{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:03:08Z","timestamp":1790787788297,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The BCURED Foundation","award":["21L08"],"award-info":[{"award-number":["21L08"]}]},{"name":"Mystic Force Foundation","award":["21L08"],"award-info":[{"award-number":["21L08"]}]},{"DOI":"10.13039\/100006827","name":"Florida Department of Health Live Like Bella","doi-asserted-by":"publisher","award":["21L08"],"award-info":[{"award-number":["21L08"]}],"id":[{"id":"10.13039\/100006827","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The current prognosis for glioblastoma is dismal. Treatment-resistant glioblastoma stem cells (GSCs) and the failure of most drugs to reach therapeutic levels within the tumor remain formidable obstacles to successful treatment. Chalcones are aromatic ketones demonstrated to reduce malignant properties in cancers including glioblastoma. Nanomedicines can increase drug accumulation and tumor cell death. Carbon-dots are promising nanocarriers that can be easily functionalized with tumor-targeting ligands and anti-cancer drugs. Therefore, we synthesized a series of 4\u2032-amino chalcones with the rationale that the amino group would serve as a \u201chandle\u201d to facilitate covalent attachment to carbon-dots and tested their cytotoxicity toward GSCs. We generated 31 chalcones (22 4\u2032-amino and 9 4\u2032 derivatives) including 5 novel chalcones, and found that 13 had an IC50 below 10 \u00b5M in all GSC lines. After confirming that the 4-amino group was not part of the active pharmacophore, chalcones were attached to transferrin-conjugated carbon-dots. These conjugates were significantly more cytotoxic than the free chalcones, with the C-dot-transferrin-2,5, dimethoxy chalcone conjugate inducing up to 100-fold more GSC death. Several of the tested chalcones represent promising lead compounds for the development of novel anti-GSC drugs. Furthermore, designing amino chalcones for carbon-dot mediated drug delivery is a rational and effective methodology.<\/jats:p>","DOI":"10.3390\/pharmaceutics14071465","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T01:57:11Z","timestamp":1657850231000},"page":"1465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Chalcones as Anti-Glioblastoma Stem Cell Agent Alone or as Nanoparticle Formulation Using Carbon Dots as Nanocarrier"],"prefix":"10.3390","volume":"14","author":[{"given":"Eduardo A.","family":"Veliz","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146, USA"},{"name":"Department of Natural Sciences, Miami Dade College, 300 NE Second Ave, Miami, FL 33132, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia","family":"Kaplina","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146, USA"},{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4063-1355","authenticated-orcid":false,"given":"Sajini D.","family":"Hettiarachchi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athina L.","family":"Yoham","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"},{"name":"University of Miami Brain Tumor Initiative, Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Matta","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrin","family":"Safar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghana","family":"Sankaran","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther L.","family":"Abadi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emel Kirbas","family":"Cilingir","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic A.","family":"Vallejo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"},{"name":"University of Miami Brain Tumor Initiative, Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winston M.","family":"Walters","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"},{"name":"University of Miami Brain Tumor Initiative, Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Vanni","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"},{"name":"HCA Florida University Hospital, 3476 S University Dr., Davie, FL 33328, USA"},{"name":"Department of Medicine, Dr. Kiran C. Patel College of Allopathic Medicine, Davie, FL 33328, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger M.","family":"Leblanc","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0103-2971","authenticated-orcid":false,"given":"Regina M.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"},{"name":"University of Miami Brain Tumor Initiative, Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1475 NW 12th Ave, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1470-2045(09)70025-7","article-title":"Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial","volume":"10","author":"Stupp","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.gendis.2015.02.001","article-title":"Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs","volume":"2","author":"Safa","year":"2015","journal-title":"Genes Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7843","DOI":"10.1158\/0008-5472.CAN-06-1010","article-title":"Stem Cell\u2013like Glioma Cells Promote Tumor Angiogenesis through Vascular Endothelial Growth Factor","volume":"66","author":"Bao","year":"2006","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nature09624","article-title":"Glioblastoma stem-like cells give rise to tumour endothelium","volume":"468","author":"Wang","year":"2010","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nrc1092","article-title":"Vasculogenic mimicry and tumour-cell plasticity: Lessons from melanoma","volume":"3","author":"Hendrix","year":"2003","journal-title":"Nat. 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