{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:21:25Z","timestamp":1782890485276,"version":"3.54.5"},"reference-count":66,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Lodz","award":["503\/6-086-01\/503-61-001-19-00"],"award-info":[{"award-number":["503\/6-086-01\/503-61-001-19-00"]}]},{"name":"Medical University of Lodz","award":["503\/6-086-01\/503-61-001"],"award-info":[{"award-number":["503\/6-086-01\/503-61-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tumor therapy escape due to undesired side effects induced by treatment, such as prosurvival autophagy or cellular senescence, is one of the key mechanisms of resistance that eventually leads to tumor dormancy and recurrence. Glioblastoma is the most frequent and practically incurable neoplasm of the central nervous system; thus, new treatment modalities have been investigated to find a solution more effective than the currently applied standards based on temozolomide. The present study examined the newly synthesized compounds of aziridine\u2013hydrazide hydrazone derivatives to determine their antineoplastic potential against glioblastoma cells in vitro. Although the output of our investigation clearly demonstrates their proapoptotic activity, the cytotoxic effect appeared to be blocked by treatment-induced autophagy, the phenomenon also detected in the case of temozolomide action. The addition of an autophagy inhibitor, chloroquine, resulted in a significant increase in apoptosis triggered by the tested compounds, as well as temozolomide. The new aziridine\u2013hydrazide hydrazone derivatives, which present cytotoxic potential against glioblastoma cells comparable to or even higher than that of temozolomide, show promising results and, thus, should be further investigated as antineoplastic agents. Moreover, our findings suggest that the combination of an apoptosis inducer with an autophagy inhibitor could optimize chemotherapeutic efficiency, and the addition of an autophagy inhibitor should be considered as an optional adjunctive therapy minimizing the risk of tumor escape from treatment.<\/jats:p>","DOI":"10.3390\/cells12141906","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T01:08:11Z","timestamp":1690160891000},"page":"1906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Autophagy Inhibition with Chloroquine Increased Pro-Apoptotic Potential of New Aziridine-Hydrazide Hydrazone Derivatives against Glioblastoma Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-2859","authenticated-orcid":false,"given":"Monika","family":"Witusik-Perkowska","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 6\/8 Mazowiecka Str., 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pola","family":"G\u0142owacka","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 6\/8 Mazowiecka Str., 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6526-315X","authenticated-orcid":false,"given":"Adam M.","family":"Pieczonka","sequence":"additional","affiliation":[{"name":"Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4866-5485","authenticated-orcid":false,"given":"Ewa","family":"\u015awiderska","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 6\/8 Mazowiecka Str., 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5935-7432","authenticated-orcid":false,"given":"Agnieszka","family":"Pudlarz","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 6\/8 Mazowiecka Str., 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4803-8078","authenticated-orcid":false,"given":"Micha\u0142","family":"Rachwalski","sequence":"additional","affiliation":[{"name":"Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Szyma\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Zakrzewska","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz J.","family":"Jask\u00f3lski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Medical University of Lodz, Barlicki University Hospital, Kopcinskiego 22, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6052-3557","authenticated-orcid":false,"given":"Janusz","family":"Szemraj","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 6\/8 Mazowiecka Str., 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1007\/s12094-016-1497-x","article-title":"Survival in Glioblastoma: A Review on the Impact of Treatment Modalities","volume":"18","year":"2016","journal-title":"Clin. Transl. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1172\/JCI89587","article-title":"Overcoming Therapeutic Resistance in Glioblastoma: The Way Forward","volume":"127","author":"Osuka","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vollmann-Zwerenz, A., Leidgens, V., Feliciello, G., Klein, C.A., and Hau, P. (2020). Tumor Cell Invasion in Glioblastoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061932"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ferri, A., Stagni, V., and Baril\u00e0, D. (2020). Targeting the DNA Damage Response to Overcome Cancer Drug Resistance in Glioblastoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144910"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Santamar\u00eda, P.G., Moreno-Bueno, G., and Cano, A. (2019). Contribution of Epithelial Plasticity to Therapy Resistance. J. Clin. Med., 8.","DOI":"10.3390\/jcm8050676"},{"key":"ref_6","first-page":"66","article-title":"Role of Autophagy in Therapeutic Resistance of Glioblastoma","volume":"5","author":"Chien","year":"2019","journal-title":"J. Cancer Metastasis Treat."