{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T22:11:33Z","timestamp":1761948693034,"version":"build-2065373602"},"reference-count":81,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NORTE-01-0145-FEDER-000040"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000040"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Marine organisms are able to produce a plethora of small molecules with novel chemical structures and potent biological properties, being a fertile source for discovery of pharmacologically active compounds, already with several marine-derived agents approved as drugs. Glioma is classified by the WHO as the most common and aggressive form of tumor on CNS. Currently, Temozolomide is the only chemotherapeutic option approved by the FDA even though having some limitations. This review presents, for the first time, a comprehensive overview of marine compounds described as anti-glioma agents in the last decade. Nearly fifty compounds were compiled in this document and organized accordingly to their marine sources. Highlights on the mechanism of action and ADME properties were included. Some of these marine compounds could be promising leads for the discovery of new therapeutic alternatives for glioma treatment.<\/jats:p>","DOI":"10.3390\/molecules26092707","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T22:51:42Z","timestamp":1620255102000},"page":"2707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Small Molecules of Marine Origin as Potential Anti-Glioma Agents"],"prefix":"10.3390","volume":"26","author":[{"given":"Ana","family":"Alves","sequence":"first","affiliation":[{"name":"UCIBIO, REQUIMTE, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Laboratory of Pharmaceutical Technology, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-3398","authenticated-orcid":false,"given":"Paulo","family":"Costa","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Laboratory of Pharmaceutical Technology, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4676-1409","authenticated-orcid":false,"given":"Madalena","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Center of Marine and Environmental Research (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es Avenida General Norton de Matos P, 4450-208 Matosinhos, Portugal"}]},{"given":"Domingos","family":"Ferreira","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Laboratory of Pharmaceutical Technology, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4150-8532","authenticated-orcid":false,"given":"Marta","family":"Correia-da-Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Center of Marine and Environmental Research (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es Avenida General Norton de Matos P, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2020, October 18). Cancer. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11622","DOI":"10.1038\/s41598-020-68011-4","article-title":"Longer-term (\u22652 years) survival in patients with glioblastoma in population-based studies pre- and post-2005: A systematic review and meta-analysis","volume":"10","author":"Poon","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_4","first-page":"3","article-title":"Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment","volume":"18","author":"Hanif","year":"2017","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1021\/acschembio.8b00864","article-title":"Tunable Stability of Imidazotetrazines Leads to a Potent Compound for Glioblastoma","volume":"13","author":"Svec","year":"2018","journal-title":"ACS Chem. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.ejpb.2013.08.011","article-title":"Brain targeting effect of camptothecin-loaded solid lipid nanoparticles in rat after intravenous administration","volume":"85","author":"Martins","year":"2013","journal-title":"Eur. J. Pharm. Biopharm. Off. J. Arbeitsgem. Pharm. Verfahrenstech. e.V."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/s12967-017-1303-8","article-title":"Impact of mesenchymal stem cells\u2019 secretome on glioblastoma pathophysiology","volume":"15","author":"Gomes","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.7150\/thno.25025","article-title":"WNT6 is a novel oncogenic prognostic biomarker in human glioblastoma","volume":"8","author":"Goncalves","year":"2018","journal-title":"Theranostics"},{"key":"ref_9","first-page":"221","article-title":"Advances and challenges in the treatment of glioblastoma: A clinician\u2019s perspective","volume":"15","author":"Mrugala","year":"2013","journal-title":"Discov. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1021\/nn203749v","article-title":"Two-order targeted brain tumor imaging by using an optical\/paramagnetic nanoprobe across the blood brain barrier","volume":"6","author":"Yan","year":"2012","journal-title":"ACS Nano"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1634\/theoncologist.11-2-152","article-title":"Therapeutic advances in the treatment of glioblastoma: Rationale and potential role of targeted agents","volume":"11","author":"Reardon","year":"2006","journal-title":"Oncologist"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"797","DOI":"10.3390\/ph7070797","article-title":"The medicinal chemistry of imidazotetrazine prodrugs","volume":"7","author":"Moody","year":"2014","journal-title":"Pharmaceuticals"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ijrobp.2010.04.033","article-title":"Effectiveness of radiotherapy for elderly patients with glioblastoma","volume":"81","author":"Scott","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_14","first-page":"894","article-title":"Radiotherapy and radiosensitizers in the treatment of glioblastoma multiforme","volume":"5","author":"Chang","year":"2007","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ejmech.2019.03.048","article-title":"Targeting gliomas with triazene-based hybrids: Structure-activity relationship, mechanistic study and stability","volume":"172","author":"Braga","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","first-page":"235","article-title":"Computer-aided design of temozolomide derivatives based on alkylglycerone phosphate synthase structure with isothiocyanate and their pharmacokinetic\/toxicity prediction and anti-tumor activity in vitro","volume":"8","author":"Yang","year":"2018","journal-title":"Biomed. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yang, Z., Wei, D., Dai, X., Stevens, M.F.G., Bradshaw, T.D., Luo, Y., and Zhang, J. (2019). C8-Substituted Imidazotetrazine Analogs Overcome Temozolomide Resistance by Inducing DNA Adducts and DNA Damage. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00485"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejmech.2018.12.033","article-title":"Recent advances in the discovery of small molecules targeting glioblastoma","volume":"164","author":"Fernandes","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/nm.3328","article-title":"Coordinate activation of Shh and PI3K signaling in PTEN-deficient glioblastoma: New therapeutic opportunities","volume":"19","author":"Filbin","year":"2013","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.vph.2015.05.008","article-title":"The critical role of Akt in cardiovascular function","volume":"74","author":"Abeyrathna","year":"2015","journal-title":"Vascul. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1158\/0008-5472.CAN-07-1420","article-title":"TTI-237: A novel microtubule-active compound with in vivo antitumor activity","volume":"68","author":"Beyer","year":"2008","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cell.2014.02.021","article-title":"RETRACTED: Vulnerability of Glioblastoma Cells to Catastrophic Vacuolization and Death Induced by a Small Molecule","volume":"157","author":"Kitambi","year":"2014","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ejmech.2016.04.003","article-title":"Locking PDK1 in DFG-out conformation through 2-oxo-indole containing molecules: Another tools to fight glioblastoma","volume":"118","author":"Sestito","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1158\/1535-7163.MCT-15-0800","article-title":"ST-11: A New Brain-Penetrant Microtubule-Destabilizing Agent with Therapeutic Potential for Glioblastoma Multiforme","volume":"15","author":"Cherry","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1476-4598-10-69","article-title":"A chalcone-related small molecule that induces methuosis, a novel form of non-apoptotic cell death, in glioblastoma cells","volume":"10","author":"Overmeyer","year":"2011","journal-title":"Mol. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1021\/jm201006x","article-title":"Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of nonapoptotic cell death","volume":"55","author":"Robinson","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ejmech.2015.10.020","article-title":"Design and synthesis of 2-oxindole based multi-targeted inhibitors of PDK1\/Akt signaling pathway for the treatment of glioblastoma multiforme","volume":"105","author":"Sestito","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1021\/acschemneuro.6b00251","article-title":"Dual Inhibition of PDK1 and Aurora Kinase A: An Effective Strategy to Induce Differentiation and Apoptosis of Human Glioblastoma Multiforme Stem Cells","volume":"8","author":"Daniele","year":"2017","journal-title":"ACS Chem. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mateos, R., P\u00e9rez-Correa, J.R., and Dom\u00ednguez, H. (2020). Bioactive Properties of Marine Phenolics. Mar. Drugs, 18.","DOI":"10.3390\/md18100501"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Stien, D. (2020). Marine Microbial Diversity as a Source of Bioactive Natural Products. Mar. Drugs, 18.","DOI":"10.3390\/md18040215"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1080\/14786419.2018.1470514","article-title":"Marine natural flavonoids: Chemistry and biological activities","volume":"33","author":"Martins","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.tifs.2016.01.019","article-title":"Marine bioactive compounds and health promoting perspectives; innovation pathways for drug discovery","volume":"50","author":"Suleria","year":"2016","journal-title":"Trends Food Sci. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1039\/D0NP00089B","article-title":"Marine natural products","volume":"38","author":"Carroll","year":"2021","journal-title":"Nat. Prod. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Honek, J., and Efferth, T. (2013). Marine Compounds. Biodiversity, Natural Products and Cancer Treatment, World Scientific.","DOI":"10.1142\/9789814583510_0006"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.jsps.2019.04.013","article-title":"Natural products against cancer: Review on phytochemicals from marine sources in preventing cancer","volume":"27","author":"Wali","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ruiz-Torres, V., Encinar, J.A., Herranz-L\u00f3pez, M., P\u00e9rez-S\u00e1nchez, A., Galiano, V., Barraj\u00f3n-Catal\u00e1n, E., and Micol, V. (2017). An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs. Molecules, 22.","DOI":"10.3390\/molecules22071037"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, X., Ye, X., Chai, W., Lian, X.