{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:09:12Z","timestamp":1792789752284,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hunan Key Research and Development Program","award":["No. 2017SK2122"],"award-info":[{"award-number":["No. 2017SK2122"]}]},{"name":"Hunan Key Research and Development Program","award":["2021RC4064"],"award-info":[{"award-number":["2021RC4064"]}]},{"name":"Hunan Key Research and Development Program","award":["No. 19C1427"],"award-info":[{"award-number":["No. 19C1427"]}]},{"name":"Hunan Key Research and Development Program","award":["No. kq2014090"],"award-info":[{"award-number":["No. kq2014090"]}]},{"name":"Hunan Key Research and Development Program","award":["No. 2020JJ5417"],"award-info":[{"award-number":["No. 2020JJ5417"]}]},{"name":"Science and Technology Innovation Program of Hunan Province","award":["No. 2017SK2122"],"award-info":[{"award-number":["No. 2017SK2122"]}]},{"name":"Science and Technology Innovation Program of Hunan Province","award":["2021RC4064"],"award-info":[{"award-number":["2021RC4064"]}]},{"name":"Science and Technology Innovation Program of Hunan Province","award":["No. 19C1427"],"award-info":[{"award-number":["No. 19C1427"]}]},{"name":"Science and Technology Innovation Program of Hunan Province","award":["No. kq2014090"],"award-info":[{"award-number":["No. kq2014090"]}]},{"name":"Science and Technology Innovation Program of Hunan Province","award":["No. 2020JJ5417"],"award-info":[{"award-number":["No. 2020JJ5417"]}]},{"name":"General Project of Hunan Provincial Department of Education","award":["No. 2017SK2122"],"award-info":[{"award-number":["No. 2017SK2122"]}]},{"name":"General Project of Hunan Provincial Department of Education","award":["2021RC4064"],"award-info":[{"award-number":["2021RC4064"]}]},{"name":"General Project of Hunan Provincial Department of Education","award":["No. 19C1427"],"award-info":[{"award-number":["No. 19C1427"]}]},{"name":"General Project of Hunan Provincial Department of Education","award":["No. kq2014090"],"award-info":[{"award-number":["No. kq2014090"]}]},{"name":"General Project of Hunan Provincial Department of Education","award":["No. 2020JJ5417"],"award-info":[{"award-number":["No. 2020JJ5417"]}]},{"name":"Natural Science Foundation of Changsha","award":["No. 2017SK2122"],"award-info":[{"award-number":["No. 2017SK2122"]}]},{"name":"Natural Science Foundation of Changsha","award":["2021RC4064"],"award-info":[{"award-number":["2021RC4064"]}]},{"name":"Natural Science Foundation of Changsha","award":["No. 19C1427"],"award-info":[{"award-number":["No. 19C1427"]}]},{"name":"Natural Science Foundation of Changsha","award":["No. kq2014090"],"award-info":[{"award-number":["No. kq2014090"]}]},{"name":"Natural Science Foundation of Changsha","award":["No. 2020JJ5417"],"award-info":[{"award-number":["No. 2020JJ5417"]}]},{"name":"Natural Science Foundation of Hunan Province","award":["No. 2017SK2122"],"award-info":[{"award-number":["No. 2017SK2122"]}]},{"name":"Natural Science Foundation of Hunan Province","award":["2021RC4064"],"award-info":[{"award-number":["2021RC4064"]}]},{"name":"Natural Science Foundation of Hunan Province","award":["No. 19C1427"],"award-info":[{"award-number":["No. 19C1427"]}]},{"name":"Natural Science Foundation of Hunan Province","award":["No. kq2014090"],"award-info":[{"award-number":["No. kq2014090"]}]},{"name":"Natural Science Foundation of Hunan Province","award":["No. 2020JJ5417"],"award-info":[{"award-number":["No. 2020JJ5417"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cantharidin (CTD) is the major component of anticancer drugs obtained from Mylabris Cichorii and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC) and breast cancer. However, due to its toxicity, oral administration can cause various adverse reactions, limiting its clinical application. The aim of this work was to design glycyrrhetinic acid (GA)- and\/or folate (FA)-modified solid lipid nanoparticles (SLNs) for the encapsulation of CTD to target HCC. Four CTD-loaded SLNs (cantharidin solid lipid nanoparticles (CSLNs), glycyrrhetinic acid-modified cantharidin solid lipid nanoparticles (GA-CSLNs), folate-modified cantharidin solid lipid nanoparticles (FA-CSLNs), and glycyrrhetinic acid and folate-modified cantharidin solid lipid nanoparticles (GA-FA-CSLNs)) were prepared by the emulsion ultrasonic dispersion method, and their physicochemical parameters were determined (particle size and distribution, morphology, zeta-potential, entrapment efficiency, drug loading, and hemolysis). Additionally, the antitumor activities of the four SLNs