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Kinetics and Efficiency of a Methyl‐ C arboxylated 5‐ F luorouracil‐ B ovine Serum Albumin Adduct for Targeted Delivery
Author(s) -
Koziol Michael J.,
Sievers Torsten K.,
Smuda Kathrin,
Xiong Yu,
Müller Angelika,
Wojcik Felix,
Steffen Axel,
Dathe Margitta,
Georgieva Radostina,
Bäumler Hans
Publication year - 2014
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201300363
Subject(s) - bovine serum albumin , chemistry , pharmacokinetics , serum albumin , albumin , pharmacology , adduct , drug delivery , biochemistry , microbiology and biotechnology , biology , organic chemistry
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.