Stereoselective Targeting with Chiral Nanomaterials: A Strategy for Precision Therapy in Neurodegenerative Diseases.

Abstract

The challenge in treating neurodegenerative diseases (NDs) lies in the complexity of their pathological mechanisms. Strategies capable of synergistically regulating multiple pathological features are crucial for treating NDs. Chiral nanomaterials (CNMs), including chiral nanoparticles (CNPs) and chiral nanoassemblies (CAMs), offer a unique platform for achieving such precise multitarget regulation because of their stereoselective interactions. Strategies for synthesizing CNMs are outlined in this review, and an in-depth analysis of their core biological mechanisms for treating NDs-inhibiting and clearing pathological proteins, enhancing synaptic plasticity, alleviating neuroinflammation, selectively eliminating senescent cells and promoting the differentiation of neural stem cells-is provided. Optimization of these functions through internal chiral design and external physical field modulation is explored. Finally, we propose forward-looking concepts such as "stage-optimized chiral nanomedicines" and "intelligently responsive chiral nanomaterials" to provide guidance for next-generation precision nanomedicine for NDs. STATEMENT OF SIGNIFICANCE: The key challenge in treating neurodegenerative diseases (NDs) lies in the precise identification and coordinated regulation of multi-target pathological processes. In recent years, chiral nanomaterials (CNMs), including chiral nanoparticles (CNPs) and chiral nanoassemblies (CAMs), have emerged as innovative tools for NDs intervention owing to their unique stereoselective recognition capabilities. This review systematically categorizes CNMs and their synthesis strategies, and focuses on elucidating their core biological mechanisms, including the inhibition and clearance of pathological proteins, enhancement of synaptic plasticity, alleviation of neuroinflammation, selective elimination of senescent cells, and promotion of neural stem cell differentiation. Furthermore, strategies to optimize their functionality through internal chiral structure design and external physical field modulation are explored. Collectively, this review aims to systematically elucidate the biological mechanisms and material properties of CNMs in NDs therapy, providing a theoretical foundation and guidance for the rational design and construction of next-generation neurorepair materials.