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Saleh, T., Bloukh, S., Carpenter, V.J., Alwohoush, E., Bakeer, J., Darwish, S., Azab, B., and Gewirtz, D.A. (2020). Therapy-Induced Senescence: An \u201cOld\u201d Friend Becomes the Enemy. Cancers, 12.","DOI":"10.3390\/cancers12040822"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.trecan.2020.05.004","article-title":"Senescent Cells in Cancer Therapy: Friends or Foes?","volume":"6","author":"Wang","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_9","first-page":"17","article-title":"Mechanisms of Temozolomide Resistance in Glioblastoma\u2014A Comprehensive Review","volume":"4","author":"Singh","year":"2021","journal-title":"Cancer Drug Resist."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S0006-2952(00)00380-4","article-title":"Induction of Oxidative Stress and Apoptosis in Myeloma Cells by the Aziridine-Containing Agent Imexon","volume":"60","author":"Dvorakova","year":"2000","journal-title":"Biochem. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1016\/j.ejmech.2009.05.013","article-title":"Aziridine Alkaloids as Potential Therapeutic Agents","volume":"44","author":"Ismail","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ramawat, K.G., and M\u00e9rillon, J.-M. (2013). Natural Products: Phytochemistry, Botany and Metabolism of Alkaloids, Phenolics and Terpenes, Springer.","DOI":"10.1007\/978-3-642-22144-6"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.bioorg.2017.10.016","article-title":"Azole-Hydrazone Derivatives: Design, Synthesis, in Vitro Biological Evaluation, Dual EGFR\/HER2 Inhibitory Activity, Cell Cycle Analysis and Molecular Docking Study as Anticancer Agents","volume":"76","author":"Labib","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.bmc.2019.02.002","article-title":"Synthesis, Antiproliferative and Apoptosis Induction Potential Activities of Novel Bis(Indolyl)Hydrazide-Hydrazone Derivatives","volume":"27","author":"Sreenivasulu","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.ejmech.2012.10.011","article-title":"Synthesis and Biological Evaluation of Some Hydrazone Derivatives as New Anticandidal and Anticancer Agents","volume":"58","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.3390\/12081910","article-title":"Biological Activities of Hydrazone Derivatives","volume":"12","author":"Rollas","year":"2007","journal-title":"Molecules"},{"key":"ref_17","first-page":"162","article-title":"A Review on Biological Activities of Hydrazone Derivatives","volume":"6","author":"Singh","year":"2016","journal-title":"Int. J. Pharm. Clin. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"342","DOI":"10.2174\/1389557519666191014142448","article-title":"Synthesis and Biological Activity of Hydrazones and Derivatives: A Review","volume":"20","author":"LaPlante","year":"2020","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kowalczyk, A., Pieczonka, A.M., Rachwalski, M., Le\u015bniak, S., and St\u0105czek, P. (2018). Synthesis and Evaluation of Biological Activities of Aziridine Derivatives of Urea and Thiourea. Molecules, 23.","DOI":"10.3390\/molecules23010045"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.ejmech.2013.04.023","article-title":"Synthesis and Evaluation of Antimicrobial Activity of Hydrazones Derived from 3-Oxido-1H-Imidazole-4-Carbohydrazides","volume":"64","author":"Pieczonka","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1016\/j.bmcl.2018.07.015","article-title":"N-Acylhydrazones as Drugs","volume":"28","author":"Thota","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A Summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12935-014-0082-z","article-title":"Astrocytoma-Associated Antigens\u2014IL13R\u03b12, Fra-1, and EphA2 as Potential Markers to Monitor the Status of Tumour-Derived Cell Cultures in Vitro","volume":"14","author":"Zakrzewska","year":"2014","journal-title":"Cancer Cell Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"BSR20170058","DOI":"10.1042\/BSR20170058","article-title":"Glioblastoma-Derived Cells in Vitro Unveil the Spectrum of Drug Resistance Capability\u2014Comparative Study of Tumour Chemosensitivity in Different Culture Systems","volume":"37","author":"Zakrzewska","year":"2017","journal-title":"Biosci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.tetasy.2013.09.006","article-title":"Synthesis and Evaluation of the Catalytic Properties of Semicarbazides Derived from N-Triphenylmethyl-Aziridine-2-Carbohydrazides","volume":"24","author":"Pieczonka","year":"2013","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.4161\/auto.21028","article-title":"A Novel Image-Based Cytometry Method for Autophagy Detection in Living Cells","volume":"8","author":"Chan","year":"2012","journal-title":"Autophagy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.4161\/15548627.2014.973338","article-title":"Defining