab against triple-negative breast cancer cells","volume":"19","author":"Yin","year":"2020","journal-title":"Oncol. Lett."},{"key":"B55","first-page":"5","article-title":"Antitumor effects of icaritin and the molecular mechanisms","volume":"29","author":"Zhang","year":"2020","journal-title":"Discov. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1016\/j.apsb.2021.03.033","article-title":"Influencing factors and strategies of enhancing nanoparticles into tumors in vivo","volume":"11","author":"Zhang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"B57","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.colsurfb.2014.02.036","article-title":"Storage stability and skin permeation of vitamin C liposomes improved by pectin coating","volume":"117","author":"Zhou","year":"2014","journal-title":"Colloids Surfaces B Biointerfaces"},{"key":"B58","doi-asserted-by":"publisher","first-page":"16185","DOI":"10.1038\/srep16185","article-title":"Ailanthone inhibits Huh7 cancer cell growth via cell cycle arrest and apoptosis in vitro and in vivo","volume":"5","author":"Zhuo","year":"2015","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1437515\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T02:24:47Z","timestamp":1720751087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1437515\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":58,"alternative-id":["10.3389\/fphar.2024.1437515"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1437515","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,11]]},"article-number":"1437515"}}