-Y., and Zhang, Z. (2016). New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338. Mar. Drugs, 14.","DOI":"10.3390\/md14100181"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.phytochem.2016.12.010","article-title":"Antiproliferative cyclodepsipeptides from the marine actinomycete Streptomyces sp. P11-23B downregulating the tumor metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis","volume":"135","author":"Ye","year":"2017","journal-title":"Phytochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1080\/14786419.2017.1343329","article-title":"Antiglioma pseurotin A from marine Bacillus sp. FS8D regulating tumour metabolic enzymes","volume":"32","author":"Anjum","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41598-017-18484-7","article-title":"Anti-glioma Natural Products Downregulating Tumor Glycolytic Enzymes from Marine Actinomycete Streptomyces sp. ZZ406","volume":"8","author":"Chen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.taap.2011.04.006","article-title":"Eckol suppresses maintenance of stemness and malignancies in glioma stem-like cells","volume":"254","author":"Hyun","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5130","DOI":"10.3390\/md11125130","article-title":"Fucoxanthin: A marine carotenoid exerting anti-cancer effects by affecting multiple mechanisms","volume":"11","author":"Kumar","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1055\/s-0043-111897","article-title":"Bioactive Bafilomycins and a New N-Arylpyrazinone Derivative from Marine-derived Streptomyces sp. HZP-2216E","volume":"83","author":"Zhang","year":"2017","journal-title":"Planta Med."},{"key":"ref_44","first-page":"8062","article-title":"Aplysin suppresses the invasion of glioma cells by targeting Akt pathway","volume":"9","author":"Gong","year":"2016","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/j.2042-7158.2011.01430.x","article-title":"Comparison of the effects of marchantin C and fucoidan on sFlt-1 and angiogenesis in glioma microenvironment","volume":"64","author":"Lv","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4978","DOI":"10.3390\/nu5124978","article-title":"Cancer preventive efficacy of marine carotenoid fucoxanthin: Cell cycle arrest and apoptosis","volume":"5","author":"Rengarajan","year":"2013","journal-title":"Nutrients"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.3390\/md10112388","article-title":"New capoamycin-type antibiotics and polyene acids from marine Streptomyces fradiae PTZ0025","volume":"10","author":"Xin","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1021\/acs.jnatprod.9b00481","article-title":"Bioactive Streptoglutarimides A-J from the Marine-Derived Streptomyces sp. ZZ741","volume":"82","author":"Zhang","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"W\u00e4tjen, W., Ebada, S., Bergermann, A., Chovolou, Y., Totzke, F., Kubbutat, M., Lin, W., and Chaidir, C. (2016). Cytotoxic effects of the anthraquinone derivatives 1\u2032-deoxyrhodoptilometrin and (S)-(\u2212)-rhodoptilometrin isolated from the marine echinoderm Comanthus sp.. Arch. Toxicol., 91.","DOI":"10.1007\/s00204-016-1787-7"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1475-2867-12-14","article-title":"Molecular network profiling of U373MG human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids","volume":"12","author":"Tabunoki","year":"2012","journal-title":"Cancer Cell Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1021\/np020027r","article-title":"Minor steroidal alkaloids from the marine sponge Corticium sp.","volume":"65","author":"Borbone","year":"2002","journal-title":"J. Nat. Prod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1158\/1535-7163.MCT-06-0422","article-title":"Eupalmerin acetate, a novel anticancer agent from Caribbean gorgonian octocorals, induces apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase pathway","volume":"6","author":"Iwamaru","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Neupane, R.P., Parrish, S.M., Neupane, J.B., Yoshida, W.Y., Yip, M.L.R., Turkson, J., Harper, M.K., Head, J.D., and Williams, P.G. (2019). Cytotoxic Sesquiterpenoid Quinones and Quinols, and an 11-Membered Heterocycle, Kauamide, from the Hawaiian Marine Sponge Dactylospongia elegans. Mar. Drugs, 17.","DOI":"10.3390\/md17070423"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5552","DOI":"10.3390\/md13095552","article-title":"Sphingosines Derived from Marine Sponge as Potential Multi-Target Drug Related to Disorders in Cancer Development","volume":"13","author":"Biegelmeyer","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.tet.2018.01.015","article-title":"New bioactive pyrrospirones C\u2212I from a marine-derived fungus Penicillium sp. ZZ380","volume":"74","author":"Song","year":"2018","journal-title":"Tetrahedron"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1055\/s-0034-1383404","article-title":"Bioactive sulfated saponins from sea cucumber Holothuria moebii","volume":"81","author":"Yu","year":"2015","journal-title":"Planta Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tsuji, S., Nakamura, S., Maoka, T., Yamada, T., Imai, T., Ohba, T., Yako, T., Hayashi, M., Endo, K., and Saio, M. (2020). Antitumour Effects of Astaxanthin and Adonixanthin on Glioblastoma. Mar. Drugs, 18.","DOI":"10.3390\/md18090474"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113085","DOI":"10.1016\/j.ejmech.2020.113085","article-title":"Xanthenes in Medicinal Chemistry\u2014Synthetic strategies and biological