Flores-Prieto David E, Stabenfeldt Sarah E
School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States of America.
J Neural Eng. 2024 Dec 20;21(6). doi: 10.1088/1741-2552/ad995b.
Nanoparticle (NP)-based drug delivery systems hold immense potential for targeted therapy and diagnosis of neurological disorders, overcoming the limitations of conventional treatment modalities. This review explores the design considerations and functionalization strategies of NPs for precise targeting of the brain and central nervous system. This review discusses the challenges associated with drug delivery to the brain, including the blood-brain barrier and the complex heterogeneity of traumatic brain injury. We also examine the physicochemical properties of NPs, emphasizing the role of size, shape, and surface characteristics in their interactions with biological barriers and cellular uptake mechanisms. The review concludes by exploring the options of targeting ligands designed to augment NP affinity and retention to specific brain regions or cell types. Various targeting ligands are discussed for their ability to mimic receptor-ligand interaction, and brain-specific extracellular matrix components. Strategies to mimic viral mechanisms to increase uptake are discussed. Finally, the emergence of antibody, antibody fragments, and antibody mimicking peptides are discussed as promising targeting strategies. By integrating insights from these scientific fields, this review provides an understanding of NP-based targeting strategies for personalized medicine approaches to neurological disorders. The design considerations discussed here pave the way for the development of NP platforms with enhanced therapeutic efficacy and minimized off-target effects, ultimately advancing the field of neural engineering.
基于纳米颗粒（NP）的药物递送系统在神经疾病的靶向治疗和诊断方面具有巨大潜力，克服了传统治疗方式的局限性。本综述探讨了用于精确靶向大脑和中枢神经系统的纳米颗粒的设计考量和功能化策略。本综述讨论了与药物递送至大脑相关的挑战，包括血脑屏障和创伤性脑损伤的复杂异质性。我们还研究了纳米颗粒的物理化学性质，强调了尺寸、形状和表面特性在其与生物屏障相互作用以及细胞摄取机制中的作用。综述通过探讨旨在增强纳米颗粒对特定脑区或细胞类型的亲和力和滞留性的靶向配体选项来得出结论。讨论了各种靶向配体模拟受体 - 配体相互作用的能力以及脑特异性细胞外基质成分。还讨论了模拟病毒机制以增加摄取的策略。最后，讨论了抗体、抗体片段和抗体模拟肽作为有前景的靶向策略的出现。通过整合这些科学领域的见解，本综述提供了对基于纳米颗粒的靶向策略的理解，用于神经疾病的个性化医学方法。这里讨论的设计考量为开发具有更高治疗效果和最小脱靶效应的纳米颗粒平台铺平了道路，最终推动神经工程领域的发展。