and Measuring Autophagosome Flux\u2014Concept and Reality","volume":"10","author":"Loos","year":"2014","journal-title":"Autophagy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"542","DOI":"10.4161\/auto.4600","article-title":"How to Interpret LC3 Immunoblotting","volume":"3","author":"Mizushima","year":"2007","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (4th Edition)1","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9824","DOI":"10.1021\/acs.jmedchem.9b01220","article-title":"The Blood\u2013Brain Barrier (BBB) Score","volume":"62","author":"Gupta","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4155\/fmc.15.166","article-title":"Leaving the Lysosome behind: Novel Developments in Autophagy Inhibition","volume":"8","author":"Solitro","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine Inhibits Autophagic Flux by Decreasing Autophagosome-Lysosome Fusion","volume":"14","author":"Mauthe","year":"2018","journal-title":"Autophagy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105780","DOI":"10.1016\/j.phrs.2021.105780","article-title":"Glioblastoma Multiforme (GBM): An Overview of Current Therapies and Mechanisms of Resistance","volume":"171","author":"Wu","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Szklener, K., Mazurek, M., Wieteska, M., Wac\u0142awska, M., Bilski, M., and Ma\u0144dziuk, S. (2022). New Directions in the Therapy of Glioblastoma. Cancers, 14.","DOI":"10.3390\/cancers14215377"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pawlowska, E., Szczepanska, J., Szatkowska, M., and Blasiak, J. (2018). An Interplay between Senescence, Apoptosis and Autophagy in Glioblastoma Multiforme\u2014Role in Pathogenesis and Therapeutic Perspective. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030889"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Beltzig, L., Schwarzenbach, C., Leukel, P., Frauenknecht, K.B.M., Sommer, C., Tancredi, A., Hegi, M.E., Christmann, M., and Kaina, B. (2022). Senescence Is the Main Trait Induced by Temozolomide in Glioblastoma Cells. Cancers, 14.","DOI":"10.3390\/cancers14092233"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Hern\u00e1ndez, M., Arias, A., Mart\u00ednez-Garc\u00eda, D., P\u00e9rez-Tom\u00e1s, R., Quesada, R., and Soto-Cerrato, V. (2019). Targeting Autophagy for Cancer Treatment and Tumor Chemosensitization. Cancers, 11.","DOI":"10.3390\/cancers11101599"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"408","DOI":"10.3389\/fphar.2020.00408","article-title":"Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy","volume":"11","author":"Liu","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Espinos, E., Lai, R., and Giuriato, S. (2021). The Dual Role of Autophagy in Crizotinib-Treated ALK+ ALCL: From the Lymphoma Cells Drug Resistance to Their Demise. Cells, 10.","DOI":"10.3390\/cells10102517"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E12","DOI":"10.3171\/2014.9.FOCUS14504","article-title":"Chloroquine Enhances Temozolomide Cytotoxicity in Malignant Gliomas by Blocking Autophagy","volume":"37","author":"Golden","year":"2014","journal-title":"Neurosurg. Focus"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13046-016-0303-5","article-title":"Targeting Autophagy to Sensitive Glioma to Temozolomide Treatment","volume":"35","author":"Yan","year":"2016","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5721","DOI":"10.1021\/jm900722z","article-title":"Procaspase-3 Activation as an Anti-Cancer Strategy: Structure-Activity Relationship of Procaspase-Activating Compound 1 (PAC-1) and Its Cellular Co-Localization with Caspase-3","volume":"52","author":"Peterson","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jmb.2009.03.003","article-title":"PAC-1 Activates Procaspase-3 in Vitro through Relief of Zinc-Mediated Inhibition","volume":"388","author":"Peterson","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.7150\/ijbs.9719","article-title":"Caspases: A Molecular Switch Node in the Crosstalk between Autophagy and Apoptosis","volume":"10","author":"Wu","year":"2014","journal-title":"Int. J. Biol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.canlet.2015.02.012","article-title":"The Synergistic Effect of Combination Temozolomide and Chloroquine Treatment Is Dependent on Autophagy Formation and P53 Status in Glioma Cells","volume":"360","author":"Lee","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1038\/cdd.2017.43","article-title":"Caspase Involvement in Autophagy","volume":"24","author":"Tsapras","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10633","DOI":"10.1021\/acsomega.0c00830","article-title":"Contribution of Organofluorine Compounds to Pharmaceuticals","volume":"5","author":"Inoue","year":"2020","journal-title":"ACS Omega"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1080\/14737175.2016.1202761","article-title":"Blood-Brain Barrier, Cytotoxic Chemotherapies and Glioblastoma","volume":"16","author":"Goldwirt","year":"2016","journal-title":"Expert Rev. Neurother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ccell.2014.10.006","article-title":"Antiangiogenesis Strategies Revisited: From Starving Tumors to Alleviating Hypoxia","volume":"26","author":"Jain","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1002\/jps.24329","article-title":"In Vitro Blood\u2013Brain Barrier Models\u2014An Overview of Established Models and New Microfluidic Approaches","volume":"104","author":"Wolff","year":"2015","journal-title":"J. Pharm. