{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:20:59Z","timestamp":1769599259844,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDB\/00100\/2020"],"award-info":[{"award-number":["UIDB\/00100\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["LA\/P\/0056\/2020"],"award-info":[{"award-number":["LA\/P\/0056\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["PTDC\/QUI-QIN\/28662\/2017"],"award-info":[{"award-number":["PTDC\/QUI-QIN\/28662\/2017"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["SFRH\/BD\/100515\/2014"],"award-info":[{"award-number":["SFRH\/BD\/100515\/2014"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["SFRH\/BD\/139271\/2018"],"award-info":[{"award-number":["SFRH\/BD\/139271\/2018"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["SFRH\/BD\/139412\/2018"],"award-info":[{"award-number":["SFRH\/BD\/139412\/2018"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["CEEC-IND 2017"],"award-info":[{"award-number":["CEEC-IND 2017"]}]},{"name":"European Social Fund","award":["UIDB\/00100\/2020"],"award-info":[{"award-number":["UIDB\/00100\/2020"]}]},{"name":"European Social Fund","award":["LA\/P\/0056\/2020"],"award-info":[{"award-number":["LA\/P\/0056\/2020"]}]},{"name":"European Social Fund","award":["PTDC\/QUI-QIN\/28662\/2017"],"award-info":[{"award-number":["PTDC\/QUI-QIN\/28662\/2017"]}]},{"name":"European Social Fund","award":["SFRH\/BD\/100515\/2014"],"award-info":[{"award-number":["SFRH\/BD\/100515\/2014"]}]},{"name":"European Social Fund","award":["SFRH\/BD\/139271\/2018"],"award-info":[{"award-number":["SFRH\/BD\/139271\/2018"]}]},{"name":"European Social Fund","award":["SFRH\/BD\/139412\/2018"],"award-info":[{"award-number":["SFRH\/BD\/139412\/2018"]}]},{"name":"European Social Fund","award":["CEEC-IND 2017"],"award-info":[{"award-number":["CEEC-IND 2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive targeting, using biotin and polylactide (PLA), respectively. All compounds with the general formula, [Ru(\u03b75-CpR)(P)(2,2\u2032-bipy-4,4\u2032-PLA-biotin)][CF3SO3], where R is -H or -CH3 and P is P(C6H5)3, P(C6H4F)3 or P(C6H4OCH3)3, were tested against triple-negative breast cancer cells MDA-MB-231 showing IC50 values between 2.3\u201314.6 \u00b5M, much better than cisplatin, a classical chemotherapeutic drug, in the same experimental conditions. We selected compound 1 (where R is H and P is P(C6H5)3), for further studies as it was the one showing the best biological effect. In a competitive assay with biotin, we showed that cell uptake via SMVT receptors seems to be the main transport route into the cells for this compound, validating the strategy of including biotin in the design of the compound. The effects of the compound on the hallmarks of cancer show that the compound leads to apoptosis, interferes with proliferation by affecting the formation of cell colonies in a dose-dependent manner and disrupts the cell cytoskeleton. Preliminary in vivo assays in N: NIH(S)II-nu\/nu mice show that the concentrations of compound 1 used in this experiment (maximum 4 mg\/kg) are safe to use in vivo, although some signs of liver toxicity are already found. In addition, the new compound shows a tendency to control tumor growth, although not significantly. In sum, we showed that compound 1 shows promising anti-cancer effects, bringing a new avenue for triple-negative breast cancer therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics14071388","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T01:40:36Z","timestamp":1656639636000},"page":"1388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Biotinylated Polymer-Ruthenium Conjugates: In Vitro and In Vivo Studies in a Triple-Negative Breast Cancer Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4974-1075","authenticated-orcid":false,"given":"Leonor","family":"C\u00f4rte-Real","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences and Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-4623","authenticated-orcid":false,"given":"Ana Rita","family":"Br\u00e1s","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences and Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio-Sustainability, University of Minho, Campus de Gualtar, Edif\u00edcio 18, 4710-057 Braga, Portugal"}]},{"given":"Adhan","family":"Pilon","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences and Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-2277","authenticated-orcid":false,"given":"Nuno","family":"Mendes","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-9233","authenticated-orcid":false,"given":"Ana Sofia","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Tiago