A comprehensive review published in Chemical Society Reviews highlights how stimuli-responsive nanoplatforms are reshaping the future of central nervous system (CNS) therapeutics. The work integrates targeted delivery, neuromodulation, and real-time imaging into adaptive “brain-responsive” treatment systems.

The review, titled “Stimuli-Responsive Nanoplatforms for Central Nervous System Disorders: Integrating Delivery, Modulation, and Imaging,” was led by Prof. Jianlin SHI and Prof. Han LIN from the Shanghai Institute of Ceramics, Chinese Academy of Sciences (SICCAS).

Neurological disorders—including stroke, spinal cord injury, glioblastoma, Alzheimer's disease, and Parkinson's disease—remain among the leading causes of disability worldwide. Effective treatment is extremely challenging due to the blood-brain barrier (BBB), the dynamic complexity of CNS lesions, and the lack of technologies capable of precisely regulating therapeutic activity in space and time.

Unlike conventional nanocarriers that function primarily as passive delivery vehicles, the intelligent systems reviewed here actively sense pathological microenvironments and respond to external physical fields. They integrate lesion recognition, controlled therapeutic activation, and imaging feedback into a unified framework.

The review systematically covers both endogenous biochemical triggers and exogenous physical modulation strategies. Endogenous cues—including reactive oxygen species (ROS), pH changes, and dysregulated enzyme activities—serve as programmable signals for lesion-specific drug release and immunomodulation. Exogenous stimuli, such as light, ultrasound, magnetic fields, and electrical modulation, provide precise spatiotemporal control over neuromodulation, BBB permeability, and therapeutic activation. Focused ultrasound is highlighted as a particularly promising translational strategy.

The review further discusses the integration of multimodal imaging technologies, including MRI, PET, photoacoustic imaging, and NIR-II imaging, to establish imaging-guided closed-loop therapeutic systems. AI-assisted approaches are also explored for optimizing BBB penetration, structure-function prediction, and therapeutic design.

Finally, current clinical translation efforts and key challenges—including safety standardization, dosimetry, scalable manufacturing, and regulatory complexity—are comprehensively analyzed. According to the authors, future CNS nanomedicine will increasingly rely on the integration of responsive materials, multimodal imaging, AI-guided optimization, and clinically compatible stimulation technologies. Such adaptive systems may ultimately enable personalized, real-time therapeutic regulation for complex neurological disorders.

This work provides a comprehensive framework for researchers across chemistry, materials science, bioengineering, and clinical neuroscience, offering practical guidance for translating intelligent nanotherapeutics from laboratory research toward clinical applications.

Schematic of stimuli-responsive nanoplatforms for brain-adaptive CNS therapy. Nanomaterials detect endogenous lesion cues. Specific triggers include ROS, acidic pH, enzymatic activity, and ionic imbalances. Simultaneously, the systems respond to exogenous fields. Key modalities include light, magnetic, ultrasound, and electrical stimulation. This dual responsiveness integrates BBB crossing with precise localization. Ultimately, the platforms enable on-demand drug delivery, neuromodulation, and real-time imaging feedback.

Contact: LIN Han

Shanghai Institute of Ceramics Chinese Academy of Sciences

E-mail: linhan@mail.sic.ac.cn

Published online: May 14, 2026