Stimuli-responsive nanoplatforms for central nervous system disorders: integrating delivery, modulation, and imaging

Abstract

Stimuli-responsive nanoplatforms have been reforming the landscape of central nervous system (CNS) therapeutics by successfully crossing the blood–brain barrier to allow spatiotemporal control over therapeutic activation, while simultaneously providing measurable imaging readouts for real-time monitoring. This review presents the rational design of nanoplatforms responsive to key endogenous cues, especially redox, pH and enzymatic signals, and discusses the therapeutic effects of exogenous physical stimuli, including light, ultrasound, magnetic and electrical fields, operated via real-time feedback. Beyond passive drug delivery, these integrated systems are endowed with the capacity to actively sense the localized microenvironment and utilize specific molecular signals for structural imaging, thereby enabling clinicians to personalize both drug dosimetry and stimulation timing for optimized outputs. Finally, we discuss the practical steps toward clinical translation by analyzing current trials and regulatory hurdles, and highlight how artificial intelligence can predict structure–function relationships and improve imaging clarity. When paired with scalable manufacturing, these tools are expected to promote the translation of brain-adaptive designs into viable clinical therapies.