activities","volume":"210","author":"Maia","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/cmdc.201900735","article-title":"Yicathins B and C and Analogues: Total Synthesis, Lipophilicity and Biological Activities","volume":"15","author":"Loureiro","year":"2020","journal-title":"ChemMedChem"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Mahmoud, B.S., AlAmri, A.H., and McConville, C. (2020). Polymeric Nanoparticles for the Treatment of Malignant Gliomas. Cancers, 12.","DOI":"10.3390\/cancers12010175"},{"key":"ref_62","first-page":"15S","article-title":"Good Drug Therapy: It\u2019s Not Just the Molecule\u2014It\u2019s the Delivery","volume":"100","year":"2004","journal-title":"Chem. Eng. Progress"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.maturitas.2011.12.015","article-title":"Nanotechnology for neurodegenerative disorders","volume":"73","author":"Re","year":"2012","journal-title":"Maturitas"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.addr.2021.01.012","article-title":"Frontiers in the treatment of glioblastoma: Past, present and emerging","volume":"171","author":"Janjua","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3109\/03639045.2011.608191","article-title":"Nanostructure-based drug delivery systems for brain targeting","volume":"38","author":"Haque","year":"2012","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jconrel.2014.12.030","article-title":"Nanomedicine in cancer therapy: Challenges, opportunities, and clinical applications","volume":"200","author":"Wicki","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Alphandery, E. (2020). Nano-Therapies for Glioblastoma Treatment. Cancers, 12.","DOI":"10.3390\/cancers12010242"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1038\/s41467-018-04315-4","article-title":"Enhanced efficacy of combined temozolomide and bromodomain inhibitor therapy for gliomas using targeted nanoparticles","volume":"9","author":"Lam","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6674","DOI":"10.1021\/am5092165","article-title":"Temozolomide nanoparticles for targeted glioblastoma therapy","volume":"7","author":"Fang","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ijpharm.2018.04.062","article-title":"Receptor-mediated PLGA nanoparticles for glioblastoma multiforme treatment","volume":"545","author":"Ramalho","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.1002\/smll.201500540","article-title":"Combined Delivery of Temozolomide and Anti-miR221 PNA Using Mesoporous Silica Nanoparticles Induces Apoptosis in Resistant Glioma Cells","volume":"11","author":"Bertucci","year":"2015","journal-title":"Small"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.ijbiomac.2017.01.073","article-title":"A novel biocompatible drug delivery system of chitosan\/temozolomide nanoparticles loaded PCL-PU nanofibers for sustained delivery of temozolomide","volume":"97","author":"Irani","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"G\u00fcrten, B., Yenig\u00fcl, E., Sezer, A.D., Altan, C., and Malta, S. (2020). Targeting of temozolomide using magnetic nanobeads: An in vitro study. Braz. J. Pharm. Sci., 56.","DOI":"10.1590\/s2175-97902019000418579"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8511","DOI":"10.1016\/j.biomaterials.2013.07.075","article-title":"Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment","volume":"34","author":"Cui","year":"2013","journal-title":"Biomaterials"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11292","DOI":"10.1038\/s41598-020-68017-y","article-title":"Doxorubicin-loaded iron oxide nanoparticles for glioblastoma therapy: A combinational approach for enhanced delivery of nanoparticles","volume":"10","author":"Norouzi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"128","DOI":"10.2478\/jtim-2018-0025","article-title":"Nanotechnology for Treatment of Glioblastoma Multiforme","volume":"6","author":"Michael","year":"2018","journal-title":"J. Transl. Int. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jconrel.2015.09.059","article-title":"Liposome-based glioma targeted drug delivery enabled by stable peptide ligands","volume":"218","author":"Wei","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"11751","DOI":"10.1073\/pnas.1304504110","article-title":"Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma","volume":"110","author":"Zhou","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1021\/mp200600t","article-title":"Transferrin-modified c[RGDfK]-paclitaxel loaded hybrid micelle for sequential blood-brain barrier penetration and glioma targeting therapy","volume":"9","author":"Zhang","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ijpharm.2016.01.018","article-title":"Anti-glioma activity and the mechanism of cellular uptake of asiatic acid-loaded solid lipid nanoparticles","volume":"500","author":"Garanti","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Alves, A., Correia-da-Silva, M., Nunes, C., Campos, J., Sousa, E., Silva, P.M.A., Bousbaa, H., Rodrigues, F., Ferreira, D., and Costa, P.C. (2019). Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations. Molecules, 24.","DOI":"10.3390\/molecules24030409"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/9\/2707\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:57:15Z","timestamp":1760162235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/9\/2707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":81,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["molecules26092707"],"URL":"https:\/\/doi.org\/10.3390\/molecules26092707","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2021,5,5]]}}}