D.","family":"Martins","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences and Department of Chemical Engineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-5031","authenticated-orcid":false,"given":"Jos\u00e9 Paulo S.","family":"Farinha","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences and Department of Chemical Engineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3068-4920","authenticated-orcid":false,"given":"M. Concei\u00e7\u00e3o","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences and Department of Chemical Engineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-0086","authenticated-orcid":false,"given":"F\u00e1tima","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-2218","authenticated-orcid":false,"given":"M. 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(2021). Challenges towards targeted drug delivery in cancer nanomedicines. Processes, 9.","DOI":"10.3390\/pr9091527"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fmolb.2020.00193","article-title":"Nanoparticle-based drug delivery in cancer therapy and its role in overcoming drug resistance","volume":"7","author":"Yao","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/s41467-018-03705-y","article-title":"Progress and challenges towards targeted delivery of cancer therapeutics","volume":"9","author":"Rosenblum","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41392-017-0004-3","article-title":"Controlled drug delivery vehicles for cancer treatment and their performance","volume":"3","author":"Senapati","year":"2018","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_5","first-page":"1","article-title":"A Review on drug delivery system for tumor therapy","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3390\/10010114","article-title":"Covalent polymer-drug conjugates","volume":"10","author":"Elvira","year":"2005","journal-title":"Molecules"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1517\/17425240903158917","article-title":"Biodegradable amphiphilic polymer\u2013drug conjugate micelles","volume":"6","author":"Hu","year":"2009","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_8","first-page":"158","article-title":"Polymer-drug conjugates: Novel carriers for cancer chemotherapy","volume":"58","author":"Seifu","year":"2019","journal-title":"Polym. Technol. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1080\/00914037.2019.1655745","article-title":"Polymer-drug conjugates as nanomedicine: A review","volume":"69","author":"Girase","year":"2020","journal-title":"Int. J. Polym. Mater. Polym. Biomater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1021\/cm2031569","article-title":"Polymeric conjugates for drug delivery","volume":"24","author":"Larson","year":"2012","journal-title":"Chem. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.nano.2010.05.005","article-title":"Advances in polymeric micelles for drug delivery and tumor targeting","volume":"6","author":"Kedar","year":"2010","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0168-3659(99)00248-5","article-title":"Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review","volume":"65","author":"Maeda","year":"2000","journal-title":"J. Control. Release"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12320","DOI":"10.1002\/anie.201403036","article-title":"Engineered Nanoparticles for Drug Delivery in Cancer Therapy","volume":"53","author":"Sun","year":"2014","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1021\/ma402078d","article-title":"Superior chemotherapeutic benefits from the ruthenium-based anti-metastatic drug NAMI-A through conjugation to polymeric micelles","volume":"47","author":"Blunden","year":"2014","journal-title":"Macromolecules"},{"key":"ref_15","first-page":"1","article-title":"A Versatile Polymer Micelle Drug Delivery System for Encapsulation and InVivo Stabilization of Hydrophobic Anticancer Drugs","volume":"2012","author":"Carie","year":"2012","journal-title":"J. Drug Deliv."