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Elesclomol (ES), a copper-binding ionophore, forms an ES–Cu complex with copper ions (Cu(II)). ES–Cu has been proven to induce mitochondrial oxidative stress and copper-dependent cell death (cuprotosis). However, ES–Cu is poorly water-soluble, and its delivery to various cancer cells is a challenge. Herein, we designed a d-α-tocopherol polyethylene glycol 1000 succinate/chondroitin sulfate-cholic acid (TPGS/CS–CA)-based micellar nanoparticle for delivering the ES–Cu complex to various cancer cell lines to demonstrate its efficacy as an anticancer agent. The ES–Cu nanoparticles exerted high encapsulation efficiency and excellent serum stability. The anticancer efficacy of ES–Cu nanoparticles was evaluated in various drug-sensitive cell lines (DU145, PC3, and A549) and drug-resistant cell lines (DU145TXR, PC3TXR, and A549TXR). The results showed that ES–Cu nanoparticles exerted potent …