Stimuli-responsive nanoscale drug delivery system for epilepsy theranostics

Epilepsy is a common neurological disease characterized by distinct pathological changes in the epileptogenic zone. Antiseizure drugs (ASDs) are widely used as the primary treatment for epilepsy. To improve the efficiency of ASDs medication, stimuli-responsive nanoscale drug delivery systems (nanoDDSs), triggered by either endogenous or exogenous factors, have been developed and been considered as a noninvasive and spatialtemporal approach to epilepsy theranostics. In this review, we introduce the pathological variations observed in epileptic lesions such as dysregulated neurotransmitter systems, disrupted ion homeostasis, and dynamic inflammatory cytokine networks. Furthermore, we summarize the recent advances in functional nano-assemblies that could be activated by endogenous stimuli of pathological alterations or exogenous stimuli such as electricity, light, and other interventions. Finally, we discuss the remaining challenges and prospect the insight into perspective of future development in this field. In summary, this review aims to highlight the potential of stimuliresponsive nanoDDSs as precise, controllable and efficient strategies for addressing unresolved issues in epilepsy theranostics. Statement of significance: This review summarizes recent progress in pathological changes such as dysregulated neurotransmitter system, disrupted ion homeostasis and dynamic inflammatory cytokine network, and emphasizes endogenous/exogenous stimuli-responsive nanoscale platforms including neurotransmitter-, ion-, and other stimuli-responsive nanoDDSs, providing the prospects of smart nanoDDSs applications and discussing the challenges to offer generalized guideline for further development of epilepsy theranostics.