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hussein, Y.H.A., and Youssry, M. (2018). Polymeric micelles of biodegradable diblock copolymers: Enhanced encapsulation of hydrophobic drugs. Materials, 11.","DOI":"10.3390\/ma11050688"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"613","DOI":"10.4155\/tde-2020-0008","article-title":"Polymeric micelles for anticancer drug delivery","volume":"11","author":"Majumder","year":"2020","journal-title":"Ther. Deliv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.jconrel.2014.06.042","article-title":"Progress of drug-loaded polymeric micelles into clinical studies","volume":"190","author":"Cabral","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1208\/s12249-014-0139-2","article-title":"Encapsulation in nanoparticles improves anti-cancer efficacy of carboplatin","volume":"15","author":"Sadhukha","year":"2014","journal-title":"AAPS Pharmscitech"},{"key":"ref_20","first-page":"54","article-title":"Nanoparticles in biomedical applications","volume":"2","author":"McNamara","year":"2017","journal-title":"Adv. Phys. X"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s11671-021-03628-6","article-title":"Nanoparticles for Cancer Therapy: Current Progress and Challenges","volume":"16","author":"Gavas","year":"2021","journal-title":"Nanoscale Res. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s11671-021-03489-z","article-title":"Nanoparticles: A new approach to upgrade cancer diagnosis and treatment","volume":"16","author":"Yu","year":"2021","journal-title":"Nanoscale Res. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9135","DOI":"10.1021\/acs.inorgchem.9b00735","article-title":"Ruthenium\u2013Cyclopentadienyl Bipyridine\u2013Biotin Based Compounds: Synthesis and Biological Effect","volume":"58","author":"Karas","year":"2019","journal-title":"Inorg. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"975","DOI":"10.2147\/IJN.S68861","article-title":"Liposomes as nanomedical devices","volume":"10","author":"Bozzuto","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.addr.2012.09.037","article-title":"Liposomal drug delivery systems: From concept to clinical applications","volume":"65","author":"Allen","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fphar.2015.00286","article-title":"Advances and challenges of liposome assisted drug delivery","volume":"6","author":"Sercombe","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kim, M.W., Kwon, S.H., Choi, J.H., and Lee, A. (2018). A promising biocompatible platform: Lipid-based and bio-inspired smart drug delivery systems for cancer therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123859"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1016\/j.matt.2019.09.016","article-title":"Drug-polymer hybrid macromolecular engineering: Degradable PEG integrated by platinum (IV) for cancer therapy","volume":"1","author":"Qian","year":"2019","journal-title":"Matter"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6600","DOI":"10.1039\/C4PY00802B","article-title":"Enhanced drug toxicity by conjugation of platinum drugs to polymers with guanidine containing zwitterionic functional groups that mimic cell-penetrating peptides","volume":"5","author":"Karim","year":"2014","journal-title":"Polym. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s10904-019-01325-7","article-title":"Polyamidoamine-drug conjugates containing metal-based anticancer compounds","volume":"30","author":"Aderibigbe","year":"2020","journal-title":"J. Inorg. Organomet. Polym. Mater."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Uivarosi, V., Olar, R., and Badea, M. (2017). Nanoformulation as a tool for improve the pharmacological profile of platinum and ruthenium anticancer drugs. Descriptive Inorganic Chemistry Researches of Metal Compounds, IntechOpen. Chapter 1.","DOI":"10.5772\/intechopen.68306"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Alven, S., Nqoro, X., Buyana, B., and Aderibigbe, B.A. (2020). Polymer-drug conjugate, a potential therapeutic to combat breast and lung cancer. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12050406"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1021\/bm4013919","article-title":"Enhanced delivery of the RAPTA-C macromolecular chemotherapeutic by conjugation to degradable polymeric micelles","volume":"14","author":"Blunden","year":"2013","journal-title":"Biomacromolecules"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mabi.201600513","article-title":"Enhanced Antimetastatic Activity of the Ruthenium Anticancer Drug RAPTA-C Delivered in Fructose-Coated Micelles","volume":"17","author":"Lu","year":"2017","journal-title":"Macromol. Biosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1603702","DOI":"10.1002\/adma.201603702","article-title":"An Amphiphilic Ruthenium Polymetallodrug for Combined Photodynamic Therapy and Photochemotherapy In Vivo","volume":"29","author":"Sun","year":"2017","journal-title":"Adv. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.eurpolymj.2019.01.074","article-title":"Brush-shaped RAFT polymer micelles as nanocarriers for a ruthenium (II) complex photodynamic anticancer drug","volume":"113","author":"Wang","year":"2019","journal-title":"Eur. Polym. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1039\/C9SC05976H","article-title":"Ruthenium-initiated polymerization of lactide: A route to remarkable cellular uptake for photodynamic therapy of cancer","volume":"11","author":"Soliman","year":"2020","journal-title":"Chem. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"54433","DOI":"10.1021\/acsami.0c16119","article-title":"Polymeric encapsulation of a ruthenium polypyridine complex for tumor targeted one-and two-photon photodynamic therapy","volume":"12","author":"Karges","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.ejmech.2019.02.061","article-title":"Polymer \u201cruthenium-cyclopentadienyl\u201d conjugates-New emerging anti-cancer drugs","volume":"168","author":"Moreira","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jinorgbio.2013.07.002","article-title":"First polymer \u201cruthenium-cyclopentadienyl\u201d complex as potential anticancer agent","volume":"127","author":"Valente","year":"2013","journal-title":"J. Inorg. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jinorgbio.2010.10.009","article-title":"DNA interaction and cytotoxicity studies of new ruthenium (II) cyclopentadienyl derivative complexes containing heteroaromatic ligands","volume":"105","author":"Moreno","year":"2011","journal-title":"J. Inorg. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jinorgbio.2012.06.016","article-title":"[RuII (\u03b75-C5H5)(bipy)(PPh3)]+, a promising large spectrum antitumor agent: Cytotoxic activity and interaction with human serum albumin","volume":"117","author":"Isabel","year":"2012","journal-title":"J. Inorg. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.addr.2016.06.018","article-title":"Polylactic acid (PLA) controlled delivery carriers for biomedical applications","volume":"107","author":"Tyler","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.ejmech.2018.12.022","article-title":"Unprecedented inhibition of P-gp activity by a novel ruthenium-cyclopentadienyl compound bearing a bipyridine-biotin ligand","volume":"163","author":"Karas","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/toxsci\/kfab041","article-title":"Anti-cancer activity and in vitro to in vivo mechanistic recapitulation of novel ruthenium-based metallodrugs in the zebrafish model","volume":"182","author":"Karas","year":"2021","journal-title":"Toxicol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1071\/CH9771601","article-title":"Cyclopentadienyl-ruthenium and-osmium chemistry. IV. Convenient high-yield synthesis of some cyclopentadienyl ruthenium or osmium tertiary phosphine halide complexes","volume":"30","author":"Bruce","year":"1977","journal-title":"Aust. J. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ejmech.2017.11.059","article-title":"Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cells","volume":"143","author":"Teixeira","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1021\/ed100461v","article-title":"Polymer molecular weight analysis by 1H NMR spectroscopy","volume":"88","author":"Izunobi","year":"2011","journal-title":"J. Chem. Educ."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1017\/S143192761300175X","article-title":"Cellular uptake mechanisms of an antitumor ruthenium compound: The endosomal\/lysosomal system as a target for anticancer metal-based drugs","volume":"19","author":"Matos","year":"2013","journal-title":"Microsc. Microanal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1002\/marc.200350031","article-title":"Characterization of defined metal-containing supramolecular block copolymers","volume":"24","author":"Meier","year":"2003","journal-title":"Macromol. Rapid Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4629","DOI":"10.1021\/acs.inorgchem.8b00358","article-title":"Methyl-cyclopentadienyl ruthenium compounds with 2, 2\u2032-bipyridine derivatives display strong anticancer activity and multidrug resistance potential","volume":"57","author":"Teixeira","year":"2018","journal-title":"Inorg. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10403","DOI":"10.1039\/C5CC03075G","article-title":"Recent development of biotin conjugation in biological imaging, sensing, and target delivery","volume":"51","author":"Ren","year":"2015","journal-title":"Chem. Commun."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/7\/1388\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:41:19Z","timestamp":1760139679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/7\/1388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["pharmaceutics14071388"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14071388","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]}}}