Trace Element Nanoparticles for Neurodegenerative Disease Therapy

Neurodegenerative diseases (NDDs) are closely linked to physiological conditions such as oxidative stress, neuroinflammation, neuronal cell death, and proteostatic failure, all of which are associated with cerebral trace-element imbalance. Recent research has highlighted the potential of trace-element-based interventions due to their diverse redox, anti-inflammatory, and pro-survival bioactivities. Leveraging nanotechnology to construct trace-element-based nanotherapeutics capable of crossing the blood-brain barrier, actively targeting neurons, and enabling on-demand payload release has emerged as a promising strategy, transforming empirical supplementation into a precision nanomedicine approach. These nanoplatforms have demonstrated significant effects in disease treatment. However, systematic studies on their application in NDD therapy remain limited. In this review, we provide a comprehensive overview of trace-element-based nanotherapeutics, exploring how trace-metal imbalances contribute to NDD development, nanoparticle construction, and the advantages of trace-element-based nanoparticles. Additionally, we discuss the physiological aspects of trace-element metabolism and inflammation in NDD treatment, offer recommendations for future research, and comprehensively discuss and systematically evaluate the safety of trace-element nanoparticles. In doing so, we provide a resource that will help to guide the design and development of nanotherapeutics for NDDs and assist researchers in this emerging field.