{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:16:32Z","timestamp":1789384592376,"version":"build-2803163510"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State University of New York Network of Excellence","award":["1-114-594"],"award-info":[{"award-number":["1-114-594"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The interactions of chemotherapeutic drugs with nanocage protein apoferritin (APO) are the key features in the effective encapsulation and release of highly toxic drugs in APO-based controlled drug delivery systems. The encapsulation enables mitigating the drugs\u2019 side effects, collateral damage to healthy cells, and adverse immune reactions. Herein, the interactions of anthracycline drugs with APO were studied to assess the effect of drug lipophilicity on their encapsulation excess n and in vitro activity. Anthracycline drugs, including doxorubicin (DOX), epirubicin (EPI), daunorubicin (DAU), and idarubicin (IDA), with lipophilicity P from 0.8 to 15, were investigated. We have found that in addition to hydrogen-bonded supramolecular ensemble formation with n = 24, there are two other competing contributions that enable increasing n under strong polar interactions (APO(DOX)) or under strong hydrophobic interactions (APO(IDA) of the highest efficacy). The encapsulation\/release processes were investigated using UV-Vis, fluorescence, circular dichroism, and FTIR spectroscopies. The in vitro cytotoxicity\/growth inhibition tests and flow cytometry corroborate high apoptotic activity of APO(drugs) against targeted MDA-MB-231 adenocarcinoma and HeLa cells, and low activity against healthy MCF10A cells, demonstrating targeting ability of nanodrugs. A model for molecular interactions between anthracyclines and APO nanocarriers was developed, and the relationships derived compared with experimental results.<\/jats:p>","DOI":"10.3390\/ijms22031362","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T09:25:22Z","timestamp":1611912322000},"page":"1362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cancer-Targeted Controlled Delivery of Chemotherapeutic Anthracycline Derivatives Using Apoferritin Nanocage Carriers"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-3468","authenticated-orcid":false,"given":"Katarzyna","family":"Kurz\u0105tkowska","sequence":"first","affiliation":[{"name":"Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA"},{"name":"Department of Biosensors, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10 Str., 10-748 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Manuel A.","family":"Pazos","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cancer Research Center, University at Albany, State University of New York, Rensselaer, NY 12222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason I.","family":"Herschkowitz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cancer Research Center, University at Albany, State University of New York, Rensselaer, NY 12222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8127-8260","authenticated-orcid":false,"given":"Maria","family":"Hepel","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nnano.2007.387","article-title":"Nanocarriers as an emerging platform for cancer therapy","volume":"2","author":"Peer","year":"2007","journal-title":"Nat. Nanotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1021\/cr5004634","article-title":"Mechanisms of drug release in nanotherapeutic delivery systems","volume":"115","author":"Wong","year":"2015","journal-title":"Chem Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrc.2016.108","article-title":"Cancer nanomedicine: Progress, challenges and opportunities","volume":"17","author":"Shi","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.bios.2017.01.049","article-title":"Plasmonic nanocarrier grid-enhanced Raman sensor for studies of anticancer drug delivery","volume":"91","author":"Kurzatkowska","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10698","DOI":"10.1021\/acs.analchem.5b03456","article-title":"Surface enhanced Raman scattering detection of cancer biomarkers with bifunctional nanocomposite probe","volume":"87","author":"Li","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.drup.2015.08.004","article-title":"Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach","volume":"23","author":"Taylor","year":"2015","journal-title":"Drug Resist. Updat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.drup.2017.05.002","article-title":"Targeted nanomedicine for cancer therapeutics: Towards precision medicine overcoming drug resistance","volume":"31","author":"Livney","year":"2017","journal-title":"Drug Resist. Updat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1046\/j.1432-1327.2000.01030.x","article-title":"The