Copper coordination compounds in the nanomedicine era: from limitations to transformative cancer therapies and beyond

Abstract

The convergence of copper coordination chemistry and nanomedicine is catalyzing a transformative shift in metal-based therapeutics, addressing long-standing pharmacological barriers that have hindered clinical translation. Copper coordination compounds (CCCs) have long been recognized for their therapeutic potential, particularly in oncology, owing to their ability to generate reactive oxygen species and localize to mitochondria. However, their clinical application has been limited by poor aqueous solubility, systemic off-target toxicity, and rapid in vivo clearance. This review examines how the strategic integration of CCCs with diverse nanocarrier platforms overcomes these obstacles, unlocking unprecedented therapeutic potential. Surveying the past five years of literature, we demonstrate that nanoformulation dramatically enhances anticancer activity against treatment-resistant malignancies, through mechanisms ranging from immunogenic cell death to the recently elucidated cuproptosis pathway. The repurposed disulfiram‑copper complex serves as a paradigmatic case study, illustrating how nanoencapsulation transforms a poorly bioavailable agent into a potent therapeutic. Beyond oncology, we explore expanding applications of CCC nanomaterials as antimicrobial agents, wound-healing dressings, and advanced diagnostic tools. The studies discussed here are very recent and predominantly preclinical; nevertheless, we discuss their potential for clinical translation. This review provides a forward-looking perspective on critical challenges: long-term toxicity, large-scale manufacturability, translational hurdles, and the opportunities for these sophisticated hybrid materials to redefine precision medicine across multiple disease contexts.