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Disulfiram (DSF) is currently tested in several clinical trials for cancer treatment in combination with copper (Cu) ions. Usually, DSF and Cu are administered in two separate formulations. In the body, DSF and Cu ions form diethyldithiocarbamate copper complex [Cu(DDC)₂] which has potent antitumor activities. However, the “two formulation” approach often achieved low Cu(DDC)₂ concentration at tumor regions and resulted in compromised anticancer efficacy. Therefore, preformed Cu(DDC)₂ complex administered in a single formulation will have better anticancer efficacy. However, the poor aqueous solubility of Cu(DDC)₂ is a significant challenge for its clinical use. In this work, a biomimetic nanoparticle formulation of Cu(DDC)₂ was produced with a novel SMILE (Stabilized Metal Ion Ligand complex) method developed in our laboratory to address the drug delivery challenges. The Metal-organic Nanoparticle …