relative importance of passive and P-glycoprotein mediated anthracycline efflux form multidrug-resistant cells","volume":"267","author":"Wielinga","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jconrel.2017.09.015","article-title":"Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles","volume":"267","author":"Yhee","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6878","DOI":"10.1038\/srep06878","article-title":"Glycol chitosan nanoparticles as specialized cancer therapeutic vehicles: Sequential delivery of doxorubicin and Bcl-2 siRNA","volume":"4","author":"Yoon","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Grel, H., Ratajczak, K., Jakiela, S., and Stobiecka, M. (2020). Gated Resonance Energy Transfer (gRET) Controlled by Programmed Death Protein Ligand 1. Nanomaterials, 10.","DOI":"10.3390\/nano10081592"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.bios.2016.01.068","article-title":"Nanostructured SERS-electrochemical biosensors for testing of anticancer drug interactions with DNA","volume":"80","author":"Ilkhani","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/1061186X.2011.611518","article-title":"Recent advances in ligand targeted therapy","volume":"20","author":"Trapani","year":"2012","journal-title":"J. Drug Targeting"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1002\/med.21387","article-title":"Small Molecules for Active Targeting in Cancer","volume":"36","author":"Kue","year":"2016","journal-title":"Med. Res. Reviews"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1002\/adhm.201500226","article-title":"H-Chain Ferritin: A Natural Nuclei Targeting and Bioactive Delivery Nanovector","volume":"4","author":"Zhang","year":"2015","journal-title":"Adv. Healthcare Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7763","DOI":"10.2147\/IJN.S149306","article-title":"Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine","volume":"12","author":"Santiago","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"30780","DOI":"10.1039\/C4RA05270F","article-title":"Nanocarriers with dual pH-sensitivity for enhanced tumor cell uptake and rapid intracellular drug release","volume":"4","author":"Wu","year":"2014","journal-title":"RSC Adv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14900","DOI":"10.1073\/pnas.1407808111","article-title":"H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection","volume":"111","author":"Liang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1073\/pnas.0913192107","article-title":"Binding and uptake of H-ferritin are mediated by human transferrin receptor-1","volume":"107","author":"Li","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"125","DOI":"10.13171\/mjc64\/01706081223-hepel","article-title":"Controlled release of targeted anti-leukemia drugs azacitidine and decitabine monitored using surface-enhanced Raman scattering (SERS) spectroscopy","volume":"6","author":"Smith","year":"2017","journal-title":"Mediterr. J. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.13171\/mjc71\/01803171500-hepel","article-title":"Controlled release of targeted chemotherapeutic drug dabrafenib for melanoma cancers monitored using surface-enhanced Raman scattering (SERS) spectroscopy","volume":"7","author":"Running","year":"2018","journal-title":"Mediterr. J. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Matijevic, E. (2012). Detection of Oxidative Stress Biomarkers Using Functional Gold Nanoparticles. Fine Particles in Medicine and Pharmacy, Springer Sci Publ.","DOI":"10.1007\/978-1-4614-0379-1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1016\/j.biomaterials.2010.12.064","article-title":"Double-shell gold nanoparticle-based DNA-carriers with poly-L-lysine binding surface","volume":"32","author":"Stobiecka","year":"2011","journal-title":"Biomaterials"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Serra, P.A. (2011). Detection of Oxidative Stress Biomarkers Using Novel Nanostructured Biosensors. New Perspectives in Biosensors Technology and Applications, INTECH.","DOI":"10.5772\/936"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrfmmm.2012.05.005","article-title":"Intervention of glutathione in pre-mutagenic catechol-mediated DNA damage in the presence of copper(II) ions","volume":"735","author":"Hepel","year":"2012","journal-title":"Mutat. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jphotochem.2011.09.028","article-title":"Comparative kinetic model of fluorescence enhancement in selective binding of monochlorobimane to glutathione","volume":"225","author":"Hepel","year":"2011","journal-title":"J. Photochem. Photobiol. A"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.saa.2017.11.017","article-title":"Supramolecular Interactions of Oxidative Stress Biomarker Glutathione with Fluorone Black","volume":"192","author":"Hepel","year":"2018","journal-title":"Spectrochim. Acta A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.phrs.2016.03.002","article-title":"Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer","volume":"107","author":"Truffi","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3453","DOI":"10.1039\/b705326f","article-title":"Encapsulation of platinum anticancer drugs by apoferritin","volume":"33","author":"Yang","year":"2007","journal-title":"Chem. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1166\/jbn.2012.1406","article-title":"A novel protein-based anticancer drug encapsulating nonosphere: Apoferritin-doxorubicin complex","volume":"8","author":"Kilic","year":"2012","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.it.2007.07.011","article-title":"Immunogenicity of protein, therapeutics","volume":"28","author":"Groot","year":"2007","journal-title":"Trends Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1080\/17425247.2016.1224848","article-title":"Apoferritin nanocage as drug reservoir: Is it a reliable drug delivery system?","volume":"13","author":"Tosi","year":"2016","journal-title":"Expert Opin. Drug Delivery"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.nbt.2014.12.006","article-title":"Ferritin family proteins and their use in bionanotechnology","volume":"32","author":"He","year":"2015","journal-title":"New Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1080\/17425247.2017.1243528","article-title":"Protein cage nanostructure as drug delivery system: Magnifying glass in appoferritin","volume":"14","author":"Balletti","year":"2017","journal-title":"Expert Opin. Drug Delivery"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6899","DOI":"10.1007\/s00216-019-02061-0","article-title":"Monitoring of dynamic ATP level changes by oligomycin-modulated ATP synthase inhibition in SW480 cancer cells using fluorescent \u201cOn-Off\u201d switching DNA aptamer","volume":"411","author":"Ratajczak","year":"2019","journal-title":"Analytical and Bioanalytical Chemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nano.2019.04.001","article-title":"Ferritin-based anticancer metallodrug delivery: Crystallographic, analytical and cytotoxicity studies","volume":"20","author":"Monti","year":"2019","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.jinorgbio.2009.05.001","article-title":"Characterization and cellular uptake of platinum anticancer drugs encapsulated in apoferritin","volume":"103","author":"Xing","year":"2009","journal-title":"J. Inorg. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1039\/C5CC10365G","article-title":"Cisplatin encapsulation within a ferritin nanocage: A high-resolution crystallographic study","volume":"52","author":"Pontillo","year":"2016","journal-title":"Chem. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12278","DOI":"10.1039\/c3nr04268e","article-title":"Anti-body conjugates: Targeting melanoma with cisplatin encapsulated in protein-cage nanoparticles based on human ferritin","volume":"5","author":"Falvo","year":"2013","journal-title":"Nanoscale"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ijpharm.2016.12.038","article-title":"Apoferritin nanocage as streptomycin drug reservoir: Technological optimization of a new drug delivery system","volume":"518","author":"Ruozi","year":"2017","journal-title":"Int. J. Pharmac."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1039\/C3TB20081G","article-title":"Bio-inspired protein-gold nanoconstruct with core-void-shell structure: Beyond a chemo drug carrier","volume":"1","author":"Liu","year":"2013","journal-title":"J. Mater. Chem. B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8700","DOI":"10.1039\/c0jm04321d","article-title":"Apoferritin-based nanomedicine platform for drug delivery: Equilibrium binding study of daunomycin with DNA","volume":"21","author":"Wu","year":"2011","journal-title":"J. Mater. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14430","DOI":"10.1021\/acsami.6b04286","article-title":"Site-direct conjugation of antibodies to apoferritin nanocarrier for targeted drug delivery to prostate cancer cells","volume":"8","author":"Dostalova","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.2147\/IJN.S130267","article-title":"Apoferritin as ubiquitous nanocarrier with excellent shelf life","volume":"12","author":"Dostalova","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1021\/acs.molpharmaceut.7b00341","article-title":"Apoferritin nanocage for brain targeted doxorubicin delivery","volume":"14","author":"Chen","year":"2017","journal-title":"Mol. Pharmaceutis"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1021\/acs.biomac.7b01545","article-title":"Extending half-life of H-ferritin nanoparticles by fusing albumin binding domain for doxorubicin encapsulation","volume":"19","author":"Wang","year":"2018","journal-title":"Biomacromolecules"},{"key":"ref_47","first-page":"5847","article-title":"Develoopment and characterization of folic acid-functionalized apoferritin as a delivery vehicle for epirubicin against MCF-7 breasr cancer cells","volume":"46","author":"Alqaraghuli","year":"2018","journal-title":"Art. Cells Nanomed. