Shuhan Liu,1– 3 Haisong Li,4 Shiwen Xi,1,2 Yuning Zhang,1,2,* Tianmeng Sun1,2,5,6,* 

1Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, People’s Republic of China; 2National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, People’s Republic of China; 3Cancer Center, The First Hospital, Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Neurosurgery, The First Hospital, Jilin University, Changchun, Jilin, People’s Republic of China; 5International Center of Future Science, Jilin University, Changchun, People’s Republic of China; 6State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Tianmeng Sun; Yuning Zhang, The First Hospital of Jilin University, 71 Xinmin St, Changchun, Jilin, People’s Republic of China, Email tsun41@jlu.edu.cn; zhangyuning@jlu.edu.cn

Abstract: Given the complexity of the central nervous system (CNS) and the diversity of neurological conditions, the increasing prevalence of neurological disorders poses a significant challenge to modern medicine. These disorders, ranging from neurodegenerative diseases to psychiatric conditions, not only impact individuals but also place a substantial burden on healthcare systems and society. A major obstacle in treating these conditions is the blood-brain barrier (BBB), which restricts the passage of therapeutic agents to the brain. Nanotechnology, particularly the use of nanoparticles (NPs), offers a promising solution to this challenge. NPs possess unique properties such as small size, large surface area, and modifiable surface characteristics, enabling them to cross the BBB and deliver drugs directly to the affected brain regions. This review focuses on the application of NPs in gene therapy and enzyme replacement therapy (ERT) for neurological disorders. Gene therapy involves altering or manipulating gene expression and can be enhanced by NPs designed to carry various genetic materials. Similarly, NPs can improve the efficacy of ERT for lysosomal storage disorders (LSDs) by facilitating enzyme delivery to the brain, overcoming issues like immunogenicity and instability. Taken together, this review explores the potential of NPs in revolutionizing treatment options for neurological disorders, highlighting their advantages and the future directions in this rapidly evolving field.

Keywords: central nervous system, nanoparticle, gene therapy, enzyme replacement therapy, lysosomal storage disorders, neurological disorders