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Casiopeins are a group of anticancer agents that are coordination complexes with copper as the metallic center. Cas III-ia has shown greater antineoplastic potency in vitroand in vivothan cisplatin on a variety of tumor cell lines. The objective of this study was to assess tumor growth inhibition by Casiopein III-ia (CasIII-ia) loaded into chitosan nanoparticles prepared by a coacervation process using both sodium hydroxide and sodium citrate as neutralizing agents. Nanoparticles were characterized by dynamic light scattering, scanning electron microscopy, differential scanning calorimetry, x-ray powder diffraction and infrared spectroscopy. Nanoparticles formed with sizes from 150 nm to 10 μm, depending on the process conditions. Instrumental analysis suggests that CasIII-ia was loaded into nanoparticles; however, the encapsulation percentage was low due to hydrophilicity. Even so, increase life span in CB6F1/Hsd mice transplanted with B16 melanoma tumors was six times for CasIII-ia loaded nanoparticles compared to the free drug. Moreover, CS-folic acid nanoparticles inhibited tumor growth up to nine times more than chitosan nanoparticles and thirteen times more than the free drug. CasIII-ia loaded into chitosan and chitosan-folic acid nanoparticles may reduce chemotherapy side effects and enhance therapeutic efficacy by targeting tumors.