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/j.1751-1097.2009.00696.x","article-title":"Cellular uptake and photodynamic activity of protein nanocages containing methylene blue photosensitizing drug","volume":"86","author":"Yan","year":"2010","journal-title":"Photochem. Photobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1021\/mp3006177","article-title":"Curcumin\/Gd loaded apoferritin: A novel \u201ctheranostic\u201d agent to prevent hepatocellular damage in toxic induced acute hepatitis","volume":"10","author":"Cutrin","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/CAD.0000000000000182","article-title":"Emerging delivery systems to reduce doxorubicin cardiotoxicity and improve therapeutic index: Focus on liposomes","volume":"26","author":"Tahover","year":"2015","journal-title":"Anti-Cancer Drugs"},{"key":"ref_51","unstructured":"Hepel, M., and Stobiecka, M. (2010). Interactions of Herbicide Atrazine with DNA, Nova Science Publishers."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1124\/pr.56.2.6","article-title":"Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity","volume":"56","author":"Minotti","year":"2014","journal-title":"Pharmacol Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1161\/CIRCULATIONAHA.114.013777","article-title":"Early Detection of Anthracycline Cardiotoxicity and Improvement with Heart Failure Therapy","volume":"131","author":"Cardinale","year":"2015","journal-title":"Circulation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1021\/acs.biomac.8b00012","article-title":"A self-targeting dual ROS\/pH-responsive apoferritin nanocages for spatiotemporally controlled drug delivery to breast cancer","volume":"19","author":"Du","year":"2018","journal-title":"Biomacromolecules"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6575","DOI":"10.2147\/IJN.S211844","article-title":"Targeting cell cycle protein in gastric cancer with CDC20siRNA and anticancer drugs (doxorubicin and quercetin) co-loaded cationic PEGylated nanoniosomes","volume":"14","author":"Hemati","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.msec.2018.10.060","article-title":"Apoferritin nanocages with Au nanoshell coating as drug carrier for multistimuli-responsive drug release","volume":"95","author":"Li","year":"2019","journal-title":"Mater. Sci. Engng. C"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature12327","article-title":"Structural basis for molecular recognition of folic acid by folate receptors","volume":"500","author":"Chen","year":"2013","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1166\/jnn.2016.10700","article-title":"Investigating the fluorescence quenching of doxorubicin in folic acid solutions and its relation to ligand-targeted nanocarriers","volume":"16","author":"Husseini","year":"2016","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16680","DOI":"10.1021\/ja207463b","article-title":"Cell-Specific, Activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy","volume":"133","author":"Santra","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/nsb1096-842","article-title":"Experimentally determined hydrophobicity scale for proteins at membrane interfaces","volume":"3","author":"Wimley","year":"1996","journal-title":"Nat. Struct. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0021-9258(18)56191-3","article-title":"Chemical properties of ferritin and their relation to its vasodepressor activity","volume":"187","author":"Mazur","year":"1950","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/oxfordjournals.jbchem.a126467","article-title":"Studies on ferritin","volume":"41","author":"Nakamura","year":"1954","journal-title":"J. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.jinorgbio.2003.12.015","article-title":"Iron(III) complexation of Desferrioxamine B encapsulated in apoferritin","volume":"98","year":"2004","journal-title":"J. Inorg. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1362\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:17:18Z","timestamp":1760159838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,29]]},"references-count":63,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22031362"],"URL":"https:\/\/doi.org\/10.3390\/ijms22031362","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202012.0513.v1","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,29]]}}}