title: Targeted cancer therapy with a 2-deoxyglucose-based adriamycin complex.
abstract: Adriamycin (ADM) has been effective against many types of solid tumors in clinical applications. However, its use is limited because of systemic toxicities, primarily cardiotoxicity, and multidrug resistance. In this study, a new active receptor-mediated complex, ADM conjugated with 2-amino-2-deoxy-d-glucose and succinic acid (2DG-SUC-ADM), was designed to target tumor cells through glucose transporter 1 (GLUT1). MTT assay and confocal images showed that the complex had better inhibition rate to tumor cells and low toxicity to normal cells. Most importantly, the complex displayed a potential to reverse overcome multidrug resistance in cancer cells, with more complex transported into the nucleus of tumor cells. Our in vivo experiments also showed that this new complex could significantly decrease organ toxicity and enhance the antitumor efficacy compared with free ADM, indicating a promising drug of 2DG-SUC-ADM for targeted cancer therapy.
authors: Department of Biomedical Engineering, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
authors: Jie
authors: J
authors: Cao
authors: Sisi
authors: S
authors: Cui
authors: Siwen
authors: S
authors: Li
authors: Changli
authors: C
authors: Du
authors: Junmei
authors: J
authors: Tian
authors: Shunan
authors: S
authors: Wan
authors: Zhiyu
authors: Z
authors: Qian
authors: Yueqing
authors: Y
authors: Gu
authors: Wei R
authors: WR
authors: Chen
authors: Guangji
authors: G
authors: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003847:Deoxyglucose / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008956:Models, Chemical; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology; D019802:Succinic Acid / Q000737:chemistry*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D051272:Glucose Transporter Type 1; D004317:Doxorubicin; D003847:Deoxyglucose; D011794:Quercetin; D019802:Succinic Acid