Nanomedicine targets endogenous copper ions for disease diagnosis and therapy

Copper ion is an essential microelement that plays vital roles in a wide range of physiological processes, and aberrant copper levels in vivo usually cause various diseases, making it an important target for disease diagnosis and therapy. Traditional copper ion detection for disease diagnosis is mainly based on combining tissue biopsy and inductively coupled plasma spectrometry technique, while this strategy is invasive, expensive, and can't reflect copper levels in real-time, on-site, and through systematic analysis. On the other hand, copper chelators or ionophores are traditionally used to manipulate copper levels to help repair damaged cells or kill malignant cells. However, currently developed copper chelators/ionophores suffer from non-targeting ability, low bioavailability, poor selectivity, and short half-life time. Therefore, new techniques for detecting and regulating endogenous copper homeostasis are urgently demanded. Nanotechnology has dramatically advanced in improving imaging contrast, enhancing therapeutic effects, lowering side effects, etc. Early studies that combined nanotechnology with imaging/therapeutic approaches targeting copper homeostasis have shown great potential for developing diagnosis/treatment options. This review systematically summarizes recent advances in copper ion-related nanomedicine for disease diagnosis and therapy, and analyzes the underlying critical concerns, unresolved issues, and future perspectives, hoping it can provide a general implication for further research