Engineering Autonomous Micro-/Nanorobots for Neurological Diseases: From Barrier Crossing to Neuroenergetic Restoration.

Abstract

Neurological diseases (NDs) are associated with barrier transport dysfunction, abnormal protein aggregation, and impaired cellular energy metabolism, with bioenergetic deficits increasingly recognized as a central factor in disease progression. Micro-/nanorobots offer a promising strategy to address these challenges by enabling active and targeted regulation of neuronal metabolism. Unlike passive nanocarriers, micro-/nanorobots can cross the blood-brain barrier (BBB) under external guidance and deliver therapeutic agents with subcellular precision. By integrating mitochondrial-targeting components, ATP-generating modules, and redox- or ion-responsive release systems, they can restore cellular energy supply and attenuate oxidative stress, thereby improving metabolic function, synaptic activity, and neural repair. This minireview summarizes recent advances in micro-/nanorobot applications for drug delivery, barrier penetration, stem-cell differentiation, and metabolic regulation. It explores their potential roles in improving neuronal function, limiting pathological protein aggregation, and facilitating neural network reconstruction. Also, clinical translation faces significant challenges, including safety evaluation, large-scale manufacturing, and regulatory compliance. A therapeutic framework centered on micro-/nanorobot-mediated metabolic regulation may provide a novel and effective approach for treating NDs.