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Foo, C.Y., Munir, N., Kumaria, A., Akhtar, Q., Bullock, C.J., Narayanan, A., and Fu, R.Z. (2022). Medical Device Advances in the Treatment of Glioblastoma. Cancers, 14.","DOI":"10.3390\/cancers14215341"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/neuonc\/nop054","article-title":"Phase III Randomized Trial of CED of IL13-PE38QQR vs Gliadel Wafers for Recurrent Glioblastoma\u2020","volume":"12","author":"Kunwar","year":"2010","journal-title":"Neuro Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.neurol.2023.03.013","article-title":"Overcoming the Blood Brain Barrier in Glioblastoma: Status and Future Perspective","volume":"179","author":"Ahmed","year":"2023","journal-title":"Rev. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/neuonc\/5.2.96","article-title":"A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of RMP-7 in Combination with Carboplatin Administered Intravenously for the Treatment of Recurrent Malignant Glioma","volume":"5","author":"Prados","year":"2003","journal-title":"Neuro Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1158\/1541-7786.MCR-19-0995","article-title":"Adenosine A2A Receptor Activation Enhances Blood\u2013Tumor Barrier Permeability in a Rodent Glioma Model","volume":"19","author":"Manglani","year":"2021","journal-title":"Mol. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"114820","DOI":"10.1016\/j.addr.2023.114820","article-title":"Engineered Nanomaterials That Exploit Blood-Brain Barrier Dysfunction for Delivery to the Brain","volume":"197","author":"Wu","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"15330338221080974","DOI":"10.1177\/15330338221080974","article-title":"Nanocarriers Call the Last Shot in the Treatment of Brain Cancers","volume":"21","author":"Mehrabian","year":"2022","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.drudis.2011.02.006","article-title":"Supramolecular Devices to Improve the Treatment of Brain Diseases","volume":"16","author":"Paolino","year":"2011","journal-title":"Drug Discov. Today"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wong, K.H., Riaz, M.K., Xie, Y., Zhang, X., Liu, Q., Chen, H., Bian, Z., Chen, X., Lu, A., and Yang, Z. (2019). Review of Current Strategies for Delivering Alzheimer\u2019s Disease Drugs across the Blood-Brain Barrier. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020381"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e1695","DOI":"10.1002\/wnan.1695","article-title":"Brain Penetrating Peptides and Peptide\u2013Drug Conjugates to Overcome the Blood\u2013Brain Barrier and Target CNS Diseases","volume":"13","author":"Zhou","year":"2021","journal-title":"WIREs Nanomed. Nanobiotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1158\/1078-0432.CCR-07-1990","article-title":"Interleukin-13 Receptor Alpha 2, EphA2, and Fos-Related Antigen 1 as Molecular Denominators of High-Grade Astrocytomas and Specific Targets for Combinatorial Therapy","volume":"14","author":"Wykosky","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1093\/neuonc\/nor141","article-title":"An Interleukin 13 Receptor \u03b1 2\u2013Specific Peptide Homes to Human Glioblastoma Multiforme Xenografts","volume":"14","author":"Pandya","year":"2012","journal-title":"Neuro Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3905","DOI":"10.2147\/OTT.S190601","article-title":"Artificial Microenvironment of in Vitro Glioblastoma Cell Cultures Changes Profile of MiRNAs Related to Tumor Drug Resistance","volume":"12","author":"Zakrzewska","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1038\/srep02534","article-title":"Ligand Modified Nanoparticles Increases Cell Uptake, Alters Endocytosis and Elevates Glioma Distribution and Internalization","volume":"3","author":"Gao","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1158\/1535-7163.MCT-06-0480","article-title":"Interleukin-13 Receptor-Targeted Nanovesicles Are a Potential Therapy for Glioblastoma Multiforme","volume":"5","author":"Madhankumar","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.colsurfb.2016.08.002","article-title":"PEGylated Polyamidoamine Dendrimer Conjugated with Tumor Homing Peptide as a Potential Targeted Delivery System for Glioma","volume":"147","author":"Jiang","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/14\/1906\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:16:30Z","timestamp":1760127390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/14\/1906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,21]]},"references-count":66,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["cells12141906"],"URL":"https:\/\/doi.org\/10.3390\/cells12141906","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,21]]}}}