title: Kinetics and efficiency of a methyl-carboxylated 5-Fluorouracil-bovine serum albumin adduct for targeted delivery.
abstract: 5-Fluorouracil (5-FU) is a clinically well-established anti-cancer drug effectively applied in chemotherapy, mainly for the treatment of breast and colorectal cancer. Substantial disadvantages are adverse effects, arising from serious damage of healthy tissues, and shortcoming pharmacokinetics due to its low molecular weight. A promising approach for improvement of such drugs is their coupling to suitable carriers. Here, a 5-FU adduct, 5-fluorouracil acetate (FUAc) is synthesized and covalently coupled to bovine serum albumin (BSA) as model carrier molecule. On average, 12 molecules FUAc are bound to one BSA. Circular dichriosm (CD)-spectra of BSA and FUAc-BSA are identical, suggesting no significant conformational differences. FUAc-BSA is tested on T-47D and MDA-MB-231 breast cancer cells. Proliferation inhibition of membrane albumin-binding protein (mABP)-expressing T-47D cells by FUAc-BSA is similar to that of 5-FU and only moderate for MDA-MB-231 cells that lack such expression. Therefore, a crucial role of mABP expression in effective cell growth inhibition by FUAc-BSA is assumed.
authors.affiliation: Institute of Transfusion Medicine, Center for Tumor Medicine, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Koziol
authors.forename: Torsten K
authors.initials: TK
authors.lastname: Sievers
authors.forename: Kathrin
authors.initials: K
authors.lastname: Smuda
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiong
authors.forename: Angelika
authors.initials: A
authors.lastname: Müller
authors.forename: Felix
authors.initials: F
authors.lastname: Wojcik
authors.forename: Axel
authors.initials: A
authors.lastname: Steffen
authors.forename: Margitta
authors.initials: M
authors.lastname: Dathe
authors.forename: Radostina
authors.initials: R
authors.lastname: Georgieva
authors.forename: Hans
authors.initials: H
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D009928:Organ Specificity; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012795:Sialoglycoproteins; C065610:sialoglycoprotein gp60; D012710:Serum Albumin, Bovine; D005472:Fluorouracil
keywords: 5-fluorouracil; MALDI; albumin; drug delivery systems; human breast cancer cell lines