were evaluated comprehensively by tests for cytotoxicity, cell migration, cell cycle, apoptosis, cellular uptake, competition suppression assay, and in vivo tumor suppression assay. Four SLNs showed spherical shapes and mean diameters in the range of 75\u2013110 nm with size dispersion (PDI) within the range of 0.19\u20130.50 and zeta-potential approximately \u201310 mV. The entrapment efficiency of CTD in SLNs was higher than 95% for all tested formulations, and no hemolysis was observed. Compared to GA-CSLNs or CSLNs, GA-FA-CSLNs and FA-CSLNs showed stronger cytotoxicity on hepatocellular carcinoma cells (HepG2), and the cytotoxicity of GA-FA-CSLNs on hepatocyte cells (L-02) was remarkably reduced compared with other formulations. GA-FA-CSLNs and FA-CSLNs also increased the inhibition of HepG2 cell migration, and FA-CSLNs had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells were arrested mainly in the S phase and G2\/M phase. Analysis of competition inhibition experiments showed that GA and FA ligands had targeted effects on HepG2 cells. The in vivo tumor inhibition experiment showed that GA-FA-CSLNs and FA-CSLNs had excellent tumor inhibition ability\u2014their tumor inhibition rates were 96.46% and 89.92%, respectively. Our results indicate that GA-FA-CSLNs and FA-CSLNs have a promising future in the therapeutic intervention of HCC.<\/jats:p>","DOI":"10.3390\/molecules27206786","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T02:10:27Z","timestamp":1665540627000},"page":"6786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Development of Glycyrrhetinic Acid and Folate Modified Cantharidin Loaded Solid Lipid Nanoparticles for Targeting Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"27","author":[{"given":"Yilin","family":"Xu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"},{"name":"The Second Hospital of Hunan University of Chinese Medicine, Changsha 410005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangcheng","family":"Ning","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonglan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41575-019-0229-4","article-title":"Tumour evolution in hepatocellular carcinoma","volume":"17","author":"Craig","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s15010-019-01345-y","article-title":"Epidemiological and etiological variations in hepatocellular carcinoma","volume":"48","author":"Sagnelli","year":"2020","journal-title":"Infection"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Oura, K., Morishita, A., Tani, J., and Masaki, T. (2021). Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115801"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/09553002.2021.1857453","article-title":"Radiofrequency ablation and stereotactic body radiotherapy for hepatocellular carcinoma: Should they clash or reconcile?","volume":"97","author":"Rim","year":"2021","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.31557\/APJCP.2019.20.8.2303","article-title":"Combined Hyperthermia and Radiation Therapy for Treatment of Hepatocellular Carcinoma","volume":"20","author":"Talaat","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"188314","DOI":"10.1016\/j.bbcan.2019.188314","article-title":"Challenges in liver cancer and possible treatment approaches","volume":"1873","author":"Anwanwan","year":"2020","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1007\/s00261-019-01952-1","article-title":"Combination therapy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for small hepatocellular carcinoma: Comparison with TACE or RFA monotherapy","volume":"44","author":"Kim","year":"2019","journal-title":"Abdom. Radiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1080\/02656736.2018.1562571","article-title":"Comparison of microwave ablation and radiofrequency ablation for hepatocellular carcinoma: A systematic review and meta-analysis","volume":"36","author":"Tan","year":"2019","journal-title":"Int. J. Hyperth."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/pin.12895","article-title":"Precision pathology analysis of the development and progression of hepatocellular carcinoma: Implication for precision diagnosis of hepatocellular carcinoma","volume":"70","author":"Ueno","year":"2020","journal-title":"Pathol. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jcis.2021.09.174","article-title":"Magnetic implants in vivo guiding sorafenib liver delivery by superparamagnetic solid lipid nanoparticles","volume":"608","author":"Iacobazzi","year":"2021","journal-title":"J. Colloid Interface Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Alqahtani, A., Khan, Z., Alloghbi, A., Said Ahmed, T.S., Ashraf, M., and Hammouda, D.M. (2019). Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies. Medicina, 55.","DOI":"10.3390\/medicina55090526"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"116012","DOI":"10.1016\/j.bmc.2021.116012","article-title":"Antitumor potential of the protein phosphatase inhibitor, cantharidin, and selected derivatives","volume":"32","author":"Ren","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.canlet.2008.06.029","article-title":"Cantharidin reverses multidrug resistance of human hepatoma HepG2\/ADM cells via down-regulation of P-glycoprotein expression","volume":"272","author":"Zheng","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"108939","DOI":"10.1016\/j.cbi.2020.108939","article-title":"Cantharidin suppresses gastric cancer cell migration\/invasion by inhibiting the PI3K\/Akt signaling pathway via CCAT1","volume":"317","author":"Song","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111285","DOI":"10.1016\/j.colsurfb.2020.111285","article-title":"Enhanced anticancer efficacy of cantharidin by mPEG-PLGA micellar encapsulation: An effective strategy for application of a poisonous traditional Chinese medicine","volume":"196","author":"Yao","year":"2020","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhou, L., Zou, M., Zhu, K., Ning, S., and Xia, X. (2019). Development of 11-DGA-3-O-Gal-Modified Cantharidin Liposomes for Treatment of Hepatocellular Carcinoma. Molecules, 24.","DOI":"10.3390\/molecules24173080"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"590","DOI":"10.3389\/fphar.2019.00590","article-title":"Breaking Glucose Transporter 1\/Pyruvate Kinase M2 Glycolytic Loop Is Required for Cantharidin Inhibition of Metastasis in Highly Metastatic Breast Cancer","volume":"10","author":"Pan","year":"2019","journal-title":"Front Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1111\/1759-7714.13414","article-title":"Cantharidin-loaded functional mesoporous titanium peroxide nanoparticles for non-small cell lung cancer targeted chemotherapy combined with high effective photodynamic therapy","volume":"11","author":"Zheng","year":"2020","journal-title":"Thorac. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Su, C.C., Lee, K.I., Chen, M.K., Kuo, C.Y., Tang, C.H., and Liu, S.H. (2016). Cantharidin Induced Oral Squamous Cell Carcinoma Cell Apoptosis via the JNK-Regulated Mitochondria and Endoplasmic Reticulum Stress-Related Signaling Pathways. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168095"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.7150\/ijbs.51638","article-title":"Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p\/DKK3 axis to inactivate \u03b2-catenin nuclear translocation and LEF1 translation","volume":"17","author":"Hu","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2147\/DDDT.S282777","article-title":"Combination of Sodium Cantharidinate with Cisplatin Synergistically Hampers Growth of Cervical Cancer","volume":"15","author":"Chen","year":"2021","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Naz, F., Wu, Y., Zhang, N., Yang, Z., and Yu, C. (2020). Anticancer Attributes of Cantharidin: Involved Molecular Mechanisms and Pathways. Molecules, 25.","DOI":"10.3390\/molecules25143279"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105033","DOI":"10.1016\/j.fitote.2021.105033","article-title":"Tumor-targeted hyaluronic acid-mPEG modified nanostructured lipid carriers for cantharidin delivery: An in vivo and in vitro study","volume":"155","author":"Sun","year":"2021","journal-title":"Fitoterapia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1002\/jat.4003","article-title":"Cantharidin-induced acute hepatotoxicity: The role of TNF-\u03b1, IKK-\u03b1, Bcl-2, Bax and caspase3","volume":"40","author":"Yu","year":"2020","journal-title":"J. Appl. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1021\/acs.chemrestox.9b00233","article-title":"UPLC-Q-TOF\/MS Based Metabolomics Approach to Study the Hepatotoxicity of Cantharidin on Mice","volume":"32","author":"Zhu","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.2174\/0929867324666170414165253","article-title":"Overview of Cantharidin and its Analogues","volume":"25","author":"Wang","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/13543776.2020.1720649","article-title":"Solid lipid nanoparticles: A review on recent perspectives and patents","volume":"30","author":"Paliwal","year":"2020","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"580118","DOI":"10.3389\/fchem.2021.580118","article-title":"Lipid Nanoparticles as Carriers for Bioactive Delivery","volume":"9","author":"Dhiman","year":"2021","journal-title":"Front. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bay\u00f3n-Cordero, L., Alkorta, I., and Arana, L. (2019). Application of Solid Lipid Nanoparticles to Improve the Efficiency of Anticancer Drugs. Nanomaterials, 9.","DOI":"10.3390\/nano9030474"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2019020396","article-title":"Solid Lipid Nanoparticles: Vital Characteristics and Prospective Applications in Cancer Treatment","volume":"36","author":"Olteanu","year":"2019","journal-title":"Crit. Rev. Ther. Drug Carrier Syst."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115682","DOI":"10.1016\/j.carbpol.2019.115682","article-title":"Targeted delivery and apoptosis induction of trans-resveratrol-ferulic acid loaded chitosan coated folic acid conjugate solid lipid nanoparticles in colon cancer cells","volume":"231","author":"Thangam","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1016\/j.xphs.2020.03.001","article-title":"18-GA-Suc Modified Liposome Loading Cantharidin for Augmenting Hepatic Specificity: Preparation, Characterization, Antitumor Effects, and Liver-Targeting Efficiency","volume":"109","author":"Zhu","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/ddr.21698","article-title":"An outlook on procedures of conjugating folate to (co)polymers and drugs for effective cancer targeting","volume":"81","author":"Kharkar","year":"2020","journal-title":"Drug Dev. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dharmatti, R., Miyatake, H., Nandakumar, A., Ueda, M., Kobayashi, K., Kiga, D., Yamamura, M., and Ito, Y. (2019). Enhancement of Binding Affinity of Folate to Its Receptor by Peptide Conjugation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092152"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1021\/acs.bioconjchem.8b00428","article-title":"Lactobionic\/Folate Dual-Targeted Amphiphilic Maltodextrin-Based Micelles for Targeted Codelivery of Sulfasalazine and Resveratrol to Hepatocellular Carcinoma","volume":"29","author":"Anwar","year":"2018","journal-title":"Bioconjug. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.actbio.2017.06.017","article-title":"Folate-targeted polymersomes loaded with both paclitaxel and doxorubicin for the combination chemotherapy of hepatocellular carcinoma","volume":"58","author":"Zhu","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s10856-017-5930-7","article-title":"Hybrid polymeric-protein nano-carriers (HPPNC) for targeted delivery of TGF\u03b2 inhibitors to hepatocellular carcinoma cells","volume":"28","author":"Hanafy","year":"2017","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12951-020-00677-4","article-title":"Synergistic co-delivery of diacid metabolite of norcantharidin and ABT-737 based on folate-modified lipid bilayer-coated mesoporous silica nanoparticle against hepatic carcinoma","volume":"18","author":"Liu","year":"2020","journal-title":"J. Nanobiotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8581","DOI":"10.3390\/ijerph110808581","article-title":"Influence of surfactant and lipid type on the physicochemical properties and biocompatibility of solid lipid nanoparticles","volume":"11","author":"Pizzol","year":"2014","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1080\/03639045.2018.1492606","article-title":"Amphotericin B-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carrier (NLCs): Effect of drug loading and biopharmaceutical characterizations","volume":"44","author":"Jansook","year":"2018","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_42","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_43","unstructured":"National Pharmacopoeia Committee (2020). Chinese Pharmacopoeia, Part IV (2020 Edition) [S]."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"118810","DOI":"10.1016\/j.carbpol.2021.118810","article-title":"Hydrazided hyaluronan\/cisplatin\/indocyanine green coordination nanoprodrug for photodynamic chemotherapy in liver cancer","volume":"276","author":"Hou","year":"2022","journal-title":"Carbohydr. Polym."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/20\/6786\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:49:50Z","timestamp":1760143790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/20\/6786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,11]]},"references-count":44,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27206786"],"URL":"https:\/\/doi.org\/10.3390\/molecules27206786","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,11]]}}}