A Ferritin–Albumin–Cu Nanoparticle that Efficaciously Delivers Copper(II) Ions to a Tumor and Improves the Therapeutic Efficacy of Disulfiram

[Image: see text] The application of disulfiram can be traced back to the 1920s, from when it was utilized to facilitate alcohol abstinence by producing allergic reactions toward alcohol. In previous research, combination of disulfiram and copper ions has demonstrated significant anti-tumor activity. However, both disulfiram and copper ions lack the ability of specific targeting to tumor tissues and may lead to a high risk of side effects, especially for copper ion, which is a kind of toxic heavy metal. Herein, a ferritin–albumin–Cu nanoparticle (FHC NP) was introduced. The nanoparticle was synthesized by first covalently cross-linking ferritin and albumin and then encapsulating the copper ions in the ferritin nanocage. The nanoparticle showed good accumulation in a tumor and when combined with disulfiram exhibited good in vitro selectivity toward cancer cells and better in vivo anti-tumor activity. Herein, the nanoparticle invented here represented a good strategy to efficaciously deliver copper ions into tumors and thus improve the therapeutic efficacy of disulfiram in tumor therapy.