{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:08:33Z","timestamp":1785294513120,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005632","name":"National Centre for Research and Development","doi-asserted-by":"publisher","award":["TANGO3\/426098\/NCBR\/2019"],"award-info":[{"award-number":["TANGO3\/426098\/NCBR\/2019"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"publisher","award":["STM.A210.20.118"],"award-info":[{"award-number":["STM.A210.20.118"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methotrexate (MTX) is a commonly used antimetabolite, which inhibits folate and DNA synthesis to be effective in the treatment of various malignancies. However, MTX therapy is hindered by the lack of target tumor selectivity. We have designed, synthesized and evaluated a novel glucose\u2013methotrexate conjugate (GLU\u2013MTX) both in vitro and in vivo, in which a cleavable linkage allows intracellular MTX release after selective uptake through glucose transporter\u22121 (GLUT1). GLU\u2013MTX inhibited the growth of colorectal (DLD-1), breast (MCF-7) and lung (A427) adenocarcinomas, squamous cell carcinoma (SCC-25), osteosarcoma (MG63) cell lines, but not in WI-38 healthy fibroblasts. In tumor cells, GLU\u2013MTX uptake increased 17-fold compared to unconjugated MTX. 4,6-O-ethylidene-\u03b1-D-glucose (EDG), a GLUT1 inhibitor, significantly interfered with GLU\u2013MTX induced growth inhibition, suggesting a glucose-mediated drug uptake. Glu-MTX also caused significant tumor growth delay in vivo in breast cancer-bearing mice. These results show that our GLUT-MTX conjugate can be selectively uptake by a range of tumor cells to cause their significant growth inhibition in vitro, which was also confirmed in a breast cancer model in vivo. GLUT1 inhibitor EDG interfered with these effects verifying the selective drug uptake. Accordingly, GLU\u2013MTX offers a considerable tumor selectivity and may offer cancer growth inhibition at reduced toxicity.<\/jats:p>","DOI":"10.3390\/ijms22041748","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T04:33:46Z","timestamp":1612931626000},"page":"1748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["In Vitro and In Vivo Efficacy of a Novel Glucose\u2013Methotrexate Conjugate in Targeted Cancer Treatment"],"prefix":"10.3390","volume":"22","author":[{"given":"Marta","family":"Wo\u017aniak","sequence":"first","affiliation":[{"name":"Department of Pathology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8753-1143","authenticated-orcid":false,"given":"Gabriela","family":"Pastuch-Gawo\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, 44-100 Gliwice, Poland"},{"name":"Biotechnology Centre, Silesian University of Technology, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9904-1181","authenticated-orcid":false,"given":"Sebastian","family":"Makuch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2831-7643","authenticated-orcid":false,"given":"Jerzy","family":"Wi\u015bniewski","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Wroclaw Medical University, 50-367 Wroclaw, Poland"},{"name":"Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Kren\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-3564","authenticated-orcid":false,"given":"Peter","family":"Hamar","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Gamian","sequence":"additional","affiliation":[{"name":"Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wies\u0142aw","family":"Szeja","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Szkudlarek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7400-3488","authenticated-orcid":false,"given":"Monika","family":"Krawczyk","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, 44-100 Gliwice, Poland"},{"name":"Biotechnology Centre, Silesian University of Technology, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1118-5090","authenticated-orcid":false,"given":"Siddarth","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Pathology, Wroclaw Medical University, 50-367 Wroclaw, Poland"},{"name":"Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1517\/17425247.2012.642362","article-title":"Methotrexate: A detailed review on drug delivery and clinical aspects","volume":"9","author":"Khan","year":"2012","journal-title":"Expert Opin. 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