Apoferritin as a Carrier of Cu(II) Diethyldithiocarbamate and Biomedical Application for Glutathione-Responsive Combination Chemotherapy.

The antialcoholic drug disulfiram (DSF) has attractive biomedical interests for its anticancer effects, particularly in combination use with copper. CuET, the complex of copper and diethyldithiocarbamate (DTC) that is derived from disulfiram, exhibits high redox stability against glutathione, cysteine, and hydrogen peroxide, but appears reactive to ascorbic acid and superoxide ions. By virtue of the copper binding property, apoferritin is developed as a carrier of CuET to alleviate concerns of poor water solubility and nonspecific toxicity and shows superior stability and protection over human serum albumin in nanocomposite manipulation. CuET and doxorubicin are codelivered by apoferritin with excellent efficiency (>97%). The glutathione-responsive system demonstrates enhanced antitumor effect and potentials for combination tumor therapy.