Complexes of сarboxymethylcellulose with Cu2+-ions as a prototype of antitumor agent

Abstract The search for new promising carries and vectors for the purposes of nuclear medicine with multifunctional effects is the most difficult problem in this branch of medicine. Among the components that are used to create carriers, one of the most perspective is the polysaccharide carboxymethylcellulose (CMC). This choice is due to CMC high solubility in aqueous and saline solutions, low toxicity, high biocompatibility, as well as the content of a large number of anionic (carboxyl) and hydroxyl functional groups, which are capable of strong binding of polyvalent metal ions. In our work CMC were bound to Cu2+ ions that resulted in a collapse of the polymer macromolecule and formation of the CMC-Cu2+ binary complexes. The binary complexes additionally adsorbed 2-aminopyrimidine (AP) and formed the CMC-Cu2+-AP ternary complexes. The binary and ternary complexes were characterized by dynamic light scattering, laser electrophoresis, UV-spectrophotometry, TEM- microscopy, thin layer chromatography and cell viability with the following main conclusions: (a) An increase in the copper content from up to 20 wt.% leads to altering the size of CMC particles in water solution from 400 to 340 nm. Further binding of AP has no effect on the particle size. (b) In physiological solution, the size of the ternary complex particles was additionally decreased down to 200-220 nm. (c) The complex particles are stable against aggregation in water surrounding due to their total negative charge. (d) Their cytotoxicity in relation to leukemic cells significantly exceeds that in relation to normal lymphocytes, creating an attractive therapeutic window. The results show good prospects for the CMC-copper complexes as drug carriers.