Smart micro/nanorobots for drug delivery in the brain

Pharmacotherapy is the core approach for treating various brain diseases. However, the intricate anatomical structure and the blood–brain barrier (BBB) of the brain present challenges for intracerebral drug delivery and therapeutic efficacy. Although systemic administration and surgical interventions can alleviate symptoms, they are limited by low therapeutic effects and potential adverse side effects. Moreover, due to their complex pathogenesis, insidious development, and deep-seated lesions, brain diseases are difficult to diagnose accurately. To address these challenges, there is an urgent need to develop intelligent nanocarriers that can efficiently load drugs and penetrate the BBB for precise therapy of brain diseases. In this connection, micro/nanorobots (MNRs) are multifunctional drug carriers at the micro-nano scale, which possess exceptional penetration and targeting capabilities. Employing externally powered propulsion or chemical self-propulsion, MNRs can navigate in the brain and cross the BBB. This review comprehensively summarizes the recent advances and future outlook of smart MNR drug delivery systems for brain disease treatment. It covers broad topics from nanocarriers to active smart MNRs. Furthermore, it elucidates the therapeutic mechanisms of these smart MNR drug delivery systems in brain diseases based on pathogenesis and pathology. Our aim is to provide a reference for designing and developing novel smart MNRs for drug delivery in the brain, paving the way for their clinical applications in treating brain diseases.